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At least 289 records · Page 16Linked to original sources
PubMed1983

Comparison of a rabbit heteroantiserum and a murine monoclonal antibody raised against a human epithelial ovarian carcinoma cell line.

An ovarian carcinoma cell line (OVCA 432) and a B-lymphocyte line (LAZ 446) were established from the same donor. A heteroantiserum (D-100) was prepared in rabbits against OVCA 432 and absorbed with LAZ 446, human AB erythrocytes, and the CX-1 colorectal cell line. After absorption, D-100 reacted by indirect immunofluorescence with six of six epithelial ovarian carcinoma cell lines and cryostat sections of 18 of 18 epithelial ovarian tumors but bound to zero of 12 nonovarian tumor cell lines. Despite a lack of reactivity with nonovarian tumor cell lines, D-100 reacted with epithelial components of normal ovary, fallopian tube, endometrium, endocervix, breast, colon, and epididymis. A murine monoclonal antibody (OC 133) was also raised against OVCA 432 and selected for lack of reactivity with the autologous B-lymphocyte line LAZ 446. OC 133 reacted with six of six ovarian carcinoma cell lines and cryostat sections of seven of 19 ovarian tumors, but it also reacted with five of five nonovarian tumor cell lines. Of 12 normal tissues examined, OC 133 reacted with endometrium and endocervix only. Whereas D-100 bound to serous, mucinous, endometrioid, and clear cell ovarian neoplasms, OC 133 bound only to serous tumors. In developing monoclonal reagents, cell lines may provide a useful source of antigen, but promising antibodies should be screened for reactivity with sections of normal and malignant human tissues.

Animals↗
PubMed1984

Monitoring human ovarian carcinoma with a combination of CA 125, CA 19-9, and carcinoembryonic antigen.

CA 125 and CA 19-9 are antigenic determinants associated with human epithelial ovarian carcinomas. Murine monoclonal antibodies have been raised against these determinants, and immunoradiometric assays have been developed to monitor antigen levels in the serum of cancer patients. This study was undertaken to determine whether concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen would provide a more precise correlation with tumor progression or regression than could be obtained with any single assay. Among 105 patients with surgically demonstrable epithelial ovarian carcinoma, serum CA 125 levels were elevated (greater than 35 U/ml) in 83%, CA 19-9, levels (greater than 37 U/ml) in 17%, and carcinoembryonic antigen levels (greater than or equal to 2.5 ng/ml) in 37%. Within individual samples, no correlation was found among values for the three markers, but patients with elevated CA 19-9 levels also had increased levels of CA 125. At least one of the three markers was elevated in 90% of the subjects. When 41 patients were monitored serially over 2 to 60 months, alterations in CA 125 levels correlated with disease progression or regression in 94% of instances, whereas alterations in CA 19-9 levels correlated in 33% and alterations in carcinoembryonic antigen levels in 25% of instances. Concomitant measurement of CA 125, CA 19-9, and carcinoembryonic antigen did not prove superior to measurement of CA 125 alone in the monitoring of patients with epithelial ovarian carcinoma.

Adenocarcinoma↗
PubMed1985

Predictive value of CA 125 antigen levels in second-look procedures for ovarian cancer.

Serum CA 125 levels were evaluated in 44 patients undergoing 56 second-look or subsequent laparoscopies (43) and laparotomies (13) for ovarian cancer. In each patient studied, a previous CA 125 level had been greater than or equal to 35 U/ml. Clinical or radiologic evidence of tumor was absent in all patients at the time of surgical evaluation. CA 125 levels were less than 35 U/ml in 36 cases (64%); 14 patients were free of tumor, while 22 were found to have tumor at surgery. CA 125 levels were greater than or equal to 35 U/ml in 20 cases; 18 had tumor at surgery, one has had recurrence of tumor, and the other remains clinically free of tumor at 3 months. A CA 125 level less than 35 U/ml was not predictive of the presence of intraperitoneal tumor; however, when tumor was present in this group of patients, the largest tumor mass did not exceed 1 cm. In contrast, a CA 125 level greater than or equal to 35 U/ml was a strong predictor of the presence of intraperitoneal tumor or future recurrence. These data suggest that second-look procedures may not be required in the select group of patients with CA 125 levels greater than or equal to 35 U/ml.

Adult↗
PubMed1986

The CA 125 assay as a predictor of clinical recurrence in epithelial ovarian cancer.

