[Clinical significance of galactosyltransferase associated with tumor (GAT), a new tumor marker for ovarian cancer--with special reference to the discrimination between ovarian cancer and endometriosis].

We examined GAT, a newly developed tumor marker, in serum samples collected from 1,503 females in six institutions: 387 healthy females, 1,052 patients with gynecological diseases including 311 ovarian cancers, and 64 with nongynecological diseases. Based on the mean value + 2 SD for the healthy females, the cut-off value was set at 16 U/ml. The positive rate of GAT was 2.6% for the healthy females, 7.1% for patients with benign ovarian tumor, 5.6% for those with endometriosis, 47.9% for those with ovarian cancers, 9.3% for those with cervical cancer, and 13.3% for those with endometrial cancer. The false-positive rate of GAT for endometriosis was very low compared with that of the other markers such as CA 125, CA 602, CA 54/61, CA 72-4, STN, SLX examined in this study. The positive predictive value between ovarian cancer and endometriosis was the highest with GAT among the evaluated markers. In the cases in which the CA 125 (CA 602) value is relatively low, discrimination between ovarian cancer and endometriosis is difficult, because these cases include many patients with endometriosis. GAT showed the highest positive predictive value in such cases, so GAT proved to play a complementary role with CA 125 (CA 602). Combination assay with GAT and CA 54/61/CA 72-4/STN or SLX showed higher diagnostic efficiency between ovarian cancer and endometriosis. These results suggest the usefulness of GAT for discrimination between ovarian cancer and endometriosis.

[Development and clinical research of computer aided multivariate pattern analysis system (CAMPAS) OV-1 for diagnosis of ovarian carcinoma].

A computer aided multivariate pattern analysis system (CAMPAS) OV-1, which consisted of 10 discriminant functions based on eight tumor markers including CA125, IAP, TPA, LDH, CRP, CEA, amylase and alkaline phosphatase was developed to effectively diagnose patients with epithelial ovarian carcinoma. One hundred twenty-two patents with epithelial ovarian carcinoma and 215 patients with benign ovarian tumors were examined by using CAMPAS OV-1 retrospectively or prospectively. The clinical significance of CAMPAS OV-1 was compared with CA125 alone, and with a combined assay employing the eight tumor markers used in CAMPAS OV-1. The following results were obtained. 1. When CAMPAS OV-1 was applied to patients in which the value for each tumor marker was used to make the discriminant functions, the sensitivity, specificity and accuracy were 84.5%, 97.5% and 91.3%, respectively. The accuracy of CAMPAS OV-1 (91.3%) was significantly better than those of CA125 (80.0%) and combined assay (74.0%) [p < 0.001]. CAMPAS OV-1 showed relatively better sensitivity (63.3%) than CA125 (50.0%) in patients with stage I disease. Also CAMPAS OV-1 showed relatively better sensitivity (85.7%) than both CA125 (64.3%) and combined assay (78.6%) in patients with mucinous type tumors. Furthermore, the specificity of CAMPAS OV-1 (94.4%) was significantly better than those of CA125 (66.7%) and combined assay (55.6%) in patients with endometrial cysts [p < 0.05]. 2. When CAMPAS OV-1 was applied to the patients prospectively, whose values for each tumor marker were not used to make the discriminant functions, the sensitivity, specificity and accuracy were 88.2%, 83.8% and 85.0% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian mucinous cystadenocarcinoma producing alpha-fetoprotein. A case report.

A 62-year-old woman with a complaint of abdominal distention underwent surgery to remove a tumor in her left ovary. The serum alpha-fetoprotein (AFP) level was 4,130 ng/ml. Histologically, the tumor was diagnosed as a mucinous cystadenocarcinoma with a small area of solid proliferation of tumor cells. The cells of the latter part were shown immunohistochemically to possess AFP. We suppose that a part of the mucinous cystadenocarcinoma dedifferentiates and produces AFP.

RGD-containing peptides inhibit experimental peritoneal seeding of human ovarian cancer cells.

