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Biomedical subjects

R C Bast

Publications and source records attributed to R C Bast.

At least 235 records · Page 13Linked to original sources
PubMed1985

Circulating DF3 and CA125 antigen levels in serum from patients with epithelial ovarian carcinoma.

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300-kilodalton (kd) mammary epithelial antigen. A sequential double-determinant enzyme-linked immunoassay (EIA) has been developed to monitor circulating DF3 antigen. Previous studies have demonstrated that the use of the DF3 EIA provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer. In the present study, we have monitored circulating DF3 antigen in the serum of patients with epithelial ovarian carcinomas and non-ovarian gynecologic malignancies. Twenty-one of 45 patients (47%) with ovarian carcinoma had elevated DF3 antigen levels (greater than or equal to 30 U/mL). In contrast, three of 20 patients (15%) with non-ovarian gynecologic malignancies, and only four of 59 control women (7%) had elevation of circulating DF3 antigen. The difference between DF3 antigen values from patients with ovarian cancer and from controls was significant (P less than .001). The elevation of circulating DF3 antigen in ovarian cancer patients has also been confirmed by transblot assays. MAb DF3 reactivity occurred predominately with circulating antigens of molecular weights (mol wt) ranging from 300 to 450 kd. Furthermore, DF3 antigen levels have been shown to correlate with progression of disease in six patients with ovarian cancer and after resection of disease in two others. The half-life of circulating DF3 antigen was approximately 45 to 60 days. The results also demonstrate that DF3 antigen is distinct from CA125, a glycoprotein associated with coelomic epithelium and developmental amnion. The use of both the DF3 EIA and the immunoradiometric assay previously described to detect circulating CA125 suggests that determining levels of both markers may enhance the sensitivity of monitoring the course of ovarian cancer. Furthermore, the use of both assays may be useful in distinguishing ovarian cancer from other malignancies.

Adult↗
PubMed1985

Elimination of malignant clonogenic cells from human bone marrow using multiple monoclonal antibodies and complement.

A clonogenic assay has been developed that utilizes Burkitt's lymphoma tumor cell lines to detect elimination of up to 5 logs of tumor cell contamination within human bone marrow. Different Burkitt's lymphoma lines bear one or more of a group of markers, including common acute lymphoblastic leukemia antigen gp26 (glycoprotein with a molecular weight of 26,000), B1, surface membrane immunoglobulin, HLA, beta 2-microglobulin, and Ia. Burkitt's tumor cells of the Namalwa line have been mixed with a 20-fold excess of irradiated human bone marrow cells. After treatment with one or more monoclonal antibodies and rabbit complement (RC), mixtures have been grown on a monolayer of irradiated human bone marrow cells and tumor cells enumerated by limiting dilution. Multiple treatments with antibody and RC were more effective than a single treatment in destroying clonogenic tumor cells which bore relevant determinants. Human serum components inhibited the lytic activity of RC in the presence of murine monoclonal antibodies. The total concentration of bone marrow cells proved critical in determining the complete elimination of tumor. Incubation of the Namalwa tumor cell line with RC and the J2 anti-gp26 eliminated more than 3 logs of malignant cells from a 20-fold excess of human bone marrow. Combinations of two monoclonal antibodies were more effective than any single antibody in eliminating Namalwa cells. A combination of three monoclonal reagents was no more effective than a combination of J2 and B1 or J2 and J5 in eliminating Namalwa cells. Treatment of human bone marrow with three antibodies and RC did not, however, produce a selective loss of nonmalignant GM-CFU-C, CFU-E, or BFU-E.

Antibodies, Monoclonal↗
PubMed1985

Elimination of clonogenic Burkitt's lymphoma cells from human bone marrow using 4-hydroperoxycyclophosphamide in combination with monoclonal antibodies and complement.