Serum CA 125 levels were obtained from 55 women with epithelial ovarian cancer before a second-look surgical procedure and serially thereafter. All patients were clinically and radiographically free of tumor at the time of the second-look operation and were followed to clinical recurrence. Median follow-up was 12 months. CA 125 levels obtained at the second-look operation had a sensitivity and specificity for predicting clinical recurrence of 94% and 88%, respectively. Patients with an elevated CA 125 level (greater than or equal to 35 U/ml) had a 60% chance of clinical recurrence within 4 months, while patients with levels less than 35 U/ml had a 5% chance of clinical recurrence over the same time period. Serial CA 125 levels obtained after second-look operations were strong predictors of clinical outcome, and distinctly different monitoring profiles were observed among those patients remaining clinically free of tumor and those suffering clinical recurrence. The CA 125 assay became elevated (greater than or equal to 35 U/ml) before clinical recurrence in 94% of 35 cases with a median lead time of 3 months. The CA 125 assay identifies patients destined to suffer a clinical recurrence and provides a warning measurable in months. This may have important implications for therapy.

Adult↗
PubMed1989

CA 125 levels in patients with ovarian carcinoma undergoing autologous bone marrow transplantation.

Levels of CA 125, determined in three patients with ovarian carcinoma undergoing autologous bone marrow transplantation, dropped significantly in the month after bone marrow transplantation. This decrease was linear by multiple regression analysis. The CA 125 decrease after bone marrow transplantation in patients with nonevaluable or stable disease may represent biologic response to high-dose therapy.

Adult↗
PubMed1989

Epidermal growth factor receptor expression in normal and malignant endometrium.

Epidermal growth factor receptor expression in fresh-frozen uterine tissues was studied with the use of monoclonal antibody 528, which recognizes an epitope on the external domain of the epidermal growth factor receptor. Immunohistochemically detectable epidermal growth factor receptor was seen in all uterine cell types in 19 of 20 normal uteri. Staining of endometrial glands and endometrial stromal cells was consistently greater than that of myometrium, and no variation in intensity or distribution of staining was seen during the menstrual cycle. Immunohistochemically detectable epidermal growth factor receptor was found less frequently in endometrial adenocarcinomas than in normal endometrium (p less than 0.01). Thirteen of 40 endometrial adenocarcinomas (32.5%) did not express detectable receptor. Epidermal growth factor receptor expression did not correlate with histologic grade, depth of myometrial invasion, estrogen-progesterone receptor status, the presence of extrauterine metastases, or the development of recurrent disease.

Adenocarcinoma↗
PubMed1989

Immunohistochemical expression of TAG-72 in normal and malignant endometrium: correlation of antigen expression with estrogen receptor and progesterone receptor levels.

TAG-72 is a tumor-associated antigen that is expressed by secretory endometrium and most endometrial adenocarcinomas. We used immunohistochemical techniques to quantitate expression of TAG-72, estrogen receptor, and progesterone receptor in 21 normal endometria and 44 endometrial adenocarcinomas. In normal cycling endometrial glands, TAG-72 expression was related inversely to expression of receptors for estrogen and progesterone. This suggests that TAG-72 expression in normal endometrium may be hormonally regulated. Ninety-one percent of endometrial adenocarcinomas expressed immunohistochemically detectable TAG-72. The magnitude of TAG-72 expression did not correlate with other known prognostic factors in endometrial cancer such as histologic grade, depth of myometrial invasion, surgical stage, or steroid receptor status. The production of TAG-72 by most endometrial adenocarcinomas may represent nonspecific expression by cells that have dedifferentiated.

Adult↗
PubMed1990

The prognostic significance of CA 125 half-life in patients with ovarian cancer who have received primary chemotherapy after surgical cytoreduction.

Fifty-four patients with advanced epithelial ovarian cancer were monitored with serial serum CA 125 levels after surgical cytoreduction and during multi-agent chemotherapy with cisplatin-containing regimens. CA 125 half-life of less than 20 days was associated with prolonged overall survival (p less than 0.015). In those patients who eventually were found to be disease-free at surgical surveillance procedures, normalization of serum CA 125 levels to less than 35 U/ml within 65 days of primary operation also suggested an improved survival (p less than 0.059).

Adenocarcinoma, Mucinous↗
PubMed1990

Preoperative evaluation of serum CA 125, TAG 72, and CA 15-3 in patients with endometrial carcinoma.

We evaluated 109 women with endometrial carcinoma to determine the accuracy of preoperative tumor-associated antigen levels (CA 125, CA 72, CA 15-3) for prediction of extrauterine disease and whether TAG 72, CA 15-3, or both would improve the predictive value of CA 125 alone. Eleven (12%) of 80 patients with disease confined to the uterus or positive cytologic findings had CA 125 values greater than 35 U/ml versus 12 (65%) of 20 patients with extrauterine metastasis. Therefore CA 125 values had sensitivity of 65% and specificity of 88%. The TAG 72 level was elevated (greater than 6 U/ml) in 4% of patients with localized disease and 30% with metastasis. CA 15-3 was elevated (greater than 30 U/ml) in 17% and 65% in these categories, respectively. TAG 72 or CA 15-3 levels did not improve the combination of sensitivity and specificity of CA 125 alone. In addition, only one of 10 patients with microscopic metastasis (three cases) or positive peritoneal cytology (seven) had elevation of any of these tumor-associated antigen levels. Failure to detect occult metastasis and a high false-positive rate limit the role of these tumor-associated antigen assays in the preoperative evaluation of patients with endometrial carcinoma.

