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Biomedical subjects

R C Bast

Publications and source records attributed to R C Bast.

At least 217 records · Page 12Linked to original sources
PubMed1987

CA 125 for the monitoring of ovarian carcinoma during primary therapy.

Thirty-one patients with ovarian cancer were monitored with the CA 125 antigenic determinant in the interval between cytoreductive surgery and the completion of subsequent chemotherapy. Distinct CA 125 assay trends have emerged from prospective serial monitoring. Among patients who were clinically and surgically free of disease after the completion of cytoreductive chemotherapy, the CA 125 assay always fell to levels under 35 U/mL within the first three months of cytoreductive chemotherapy, and stayed at low levels. Patients with partial cytoreduction operations had decreases in serum CA 125 levels only if there was a response to further therapy. The rate of fall of the CA 125 levels correlated with clinical outcome. All 13 patients with serum CA 125 above 35 U/mL after three months of treatment invariably had persistent tumors after subsequent chemotherapy, whereas in patients showing reduction of the CA 125 to levels below 35 U/mL, there were no surgically detectable tumors. Measurement of CA 125 during treatment might permit an early change to alternative and optimal forms of therapeutic management. The CA 125 level three months after treatment appears to be a critical predictor of response to therapy.

Antigens, Neoplasm↗
PubMed1987

Serum CA 125 levels in a group of nonhospitalized women: relevance for the early detection of ovarian cancer.

Serum samples were collected from 915 nonhospitalized Roman Catholic nuns with a median age of 55 years (range 19-94 years). Using an immunoradiometric assay, serum CA 125 levels ranged from 0-574 U/mL with a median of 10.5 and mean of 14.3 U/mL. Thirty-six women (3.9%) had serum levels greater than 35 U/mL, and only seven (0.76%) had serum CA 125 levels above 65 U/mL. In only 14 (2.4%) of 586 women aged 50 or older were CA 125 levels above 35 U/mL, and in only three (0.51%) of this group did levels exceed 65 U/mL. Among the seven women with levels above 65 U/ML, five were found to have benign or malignant neoplasms or other masses at the time of entry into the study or during the follow-up interval (mean 311 +/- 103 days). Moreover, in six of seven members of this "false positive" group, some disorder was diagnosed during the study period that might have elevated the CA 125 level. No correlation was found between serum CA 125 levels and a variety of nonmalignant disorders or a variety of concurrent medications. The apparent specificity of the CA 125 assay in this study population suggests that, if used in conjunction with other tests to discriminate ovarian carcinoma from disorders that could elevate serum CA 125 levels, this assay might be a potential component of a strategy aimed at the early detection of ovarian cancer.

Adult↗
PubMed1986

Treatment of murine peritoneal macrophages with bacterial lipopolysaccharide alters expression of c-fos and c-myc oncogenes.

Expression of the c-fos, c-myc, and c-fms proto-oncogenes has been studied in thioglycollate-elicited murine peritoneal macrophages after exposure to lipopolysaccharide (LPS). After incubation with LPS (20 ng/ml), a transient and rapid induction of the expression of c-fos and c-myc oncogenes could be observed, whereas the RNA levels for c-fms were not affected. Treatment with lipid A, the active moiety of the LPS molecule, increased the c-fos and c-myc expression to a comparable degree. Similar induction of c-fos and c-myc was observed after treatment with phorbol myristate acetate, suggesting that this effect of LPS on murine macrophages might be mediated through stimulation of protein kinase C. Under similar experimental conditions, LPS treatment of macrophages did not trigger DNA synthesis. Treatment with LPS blocked DNA synthesis in macrophages treated with L cell-conditioned medium containing colony-stimulating factor. Thus changes in c-fos and c-myc expression may be elements in the complex series of biochemical events that contribute to macrophage activation and are not necessarily related to induction or priming for cellular proliferation.

Animals↗
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↗
PubMed1986

Antigenic heterogeneity among Burkitt's lymphoma cells surviving treatment with monoclonal antibody and complement.