A synthetic peptide containing the RGD (Arg-Gly-Asp) sequence is known to inhibit the attachment between cells and the extracellular matrix (ECM) in vitro, and also inhibit experimental pulmonary metastasis of murine melanoma cells in vivo. Prevention of peritoneal seeding by RGD-containing peptides has never previously been discussed. In this study, the inhibition of peritoneal seeding by RGD-containing peptides is examined, using the in vivo experimental peritoneal seeding model with human ovarian cancer cells (JHOC-1). Intraperitoneal (i.p.) inoculation of nude mice with JHOC-1 cells soon resulted in peritoneal seeding in all of the mice. Most of them expired within 4 to 80 weeks, and none survived for as long as 10 weeks. GRGDS (Gly-Arg-Gly-Asp-Ser) sequenced synthetic peptides were administered by i.p. injection after tumor cell inoculation following some regimens, and the changes in body weight and the periods of survival of the peptides-treated and untreated mice were observed. Intraperitoneal administration of 2mg/mouse of GRGDS peptides (every 8 hours, for 4 days, beginning just after tumor cell inoculation) significantly prolonged the survival periods of the tumor implanted mice. In this study, RGD-containing peptides were found to be able to prevent in vivo experimental peritoneal seeding by continual i.p. administration. This might indicate that RGD and integrins plays a critical role in peritoneal seeding as well as in hematogeneous metastasis.

[Treatment and overview for the improvement of prognosis in ovarian cancer].

The current treatment for ovarian cancer introduced the improvement of survival rate by the chemotherapy based on cisplatin and maximum debulking surgery. The prognosis of ovarian cancer is affected by various kinds of factor as age, ps, stage, histology, histological grading and the volume of residual tumor. By our analysis it was shown whether tumor diameter is less than 2 cm or not was critical point. On the other hand, dose intensity of cisplatin is also important. We could show the improvement of survival rate of advanced cases by the treatment of maximum debulking surgery and high intensity of cisplatin.

Serum levels and biochemical characteristics of human ovarian carcinoma-associated antigen defined by murine monoclonal antibody, CF511.

The murine monoclonal antibody (Mab) against human common epithelial ovarian carcinoma, CF511, was generated by immunising mice with human fetal tissue extract from early first trimester, followed by booster injection of an ovarian cancer cell line. Mab CF511 recognised the 600 kDa sialylated glycoprotein as different from previously known tumour associated-marker antigens. Distribution of the Mab CF511-recognised antigen (CF511 antigen) in various tissues and sera was investigated. In immunohistochemical analysis, Mab CF511 reacted strongly with tumour cells of ovarian serous, clear cell, endometrioid and undifferentiated carcinoma and partially with those of mucinous carcinoma. Mab CF511 also reacted with breast carcinoma as well as lung carcinoma. In normal tissues, Mab CF511 cross-reacted with only five tissues, namely lung, breast, thyroid gland, fallopian tube and uterus. Serum levels of CF511 antigen were tested by ELISA inhibition using Mab CF511. This assay showed the circulating CF511 antigen levels to be elevated in 25 of 36 sera from patients with various clinical stages of common epithelial ovarian carcinoma compared to three of 47 and three of 111 sera from patients with other benign gynaecological diseases, including ovarian cysts, uterine fibroids with or without endometriosis and normal healthy subjects, respectively. For the relation between antigen levels and clinical stages of common epithelial ovarian carcinoma, greater than 34.0% ELISA inhibition was detected in 100% of patients with advanced stages (FIGO III and IV) compared with in 35.3% with early stages (FIGO I and II) patients. While patients with breast carcinoma (100%) and lung carcinoma (100%) also had elevated circulating CF511 antigen levels, patients with hepatoma, colorectal carcinoma and gastric carcinoma had no detectable elevation of antigen. Although the test showed a high degree of specificity, the detection of an elevated CF511 antigen level would not be so helpful in distinguishing patients with ovarian carcinoma from those with either breast carcinoma or lung carcinoma. These data suggest that CF511 antigen is a useful new ovarian tumour marker for diagnosis and management of the disease.

Circulating tumor-associated antigen detected by the murine monoclonal antibody CF511 in human epithelial ovarian carcinoma.

The murine monoclonal antibody (Mab) to human common epithelial ovarian carcinoma, CF511, was generated by immunizing mice with human fetal tissue extract followed by a booster injection of ovarian cancer cells. Mab CF511 recognized the 600KD sialylated glycoprotein as being different from previously known tumor-associated marker antigens. Mab CF511 reacted with common epithelial ovarian carcinomas, and also reacted with breast and lung carcinoma. In normal tissue, Mab CF511 cross-reacted with the lungs, breast, thyroid, fallopian tubes and uterine endometrium. CF511 antigen was increased in sera of approximately 70% of the patients with common epithelial ovarian carcinoma. CF511 antigen levels in sera from patients with ovarian carcinoma corresponded to the clinical course. CF511 antigen was increased in only 3% of the 47 collections of sera from patients with benign gynecological diseases. These data suggests that CF511 antigen is a useful new ovarian tumor marker for the diagnosis and management of the disease.

[Prognostic study of ovarian clear cell carcinoma].

Prognostic studies were performed on 17 cases with clear cell carcinoma of the ovary. The results are follows: 1) The average age was 45.9 years and ranging from 35 to 57 years. 2) Regarding the FIGO clinical stage, all of 5 patients with stage I and 3 of 5 with stage II survived over 2 years, while all of patients with stage III and 2 with stage IV were dead within 2 years. 3) Of 9 patients who had complete resection for primary operation, 8 (89%) survived over 2 years. All of 8 patients who had incomplete resection were dead within 2 years. 4) All cases had been received various chemotherapy; CQ + 5-FU (n = 5), CPM + ADM + CDDP + 5-FU (n = 7), 5-FU + CPM + MMC (n = 2), CDDP (n = 1), CDDP + MMC + 5-FU (n = 1), MCNU + VCR + 5-FU (n = 1), but none of them improved the prognosis of this histological type. 5) With or without administration of CDDP, there was no significant difference in the prognosis. These results suggest that early diagnosis of disease, curative surgical resection and selection of effective chemotherapeutic agents are important things to improve prognosis of clear cell carcinoma of the ovary.

[Experimental study of the mechanism of peritoneal dissemination--with special reference to scanning electron microscopic observations].

Most malignant ovarian tumors metastasize by peritoneal dissemination and have a poor prognosis. Few studies have been made to determine how free ovarian tumor cells act on the peritoneum and become lodged and proliferate therein and much still remains to be clarified concerning this issue. In the present study, we transplanted 2 X 10(6) cells of JOHYL-1 strain established from an atypical dysgerminoma into the peritoneal cavity of nude mice observed serially morphological changes in the peritoneum resulting from tumor cell dissemination both by light microscopy and SEM. The findings thus obtained may be summarized as follows: From 5 to 7 days after intraperitoneal transplantation of tumor cells, mesothelial cells of the peritoneum began to swell, with the intercellular boundaries becoming distinct. Microvilli of the mesothelial cells increased in number, forming a mesh-like structure, and in some places were found to be in direct contact with a tumor cell. From 10 days after tumor cell transplantation onwards the mesothelium showed enlarged intercellular spaces in some places, and at these sites tumor cells were seen to have adhered. On other sites mesothelial cells were being partially lost. From 11 days after being transplanted, the tumor cells started proliferating and infiltrating in the muscle layer. Concerning the site of tumor cell implantation, evidence was obtained showing that tumor cells adhered to intercellular spaces of mesothelial cells, and/or in defects formed on connective tissue by a loss of mesothelial cells. The study thus demonstrated a salient usefulness of the JOHYL-1 ascites type cell line, with a reliably great capacity for growth in vivo, as an experimental model for the study of peritoneal dissemination of tumor cells.

[Experimental chemotherapy of germ cell tumor heterotransplanted to nude mice].

While the treatment of ovarian cancer has made remarkable progress in recent years, the chemotherapy of ovarian germ cell tumor has not as yet been fully established and remains to be improved. We investigated the effectiveness of a single-agent therapy with Vincristine (VCR), Actinomycin D (ACD), and Cyclophosphamide (CPM) against a human undifferentiated dysgerminoma's cell line (JOHYL-1) with the following results. The ratio of the number of viable cells to the total cell population treated for JOHYL-1 cells of ascitic type was 70% with VCR, 58% with CPM and 25% with ACD; hence the efficacy on this malignant cell line was the greatest with ACD followed by VCR and CPM in that descending order. Notably with CPM, a striking antitumor effect was observed from 48 to 24 hours after treatment. The L.I. attained a peak at 24, 18 and 30 hours, respectively, after treatment with VCR, ACD and CPM. The M.I. was as high as a little more than 6% at 36 hours after treatment with VCR. There also was noted a shift in the cell cycle with any of the test drugs. Morphological changes observed in the cell were most obvious with ACD followed in order by VCR and CPM. LDH & isozyme pattern: In these respects there were no striking differences among the three drugs, even though the total enzyme activity was somewhat higher with VCR.(ABSTRACT TRUNCATED AT 250 WORDS)

[Biochemical activity in peritoneal effusion of ovarian malignancy].

This study was provided biochemical findings on ascitic fluid following the treatment of patients with ovarian tumors. The results were as follows: LDH and LDH isozyme. The ascitic fluid from patients with germ cell tumors showed an LDH1 value of 38.8% with an H/M ratio of 2.82, which were significantly higher than those found in the benign tumor group (LDH1, 15.2%: H/M ratio, 1.05). In cases of adenocarcinomas, the LDH5 value was 27.2%, compared to 15.7% in cases of benign tumors. Of 28 patients with adenocarcinoma, 15 patients (53.6%) were positive for this elevation. The decline in total LDH activity and elevation of H/M ratio were observed as a general tendency in patients satisfactorily responding to treatment. ALP and ALP isozyme. The malignant tumor group displayed higher values for both total ALP activity and HSAP in ascitic fluid, as compared with the benign tumor group. In the malignant tumor group, alpha 2 and alpha 2-beta regions were prominent in the isozyme pattern and the isozymes of the same regions remained even after inactivation by heat. The total activity decreased significantly in the responders to treatment. TP, alpha 1-AT, alpha 1-AG, alpha 2-M and IgG. The ascitic fluid levels of alpha 1-AT, alpha 2-M and IgG did not significantly differ among the group of patients with germ cell tumors, the group of patients with ovarian gonadal stroma and the group of patients with benign tumors. In the adenocarcinoma group the alpha 1-AT and alpha 2-M levels were higher than those in the benign tumor group. The ascitic fluid alpha 1-AG level and alpha 1-AG/TP ratio were elevated in tumors of germ cell origin and in adenocarcinomas; they tended to correlate with the degree of malignancy of the tumor. The results of the present study suggest that simultaneous measurement of the ascitic fluid levels of LDH isozymes, ALP isozymes, alpha 1-AG, alpha 1-AT, alpha 2-M and IgG may play a potential adjunctive role in providing information for diagnostic differentiation between benign and malignancy, estimation of the histologic type and extent of neoplastic growth, evaluation of the therapeutic response and prediction of the clinical progress.

[Clinical significance of new tumor marker CA 125 in gynecological cancer--particularly usefulness in diagnosis of ovarian cancer].

A concentration in sera of a new antigen CA125 related to cancer of the ovary was measured by radioimmunoassay which used a monoclonal antibody, and its usefulness as a tumor marker in the diagnosis of cancer of the ovary was investigated. The mean values for CA125 in sera of healthy controls (80 females) were 14.2 +/- 12.2 U/ml. Mean values for CA125 in sera of various patients were 29.0 +/- 39.6 for myoma uteri (30 cases), 26.7 +/- 30.1 for benign ovarian tumors (10 cases), 64.4 +/- 146.2 for cervical carcinoma (14 cases), and 31.5 +/- 19.8 for endometrial carcinoma (6 cases), whereas the mean values for ovarian cancers (23 cases) were as high as 311.3 +/- 250.4. On the other hand, positive rates for CA125, when the cut-off value was set to 65 U/ml, were 1.3% for healthy controls (1 out of 80 cases), 10.0% for myoma uteri (3 out of 30 cases), 10.0% for benign ovarian tumors (1 out of 10 cases), 14.3% for cervical carcinoma (2 out of 14 cases), and 16.7% for endometrial carcinoma (1 out of 6 cases), whereas the positive rate for ovarian cancers was 78.3% (18 out of 23 cases). Especially for serous cystadenocarcinoma, the positive rate was 100% (10 out of 10 cases). From the above, the measurement of CA125 in sera was considered to be significant in the diagnosis of ovarian cancer.