Antigens, Neoplasm↗
PubMed1990

Heterogeneity of antigen expression in advanced epithelial ovarian cancer.

Immunohistochemical techniques were used to evaluate the expression of six antigens (CA 125, TAG 72, CA 19-9, OVTL3, DF3, and transferrin receptor) in frozen sections from the primary tumor and metastases of 20 patients with epithelial ovarian cancer. Heterogeneous expression of most antigens was observed within a given tumor nodule, but in each patient the proportion of cells expressing an antigen was similar in the primary tumor and metastases. To explore the stability of the antigenic phenotype of individual cells, we studied CA 125 expression in an ovarian cancer cell line. Cells were separated into CA 125-positive and -negative groups using fluorescence-activated cell sorting. After the two groups of cells were recultured separately, only 38% of cells originally sorted as CA 125 positive still expressed CA 125, whereas 27% of cells sorted as CA 125 negative expressed CA 125. That cells may gain or lose CA 125 expression in culture suggests that expression of CA 125 by ovarian cancer cells is not a stable trait.

Adenocarcinoma↗
PubMed1991

Increased serum levels of macrophage colony-stimulating factor in ovarian cancer.

Macrophage colony-stimulating factor is a cytokine that stimulates proliferation and differentiation of phagocytic cells. Macrophage colony-stimulating factor is produced by ovarian epithelial cancer cell lines and might provide a useful serum marker for the disease. Among sera from 69 patients with clinically apparent epithelial ovarian cancer, 47 (68%) had at least 2.5 ng/ml macrophage colony-stimulating factor, whereas only two of 80 apparently healthy donors (2.5%) had a comparable elevation of macrophage colony-stimulating factor. Circulating levels of macrophage colony-stimulating factor did not correlate with serum levels of CA 125. Moreover, 14 of 25 ovarian cancer patients (56%) with clinically evident disease and normal levels of CA 125 (less than 35 U/ml) had elevated levels of macrophage colony-stimulating factor. Among 29 patients with serum CA 125 levels less than 35 U/ml before positive surgical surveillance procedures, 9 (31%) had at least 2.5 ng/ml macrophage colony-stimulating factor. Elevated levels of macrophage colony-stimulating factor were also found in patients with carcinomas from other primary sites and in 31% of 134 patients with benign diseases. If intercurrent benign disease can be taken into account, macrophage colony-stimulating factor deserves further evaluation in combination with CA 125 in monitoring ovarian cancer.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. II. Relationship between receptor expression and response to epidermal growth factor.

Previously we have shown that epidermal growth factor acts as a mitogen for some, but not all, ovarian cancer cells in culture. In this study we examined the effect of epidermal growth factor on proliferation of normal human ovarian epithelial cells in monolayer culture. We found that epidermal growth factor stimulated twofold to fourfold increases in proliferation in epithelial cells from each of five normal ovaries (p less than 0.01). In addition, Scatchard analysis of binding of epidermal growth factor tagged with iodine 125 indicated the presence of high-affinity receptors in all of the ovarian epithelial cells and ovarian cancer cell lines. The number and affinity of receptors was similar in the normal epithelium and cancer cell lines, and there was no relationship between epidermal growth factor receptor number and responsiveness to epidermal growth factor. We conclude that human ovarian epithelial cells normally express epidermal growth factor receptors and that epidermal growth factor acts as a mitogen for these cells. Although the mitogenic response to epidermal growth factor often is attenuated in ovarian cancer cell lines, loss of responsiveness to epidermal growth factor does not appear to be due to decreased receptor expression.

Cells, Cultured↗
PubMed1991

Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease.

Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer.

Adenocarcinoma↗
PubMed1992

Stimulation of ovarian tumor cell proliferation with monocyte products including interleukin-1, interleukin-6, and tumor necrosis factor-alpha.

OBJECTIVE: We investigated whether monocyte-derived factors could stimulate the growth of ovarian cancer cells. STUDY DESIGN: Human peripheral blood monocytes or human monocyte-like cell lines THP-1 and U-937 were cultured with or without macrophage colony-stimulating factor, lipopolysaccharide, or phorbol myristate acetate. Culture supernatants or recombinant cytokines were assayed for growth stimulation of ovarian cancer cell lines by tritium-thymidine incorporation and direct cell counts followed by statistical analysis with Student t test. RESULTS: Conditioned medium from peripheral blood monocytes or from THP-1 or U-937 cells stimulated ovarian cancer cell growth. Interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6 also stimulated ovarian cancer cell growth, whereas macrophage, granulocyte, and granulocyte-macrophage colony-stimulating factor did not. Concentrations of tumor necrosis factor, interleukin-1, and interleukin-6 in conditioned medium could not account for all the growth stimulation, and activity remained after neutralization of tumor necrosis factor, interleukin-1, and interleukin-6 with antibodies. CONCLUSIONS: Interleukin-1, interleukin-6, tumor necrosis factor, and additional monocyte factor(s) could provide paracrine growth stimulation when monocytes are attracted to ovarian cancers that produce macrophage colony-stimulating factor.

Cell Division↗
PubMed1992

Regulation of growth of normal ovarian epithelial cells and ovarian cancer cell lines by transforming growth factor-beta.

OBJECTIVE: The purpose of this study was to study the role of transforming growth factor-beta in regulation of proliferation of normal and malignant ovarian epithelial cells. STUDY DESIGN: We examined production of and responsiveness to transforming growth factor-beta in primary monolayer cultures of epithelial cells from five normal human ovaries and in five ovarian cancer cell lines. RESULTS: In normal ovarian epithelial cells, proliferation always was inhibited by transforming growth factor-beta (greater than 40%) (p less than 0.01). Among the cancer cell lines, proliferation of one was markedly inhibited (greater than 95%) (p less than 0.01), two were only modestly inhibited (15% to 20%) (p less than 0.05), and two were unaffected. In addition, we found that all of the normal ovarian epithelial cells and four of five ovarian cancer cell lines produce transforming growth factor-beta ribonucleic acid and protein. CONCLUSIONS: These data suggest that transforming growth factor-beta may act as an autocrine growth inhibitory factor for normal ovarian epithelium in vivo. Because most of the ovarian cancer cell lines are relatively resistant to the growth inhibitory effect of transforming growth factor-beta and because one cell line does not produce transforming growth factor-beta, it is possible that loss of the transforming growth factor-beta pathway may play a role in the development of some ovarian cancers.

Cell Division↗
PubMed1992

The effect of interferon gamma on epidermal growth factor receptor expression in normal and malignant ovarian epithelial cells.

OBJECTIVE: We examined the effect of interferon gamma on proliferation and epidermal growth factor receptor expression in ovarian cancer cell lines and normal ovarian epithelial cells. STUDY DESIGN: The tritiated thymidine incorporation assay was used to assess the effect of interferon gamma on proliferation. Scatchard analysis of anti-epidermal growth factor receptor antibody binding, and Western blotting of immunoprecipitates was used to assess the effect of interferon gamma on epidermal growth factor receptor expression. RESULTS: Although interferon gamma elicited 30% to 40% decreases in proliferation, epidermal growth factor receptor expression was strikingly increased in all four ovarian cancer cell lines. Scatchard analysis indicated that this increase occurred primarily at the cell surface, but total cellular receptor levels also were increased. In contrast, interferon gamma treatment of normal ovarian epithelial cells affected neither proliferation nor epidermal growth factor receptor levels. CONCLUSION: Because the up-regulation of epidermal growth factor receptors by interferon gamma appears to be confined to malignant cells, interferon gamma may facilitate immunotherapy and imaging of ovarian cancers by means of immunoconjugates directed against the epidermal growth factor receptor.

Antibodies, Monoclonal↗
PubMed1993

Mutation of the p53 tumor-suppressor gene is not a feature of endometrial hyperplasias.

OBJECTIVE: Mutation and overexpression of the p53 gene occur in approximately 20% of endometrial carcinomas. To determine whether alteration of the p53 gene is an early event in endometrial carcinogenesis, we examined the p53 gene in endometrial hyperplasias. STUDY DESIGN: Genomic deoxyribonucleic acid was extracted from 117 endometrial hyperplasias (36 simple, 40 complex, 41 atypical) and 30 endometrial cancers. Exons 5 through 8 of the p53 gene were amplified by means of the polymerase chain reaction. Mutations in the p53 gene were sought with single-stranded conformation polymorphism analysis and confirmed by direct deoxyribonucleic acid sequencing. RESULTS: None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in three of 30 (10%) endometrial cancers (p < 0.02). The p53 mutations seen in three cancers were confirmed by direct sequencing (codons 157, 180, 272). CONCLUSION: Because it does not appear to be a feature of endometrial hyperplasias, mutation of the p53 gene may represent a relatively late event in endometrial carcinogenesis.

Base Sequence↗