Selective removal of malignant cells from human bone marrow is one requirement for autologous bone marrow transplantation. In earlier studies treatment with multiple monoclonal antibodies and C' was more effective than treatment with individual reagents in eliminating clonogenic Burkitt's lymphoma cells from a twenty-fold excess of human bone marrow. To explore possible mechanisms underlying the additive or synergistic effects observed with multiple reagents, clones of malignant cells that have survived treatment with antibody and C' have now been isolated at limiting dilution. Marked heterogeneity has been observed in binding of different monoclonal antibodies and in resistance to C'-dependent lysis among these different clones. Phenotypic traits were stable for at least two weeks in culture. Clones that survived treatment with the J5 anti-CALLA antibody and C' exhibited a relative decrease in CALLA expression but did not exhibit an increased susceptibility to lysis by anti-CALLA and C'. No selective decrease in gp-26 or B1 was observed in clones treated with J2 or anti-B1. A correlation between CALLA and gp-26 expression was observed in clones treated with J2 and anti-B1, but no clear correlation was observed between antigen expression and susceptibility to C'-dependent lysis. In this model system, escape from C' dependent cytotoxicity does not appear related to the existence of phenotypically stable C' resistant variants within the tumor cell population.

Animals↗
PubMed1986

Elevated serum concentrations of CA-125 in patients with advanced endometriosis.

CA-125 is a high-molecular-weight glycoprotein that is expressed on the cell surface of some derivatives of embryonic coelomic epithelium. Based on results of an immunoradiometric assay developed to detect CA-125 in peripheral blood, 82% of patients with ovarian cancer and less than 1% of apparently healthy controls have elevated peripheral blood levels of CA-125. Because endometriotic lesions are likely to be derivatives of embryonic coelomic epithelium, the authors investigated serum CA-125 levels in patients with endometriosis. Preoperative serum CA-125 concentrations were measured in 147 patients undergoing diagnostic laparoscopy or laparotomy. Serum CA-125 concentrations were elevated in patients with stage III or IV endometriosis, compared with controls with negative diagnostic laparoscopies (66.5 +/- 14.5 versus 8.20 +/- 0.59 U/ml, mean +/- standard error of the mean; P less than 0.001). Fifty-four percent of patients with stage III or IV endometriosis and 0% of the controls had CA-125 levels greater than 35 U/ml. Occasional patients with stage II endometriosis (13%), leiomyomata uteri (14%), and chronic pelvic inflammatory disease (5%) also had serum CA-125 concentrations greater than 35 U/ml. Immunocytochemical techniques demonstrated the presence of CA-125 on the cell surface of endometriotic lesions.

Adolescent↗
PubMed1986

CA 125 serum levels correlated with second-look operations among ovarian cancer patients.

CA 125, which is an antigenic determinant expressed by many epithelial ovarian cancers, is measured in serum using a solid phase immunoradiometric assay. Sera from 55 patients who were in clinical remission and underwent a second-look operation to assess disease status after chemotherapy were studied prospectively. All patients had the CA 125 assay performed within one week before their second-look operation. Twenty-four patients (44%) had no histologic or cytologic evidence of disease, seven patients (13%) had microscopic disease, 13 patients (24%) had disease measuring 1 mm to 1.5 cm, and ten patients (18%) had disease greater than or equal to 1.5 cm in maximum tumor dimension. None of the 24 patients with a negative second-look operation had a positive CA 125 antigen level (greater than or equal to 35 U/mL), compared with six of 20 patients (30%) with less than 1.5 cm disease, and six of ten (60%) with greater than or equal to 1.5 cm disease (P less than .0001). All 12 patients with an elevated CA 125 antigen level (greater than or equal to 35 U/mL) had disease discovered at their second-look operation. Thus, in this setting the predictive value of a positive CA 125 titer (greater than or equal to 35 U/mL) was 100%. The predictive value of a negative CA 125 antigen level (less than 35 U/mL) was 56%, ie, the test did not exclude the presence of disease in 44% of patients with a positive second look. The maximum tumor size associated with at least one prior negative antigen level was 1.9 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1986

Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer.

