Keisuke Sawai

Metastatic ovarian tumors: a review of 64 cases

OBJECTIVE The goal was to review cases of metastatic ovarian tumor with respect to their clinical features. METHODS Sixty-four patients with pathologically confirmed metastatic ovarian carcinoma, who were treated between 1978 and 2002 at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), were reviewed and the clinical features examined. RESULTS We found that metastatic tumors accounted for 21.1% (64/304) of malignant ovarian tumors. Of 64 metastatic ovarian tumors, 26 originated from gynecologic organs, and 38, from nongynecologic organs. Gynecologic primary sites were the uterine body (23%), uterine cervix (14%), and fallopian tube (3%). Eight of nine cervical cancers with ovarian metastases were adenocarcinomas. Adenocarcinoma of the uterine cervix metastasized to the ovaries more frequently than squamous cell carcinoma (5.6% vs 0.1%, respectively; P < 0.01). Among 38 cases of metastatic ovarian tumors from nongynecologic organs, Krukenberg tumors, pathologically characterized by the presence of typical signet-ring cells, were found in 11 patients (29%). Most (8/11) had originated in the stomach. Half (19/38) were preoperatively diagnosed as metastases. The 5-year survival rate after resection of metastatic ovarian tumors from gynecologic organs was significantly higher than the rate after resection of such tumors from nongynecologic organs (47% vs 19%, respectively; P = 0.026). CONCLUSIONS Metastatic ovarian tumors are likely to be relatively common in Japan because of the high incidence of gastric cancer. In cases of pelvic tumor, metastatic ovarian tumor should always be included in the differential diagnoses. As the 5-year survival after resection of metastatic ovarian tumor is 19%, even for tumors from nongynecologic organs, it seems worthwhile to consider tumorectomy as the second cytoreduction.

Production of interleukin-6 by normal human trophoblast.

The placenta plays a number of important roles during pregnancy, some of which might be mediated by cytokines with multiple activities such as IL-6. Using an IL-6-dependent cell line, MH6o.BSF2, we showed that the placenta released IL-6 into the culture supernatant. Analysis of single-cell suspensions of placental cells determined the major source of IL-6 to be trophoblast. Using a mouse monoclonal antibody specific for IL-6 (alpha BSF2-I66), immuno-histochemical analysis of placental specimens demonstrated the localization of IL-6 only in the trophoblast layer. Additional immunocytochemical studies with single-cell suspensions of trophoblasts demonstrated the preferential presence of IL-6 molecules in syncytiotrophoblasts rather than cytotrophoblasts. The evidence that a high titer of IL-6 is produced spontaneously by syncytiotrophoblasts indicates that IL-6 may play immunological roles in fetomaternal interactions by means of IL-6-driven multiple immunoregulatory activities.

Elevated Nitric Oxide Concentration in the Seminal Plasma of Infertile Males: Nitric Oxide Inhibits Sperm Motility

PROBLEM: To evaluate the “effect of nitric oxide in the seminal plasma on sperm motility. METHOD: Seminal plasma concentrations of NO2—, a stable end product of nitric oxide, of 108 males of infertile couples and 15 proven fertile donors were measured and compared with spermatogram parameters. Motile sperm was incubated with a nitric oxide‐generating drug, sodium nitroprusside, for 6 hr in the absence or presence of oxyhemoglobin, an inhibitor of nitric oxide.

Detection of monocyte chemotactic and activating factor (MCAF) and interleukin (IL)-6 in human seminal plasma and effect of leukospermia on these cytokine levels

PROBLEM: To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin‐6 (IL‐6) are present in the seminal plasma, and whether these presence is modulated by leukospermia.

Maintenance of imprinting of the insulin-like growth factor II gene (IGF2) and the small nuclear ribonucleoprotein polypeptide N gene (SNRPN) in the human uterus and leiomyoma

The insulin-like growth factor II gene (IGF2) is thought to be involved in the growth of uterine smooth muscle tumors. We studied the allele-specific expression of IGF2 in 20 patients with uterine leiomyomas by analyzing restriction fragment length polymorphisms (RFLP), because IGF2 is a maternally imprinted gene and only the paternal allele is exclusively expressed in human somatic tissue. We also studied the allelic expression of the small nuclear ribonucleoprotein polypeptide N gene (SNRPN), which is reportedly maternally imprinted in humans, and compared the imprinting status with that of IGF2. Nine patients (45%) were heterozygous at the ApaI site of IGF2, nine (45%) were heterozygous at the possible AccII polymorphic site of SNRPN, and three (15%) showed polymorphism in both genes. The genomic DNA of 15 patients showed heterozygosity in either or both of these genes, and the mRNA of these was expressed monoallelically in myometrial tissues and leiomyomas of these patients. These results demonstrated that IGF2 and SNRPN imprinting is completely maintained in human uteri and leiomyomas and that increased expression of IGF2 is not due to biallelic expression.

Demonstration of functional immaturity of signal transduction pathways in human cord T cells

We examined the nature of cytoplasmic signal transduction pathways in cord blood T cells by stimulating them with tumor promoter (TPA) and calcium ionophore (A23187). Costimulation of T cells with TPA and A23187 induced optimal proliferative responses on Day 2 in cord T cells but on Day 4 in adult T cells. The maximal responses observed in cord T cells were much less than those of adult T cells, whereas the Con A-induced proliferative responses of these cells showed no significant differences. The reduced responses of cord T cells were due to their lower efficiency in activating the cellular events in T cell activation and proliferation phase, because cord T cells have significantly less ability than adult T cells to express IL-2 receptor as well as HLA-DR and produce IL-2 molecules, thereby inducing proliferation. These data show immature characteristics of intracellular signal transduction pathways in cord T cells, which are directly related with the functional immaturity of cord T cells.

Analysis of immunoregulatory activity of a choriocarcinoma-derived factor: specific suppression of proliferative process of cell-mediated immune responses including LAK cell generation

The immunosuppressive activity of a JEG-3 choriocarcinoma-derived factor in human IL-2-dependent T cell responses has been studied, together with its effect on IL-2-independent T cell responses induced by 10 nM TPA. The factor completely suppressed the IL-2-independent proliferative responses of T cells but failed to suppress antigenic expression of activation-associated CD 25 molecules. Further studies examined the effect of the factor on LAK cell generation induced by rIL-2. Recombinant IL-2-induced LAK cell proliferation was observed on Day 4 and Day 5, but not on Day 3. As the factor suppressed the responses of LAK cell proliferation, we tested whether it blocked the generation of Day 3, Day 4 and Day 5 LAK cells. The addition of the factor failed to suppress the generation of Day 3 LAK cells, while it partially suppressed the lytic activity of Day 4 LAK cells and completely suppressed that of Day 5 LAK cells. The data suggest the presence of a heterogeneous pattern for LAK cell generation; one without proliferation, but the other requiring proliferation, to acquire killer activity. Taken together with the evidence that the factor failed to suppress NK activity, the choriocarcinoma-derived factor suppressed only the proliferative events of immunocompetent cells, but inhibited neither their activation nor the differentiation events. This immunosuppressive factor might be involved in the prevention of host-mediated rejection of choriocarcinoma cells or maternal rejection of the fetus.