One requirement for autologous bone marrow transplantation is the selective removal of malignant cells from normal marrow precursors. Development of a clonogenic assay that detects elimination of up to 5 logs of Burkitt's lymphoma cells in the presence of a 20-fold excess of human bone marrow has permitted the evaluation of two different methods for the selective removal of malignant cells. Treatment with 4-hydroperoxycyclophosphamide (4-HC) (60 to 100 micrograms/mL) eliminated 2.0 to 3.5 logs of clonogenic cells. Antitumor activity depended upon the concentration of 4-HC and the length of incubation, but not upon the concentration of normal bone marrow cells. Comparable removal of clonogenic Burkitt's cells was achieved by treatment with rabbit complement (C') and a combination of J5 anti-common acute lymphoblastic leukemia antigen (J5 anti-CALLA), J2 anti-gp 26, and the B1 anti-B1 murine monoclonal antibodies. A combination of 4-HC and monoclonal antibodies proved slightly but significantly more effective than either single agent in eliminating clonogenic tumor cells. Although treatment with 4-HC markedly reduced granulocyte-macrophage colony-forming units-C (GM-CFU-C) content of human bone marrow, neither treatment with 4-HC nor treatment with monoclonal antibodies and C' eliminated precursor cells that could generate new GM-CFU-C after growth in continuous bone marrow cultures. Our data suggest that treatment with 4-HC in combination with multiple monoclonal antibody reagents could be a safe and effective method of eliminating clonogenic tumor cells from human bone marrow.

Antibodies, Monoclonal↗
PubMed1984

Anti-B1 monoclonal antibody and complement treatment in autologous bone-marrow transplantation for relapsed B-cell non-Hodgkin's lymphoma.

Eight patients with relapsed B-cell non-Hodgkin's lymphoma were treated with intensive chemoradiotherapy and reconstituted with autologous bone marrow rendered free of tumour cells by the B-cell-specific monoclonal antibody anti-B1 and complement. Before the autologous marrow transplantation patients were induced with chemotherapy, radiotherapy, or both, into a minimum disease state with less than 5% bone-marrow involvement with tumour. All patients treated achieved a complete clinical response and had stable haematological engraftment by 8 weeks. No significant acute or chronic toxic effects have occurred. B cells could be detected by 2 months after transplantation and normal immunoglobulin levels were achieved by 6 months. Six of eight patients are disease free in unmaintained remission more than 20, 19, 10, 8, 5, and 3 months after transplantation.

Adult↗
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↗
PubMed1984

Elevation of serum CA125 in carcinomas of the fallopian tube, endometrium, and endocervix.

An immunoradiometric assay with the use of a monoclonal antibody can detect an antigenic determinant (CA125) in peripheral blood from more than 80% of patients with epithelial ovarian cancer. In this report elevated levels of CA125 were detected in serum from patients with adenocarcinomas of the fallopian tube, endometrium, and endocervix. Among patients with endometrial cancer, CA125 levels were elevated in recurrent or disseminated disease but not with tumors confined to the uterus.

Adenocarcinoma↗
PubMed1984

Somatic activation of rasK gene in a human ovarian carcinoma.

A tumor isolate from a patient with serous cystadenocarcinoma of the ovary contained an activated rasK gene detected hy transfection of NIH/3T3 cells. In contrast, DNA from normal cells of the same patient lacked transforming activity, indicating that activation of this transforming gene was the consequence of somatic mutation in the neoplastic cells. The transforming gene product displayed an electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels that differed from the mobilities of rasK transforming proteins in other tumors, indicating that a previously undescribed mutation was responsible for activation of rasK in this ovarian carcinoma.

Animals↗
PubMed1984

Monoclonal antibody immunoradiometric assay for an antigenic determinant (CA 125) associated with human epithelial ovarian carcinomas.

CA 125 is an antigenic determinant expressed by greater than 80% of nonmucinous epithelial ovarian carcinomas. An immunoradiometric assay has been developed using a murine monoclonal antibody (OC125) to quantitate CA 125 in human serum. This immunoradiometric assay was optimized for specificity, sensitivity, and performance characteristics. Using a simultaneous immunoradiometric assay, the mean CA 125 concentration in 56 sera from healthy individuals was 11.2 +/- 5.4 (S.D.) units/ml, with 9.7 +/- 3.2 units/ml for 30 males and 13.1 +/- 6.8 units/ml for 26 females. A reference value of 35 units/ml included all 56 normals and excluded 86 of 105 (82%) ovarian carcinoma patients. This reference value also excluded 9 of 142 patients (6%) with benign diseases, but if the upper limit of normal was set at 65 units/ml, only 3 of 142 (2%) patients with benign diseases had elevated serum CA 125 levels, whereas 77 of 105 (73%) ovarian carcinoma patient sera remained positive. The ability of researchers, with this assay, to discriminate between CA 125 values in sera of patients with ovarian carcinoma and those of healthy individuals and patients with benign disease suggests that the assay deserves continued evaluation for monitoring and early diagnosis of ovarian cancer.

Age Factors↗
PubMed1984

Interaction of monoclonal antibodies with cell surface antigens of human ovarian carcinomas.

Two monoclonal antibodies, OC 125 and OC 133, bind to distinct determinants on the surface of human epithelial ovarian carcinoma cell lines. OC 125 and OC 133 recognize determinants on molecules with molecular weights greater than 200,000 and 80,000, respectively. When binding to four different cell lines was compared, apparent affinity constants for OC 125 ranged from 3.1 X 10(9) to 6.0 X 10(7) M-1, whereas those for OC 133 ranged from 1.6 X 10(9) to 8.5 X 10(8) M-1. An estimate of the number of antigenic determinants per cell ranged from 1.0 X 10(7) to 2.8 X 10(5) for OC 125 and from 4.0 X 10(5) to 3.4 X 10(4) for OC 133. Antigenic determinants recognized by OC 125 and OC 133 could be detected in spent culture medium. When radiolabeled OC 125 was incubated with each of four ovarian tumor cell lines, approximately 90% of the antibody remained bound to the tumor cell surfaces for more than 20 hr. Similar binding of OC 133 was observed with three of the four ovarian tumor cell lines. By contrast, greater than 70% of OC 133 antibody was either shed or endocytosed after binding to OVCA 433 cells over the same period. Antigenic modulation was not induced by either antibody interacting with any of the four cell lines. These data suggest that antigen may be lost from the surface of human ovarian carcinoma cells by several different mechanisms and that antigen release is not inconsistent with binding of radiolabeled antibody to the tumor cell surface for prolonged periods.

Antibodies, Monoclonal↗
PubMed1984

CA125 antigen levels in obstetric and gynecologic patients.

An immunoradiometric assay using a monoclonal antibody detects an antigenic determinant (CA125) that is present in more than 80% of epithelial ovarian cancers. CA125 levels are elevated in the sera of 16% of women in the first trimester of pregnancy and is found in very high concentration in amniotic fluid. In 988 nonpregnant patients with benign gynecologic disorders, CA125 was greater than 65 U/mL in 1% on a single determination and in 0.5% with two determinations. Given the low rate of positivity in benign gynecologic disease, the CA125 assay may deserve further evaluation for the early detection of ovarian carcinoma.

Adult↗
PubMed1984

Lymphocyte cytotoxicity in the peritoneal cavity and blood of patients with ovarian cancer.

After an intensive course of combination chemotherapy, 16 patients with minimal residual ovarian cancer that was documented at second-look laparotomy, had an indwelling Tenckhoff catheter placed and underwent multiple peritoneal saline lavages. Lymphocyte-enriched populations from the peritoneal cavity and peripheral blood were obtained by density gradient centrifugation and examined for cell-surface phenotype and a variety of immune functions, including natural killer cytotoxicity and antibody-dependent cell-mediated cytotoxicity. Phenotypic characterization revealed that peritoneal lymphocytes consisted primarily of T cells and cells bearing receptors for the crystallizable fragment of immunoglobulin G (IgG) (crystallizable fragment-receptor), and contained a very low number of B cells. Peritoneal natural killer lymphocyte cytotoxicity and antibody-dependent cell-mediated cytotoxicity were very low in all but two patients. Incubation of peritoneal lymphocytes with Corynebacterium parvum and interferon in vitro did not result in augmented cytotoxicity against susceptible targets. Supernatants from cultured peritoneal cells of all patients markedly inhibited natural cytotoxic activity of normal donor blood lymphocytes. These results suggest that lymphocytes collected from the peritoneal cavity of patients with minimal residual ovarian cancer are deficient in natural and antibody-dependent cytotoxic effector function. This deficiency may influence the host's ability to control the spread and proliferation of tumor cells in the peritoneal cavity.

Adenocarcinoma↗
PubMed1983

Expression of major histocompatibility antigens and nature of inflammatory cellular infiltrate in ovarian neoplasms.

Expression of histocompatibility antigens and the intensity of inflammatory cellular infiltrate were evaluated in frozen tissue sections from 70 human ovarian tumors and six normal ovaries using monoclonal antibodies and an avidin-biotin immunoperoxidase technique. In the normal human ovary, surface epithelial cells, mature granulosa cells and lutein cells reacted with anti-HLA-A,B,C (HLA) and beta2-microglobulin antibodies but not with anti-Ia (Ia-like, HLA-DR). Stromal cells and granulosa cells of the primordial follicles did not react with any of the antibodies. Among the neoplasms examined, all benign epithelial tumors, 86% of borderline an 81% of malignant epithelial tumors reacted with anti-HLA and/or beta2-microglobulin antibodies. HLA-negative epithelial tumors were of serous or endometrioid types. Although Ia was not found in normal ovarian surface epithelium, the antigen could be detected in 44% of benign, and 43% of borderline and malignant epithelial ovarian tumors. Mononuclear cellular infiltrate was generally scarce in ovarian tumors and consisted mainly of T cells. Malignant epithelial tumors contained significantly more T cells than did benign tumors. More T cells were observed in HLA-positive ovarian tumors than in HLA-negative neoplasms, but the difference did not achieve statistical significance. No correlation could be found between Ia expression and the intensity of T-cell infiltrate. Significantly more T8 and Leu-3a-positive cells were found in the tumor stroma than amongst neoplastic cells. HNK-I-positive natural killer cells, OK-MI-positive macrophages and BI-positive B lymphocytes were rarely encountered either in the tumor stroma or between adjacent tumor cells.

Antibodies, Monoclonal↗
PubMed1983

A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer.

The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas. An assay has been developed to detect CA 125 in serum. By this assay, only 1 per cent of 888 apparently healthy persons and 6 per cent of 143 patients with nonmalignant disease had serum CA 125 levels above 35 U per milliliter. In contrast, 83 of 101 patients (82 per cent) with surgically demonstrated ovarian carcinoma had elevated levels of antigen. In 38 patients with epithelial ovarian carcinoma monitored on 2 to 18 occasions during 2 to 60 months, antigen levels ranged from less than 1 to more than 8000 U per milliliter. Rising or falling levels of CA 125 correlated with progression or regression of disease in 42 of 45 instances (93 per cent). Determination of CA 125 levels may aid in monitoring the response to treatment in patients with epithelial ovarian cancer.

Adenocarcinoma↗
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↗
PubMed1983

Contrasting effects of cyclophosphamide and prednisolone on the phenotype of human peripheral blood leukocytes.

The cell surface phenotype of human peripheral blood mononuclear cells has been characterized before and after intravenous injection of cyclophosphamide or prednisolone. Low doses of cyclophosphamide (100-600 mg/m2) temporarily decrease levels of circulating B lymphocytes. Slightly higher doses of cyclophosphamide (200-600 mg/m2) produce transient depression of T8-, M1-, and Ia-positive cells. After doses of 200-400 mg cyclophosphamide/m2, T4-positive cells are spared, resulting in a transient elevation of the T4/T8 ratio. With higher doses of cyclophosphamide (greater than or equal to 600 mg/m2), all T cells are affected and the T4/T8 ratio declines to pretreatment levels. By contrast, intravenous injection of prednisolone at 40 mg/m2 reduces the T4/T8 ratio. Levels of both T4 and T8 cells decline, but T4 cells are affected more markedly than T8 cells.

Adult↗