Serum CA 125 levels were measured preoperatively in 100 women undergoing diagnostic laparotomy for palpable adnexal masses. All 11 patients with frankly malignant nonmucinous ovarian carcinoma had serum CA 125 levels greater than 35 U/mL and nine of the 11 had serum CA 125 levels greater than 65 U/mL. If patients with mucinous and borderline lesions were included, serum CA 125 was greater than 35 U/mL in 11 of 18 and greater than 65 U/mL in nine of 18 patients. Among 14 individuals with pelvic masses and CA 125 greater than 65 U/mL, 13 had some form of gynecologic malignancy. These results suggest that CA 125 assay can be used as a diagnostic adjunct for discriminating benign from malignant pelvic masses.

Adenocarcinoma, Mucinous↗
PubMed1986

Characterization of the CA 125 antigen associated with human epithelial ovarian carcinomas.

The murine monoclonal antibody OC125 reacts with an antigenic determinant (CA 125) found on a high-molecular-weight glycoprotein complex present in the serum of greater than 80% of women with epithelial ovarian cancer. The antigen expressing CA 125 (CA 125 antigen) isolated from the sera of ovarian carcinoma patients was shown by gel electrophoresis, molecular size exclusion chromatography, and buoyant density ultracentrifugation to have similar immunological and physical characteristics to antigen isolated from an ovarian cancer cell line (OVCA 433) and human milk. A composite sodium dodecyl sulfate: polyacrylamide:1.0% agarose gel resolved the CA 125 activity from the three sources of antigen into disperse bands of similar electrophoretic mobilities with apparent masses of 200,000 to 1 million daltons. The buoyant densities of the CA 125 antigen complexes from human serum, OVCA 433 cells, and human milk were in the range of 1.36 to 1.46 g/ml. Isolation of CA 125 antigen of higher purity from OVCA 433 supernatant was achieved by a series of steps including OC125 immunoaffinity chromatography. Subsequent resolution of this purified CA 125 antigen complex by sodium dodecyl sulfate:polyacrylamide gel electrophoresis gave rise to a band at approximately 200,000 daltons. Treatment of the CA 125 antigen from OVCA 433 cells with 10 mM periodic acid resulted in no loss of activity. Reduction and alkylation in 6 M guanidine-HCl or treatment at 100 degrees C for 20 min resulted in complete loss of activity. Exoglycosidase treatments did not result in loss of activity, whereas protease digestion eradicated all activity. These data strongly suggest that the CA 125 antigenic determinant is composed of, at least in part, conformationally dependent peptide.

Antigens, Neoplasm↗
PubMed1986

Elimination of clonogenic tumor cells from human bone marrow using a combination of monoclonal antibody:ricin A chain conjugates.

Effective autologous bone marrow transplantation for leukemia and lymphoma is likely to depend upon the selective removal in vitro of malignant cells from normal human bone marrow precursors. Highly specific cytotoxic conjugates formed by coupling ricin A chain to monoclonal antibodies might prove useful for the selective elimination of malignant cells. Consequently, ricin A chain conjugates have been prepared with several different murine monoclonal antibodies and tested for their ability to eliminate clonogenic Burkitt's lymphoma cells from an excess of human bone marrow. The most active reagents included an antibody:A chain conjugate which bound to the nonpolymorphic chain of the la molecule and another which reacted with the mu heavy chain of cell surface immunoglobulin. Conjugates formed with anti-common acute lymphoblastic leukemia antigen, anti-Mr 26,000 glycoprotein, and anti-B1 were much less active on these Burkitt's cells, contrasting with results of complement-dependent tumor cell lysis. Tumor cell kill was partially inhibited by the addition of greater than 2 X 10(6) human bone marrow cells/ml but could be potentiated by increasing the concentration of conjugate or by the addition of 10 mM ammonium chloride. In the presence of ammonium chloride, at least 4 logs of clonogenic tumor cells could be eliminated within 24 h from a 20-fold excess of bone marrow using 10(-7) M ricin A chain linked to one or two different antibodies. Similar treatment of normal human bone marrow temporarily inhibited granulocyte-macrophage colony-forming units (cell) formation but did not compromise establishment of continuous bone marrow cultures. The degree of selective elimination of tumor cells with A chain antibody conjugates was comparable to that achieved with 4-hydroperoxycyclophosphamide or with multiple monoclonal antibodies and complement.

Ammonium Chloride↗
PubMed1986

Prediction of the optimal timing of bone marrow reinfusion after high dose chemotherapy.

Autologous bone marrow transplantation allows the use of high dose chemotherapy by obviating dose limiting myelosuppression. The pharmacology of high dose chemotherapy has been inadequately explored, yet this information is critical to determine the timing of marrow infusion and assure that engraftment is not compromised. We have used the Salmonella mutagenesis test (SMT) and colony forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte assay to evaluate the optimal time for marrow infusion after therapy with high dose combinations of alkylating agents (Solid Tumor Autologous Marrow Support Program) in seven patients. The SMT is sensitive, rapidly performed, and has been used to detect mutagenic activity in urine following administration of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea. In parallel, determination of colony forming ability of the patients own bone marrow (colony forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte assay), when cocultured with autologous serum obtained before and after treatment, provided an assay for circulating marrow toxic drugs or metabolites. The onset of mutagenic activity in the SMT and the in vitro appearance of myelotoxicity by autologous serum in the colony forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte assay were concurrent, and these activities returned to base line at the time of marrow infusion (72 h posttreatment). One patient of the seven was excreting mutagens (TA100 strain only) at the time of marrow reinfusion; he developed hepatic venoocclusive disease, and delayed engraftment. These observations suggest that as high dose regimens evolve the SMT may serve as a rapid, sensitive indicator of the circulation and excretion of toxic compounds, and thereby assist in predicting the optimum time of bone marrow reinfusion.

Alkylating Agents↗
PubMed1985

A study of the NB/7OK and CA 125 monoclonal antibody radioimmunoassays for measuring serum antigen levels in ovarian cancer patients.

Serum levels of tumor antigens NB/7OK and CA 125 were determined in 101 samples by radioimmunoassays with the use of murine monoclonal antibodies. Among serum samples from ovarian cancer patients, elevated NB/7OK levels were found in 87% of samples that contained elevated CA 125 levels. With either assay, only 2% of patients with nonmalignant diseases had elevated antigen levels. No quantitative correlation was found, however, between levels of NB/7OK and CA 125. When antigen present in serum was purified by gel filtration on Sephacryl S-200, CA 125 eluted with an apparent molecular weight in excess of 100 kilodaltons whereas NB/7OK eluted with an apparent molecular weight of 70 kilodaltons. Thus the NB/7OK and CA 125 radioimmunoassays appear to measure two different populations of antigenic material.

Antibodies, Monoclonal↗
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↗
PubMed1985

Elevation of serum CA 125 prior to diagnosis of an epithelial ovarian carcinoma.

In a single fortuitous case it has been possible to measure serum levels of CA 125 during 3 years preceding the diagnosis of an epithelial ovarian carcinoma. CA 125 levels were elevated 10-12 months prior to clinical detection of the malignancy. CA 125 deserves further evaluation as a marker for early detection of ovarian cancer.

Agammaglobulinemia↗
PubMed1985

Carcinoma of the pancreas. Therapeutic efficacy as defined by a serodiagnostic test utilizing a monoclonal antibody.

DU-PAN-2 is a high molecular weight glycoprotein defined by a murine monoclonal antibody elicited to a pancreatic ductal adenocarcinoma cell line. This monoclonal antibody recognizes an oncofetal antigen present on the surface of pancreatic tumor cells. The antigen has also been detected in the sera of patients with adenocarcinoma of the pancreas by a competition radioimmunoassay (RIA). Ninety-four per cent (31/33) of patients with pancreatic adenocarcinoma in this study had DU-PAN-2 serum antigen levels greater than 300 units/ml by RIA, whereas sera from normal adults had serum levels less than 300 units/ml. Serial studies of DU-PAN-2 serum antigen in pancreatic cancer patients with elevated DU-PAN-2 serum levels (mean: 2873 units/ml) and surgically resectable neoplasms demonstrated a return to the normal range within 1 to 3 weeks after surgery in five of six patients. