Yoshio Okudaira

Immunosuppressive acidic protein in patients with ovarian cancer.

Serum immunosuppressive acidic protein (IAP) was determined in 63 patients with ovarian tumors (33 benign and 30 malignant) and 79 healthy female controls, and was examined as a marker for ovarian cancer in comparison with carcinoembryonic antigen (CEA). The mean value of serum IAP in patients with ovarian cancer (1085 ± 474 μg/ml) was statistically higher than those of both benign tumors (394 ± 93 μg/ml) and controls (298 ± 92 μg/ml). Elevated levels of IAP and CEA were found in 93.3% and 30.0% of patients with ovarian cancer, respectively. There were three false‐positive cases with IAP and two with CEA. Elevation of IAP was recognized in all cancer patients in Stage I, whereas 33.3% of these patients showed elevated CEA. The occurrence of elevated serum IAP was not affected by tumor histologic features. Serial IAP determination appeared to provide a useful follow‐up marker in patients in whom CEA was low in value. The measurement of serum IAP is highly recommended as an addition to the conventional diagnostic methods. Cancer 52:2081‐2085, 1983.

Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study.

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group.The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p=0.074; generalized Kruskal-Wallis, p=0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Krukal-Wallis, p=0.045). No side effects attributable to SPG were recorded.The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.

Immunotherapy of tumor-bearing mice utilizing virus help.

SummaryUtilizing vaccinia virus (VV), a tumor-specific immunotherapy model was established in which a growing tumor regressed. C3H/HeN mice were primed with VV after low dose irradiation to generate amplified VV-reactive T cell activities. Then 4 weeks later, the mice were inoculated i. d. with syngeneic MH134 hepatoma cells, and 6 days after the tumor cell inoculation, live VV was injected into the tumor mass 3 times at 2-day intervals. Of 10 mice which had received VV priming and subsequent VV injection into the tumor mass, 8 exhibited complete tumor regression. On the contrary, mice which had received only intratumoral VV injection without VV priming failed to exhibit appreciable tumor regression. Mice whose tumor had completely regressed following the VV immunotherapy were shown to have acquired systemic antitumor immunity, which was confirmed by a challenge with syngeneic tumor cells after immunotherapy. In vitro analysis of these immune mice revealed that potent tumor-specific antibody responses were preferentially induced, but with no detectable antitumor cytotoxic T lymphocyte (CTL) responses. Such a potent tumor-specific immunity was not observed in mice which had received intratumoral VV injection in the absence of VV priming. Thus, the results clearly indicate that tumor regression was accompanied by the concurrent generation of a potent tumor-specific immunity, suggesting that cellular cooperation between VV-reactive T cells and tumor-specific effector cells might be functioning in this VV immunotherapy protocol. Therefore, the present model provides an effective maneuver for tumor-specific immunotherapy. This system is, in principle, applicable to the human situation.

Cisplatin, vinblastine, and bleomycin therapy of yolk sac (endodermal sinus) tumor of the ovary

Five patients with yolk sac (endodermal sinus) tumor of the ovary were treated with cisplatin, vinblastine, and bleomycin combination therapy (PVB). Four of five achieved a complete remission and remain free from disease 24 to 53 months from start of PVB therapy. One patient did not respond well to PVB and died 11 months after start of PVB therapy. One patient who was treated with PVB after unilateral salpingo-oophorectomy has delivered a normal term infant. Serum alpha-fetoprotein levels were monitored in all patients during and after therapy. Serum alpha-fetoprotein was correlated with clinical course.

Management of patients with gynecologic cancer by serum sialic acid determination

Abstract With an enzymatic technique, serum sialic acid (SA) levels were determined in patients with gynecologic tumors. Since the SA level for healthy females was 57.4 ± 7.3 mg/dl, we set the upper normal limit of this parameter at 72 mg/dl. The SA level became larger in ascending order of uterine myoma, benign ovarian tumor, cervical cancer, corpus cancer, and ovarian cancer. The SA level proved to be significantly higher in cancer patients showing poor prognosis than in those having good prognosis irrespective of the category of therapy and it reflected well the clinical course of cancer patients. In patients who receive a combination therapy and need to be followed up for a long term, complete follow-up is sometimes impossible with tumor-derived markers alone. Even in such cases, the sialic acid level will work as a useful follow-up marker because it is nonspecific to histologic types of cancer.

Human gynecologic cancers heterotransplanted into athymic nude rats

Abstract The serial transplants of human ovarian and endometrial tumors in nude mice were transplanted into nude rats. The transplants consisted of three lines of yolk sac tumors, designated as YST-1, YST-2, and YST-3 and two lines of endometrial adenocarcinoma, AD-30 and AD-35. The transplanted tumors grew much larger in nude rats than in nude mice, reaching more than 150 g in weight. The overall grafting success rate of these tumors was about 70% in nude rats whereas it had been almost 100% in nude mice. The histology of the transplanted tumor in nude rats was similar to that of the same tumor in nude mice. YST-1, YST-2, and YST-3 tumors produced the marker α-fetoprotein (AFP). Thus the transplanted tumors in nude rats seemed to preserve the characteristics of the original tumors. The usefulness of the nude rat as a tool for studying the efficacy of treatments on human malignant tumors is discussed.

Establishment of a new ovarian tumor line in nude mice and its application to treatment of the donor patient

A new line of the human ovarian tumor (poorly differentiated adenocarcinoma), designated OVA-2, has been established by heterotransplantation of the original tumor into athymic nude mice. The donor patient, a 38-year-old woman with stage IV disease, was treated with cis-diamminedichloroplatinum II, Adriamycin, 5-fluorouracil, and VM-26, which were selected in consideration of the results, obtained by experimental chemotherapy of this heterotransplanted tumor. She achieved a complete remission and is alive 15 months after diagnosis. Usefulness of the human tumor-nude mouse system in chemotherapy is reemphasized.

Diagnostic significance of pregnancy-associated α2-glycoprotein in patients with ovarian cancer

Abstract Pregnancy-associated α 2 -glycoprotein (α 2 -PAG) levels were measured in several kinds of samples by a modification of Laurells electroimmunoassay using a rabbit anti- α 2 -PAG serum. Samples were sera obtained from healthy females (46 cases), patients with benign ovarian tumors (8 cases), patients with ovarian cancers (18 cases), nude mice bearing heterotransplanted human ovarian cancers (4 cases), and ascites and urine of cancer patients. Serum α 2 -PAG levels in patients with benign ovarian tumors were 3.8 ± 3.2 U/μl and almost the same as those of controls (2.6 ± 3.0 U/μl). However, serum α 2 -PAG levels were higher in patients with ovarian cancers (12.0 ± 3.7 U/μl). α 2 -PAG was scarcely detected in ascites or urine obtained from cancer patients, and was not detected in sera of tumor-bearing nude mice, despite the high levels of α 2 -PAG in those of original patients. The reliability of α 2 -PAG as a tumor-associated marker in patients with ovarian cancer was reinforced by the comparison of the positive rates of the two parameters, α 2 -PAG and carcinoembryonic antigen (CEA).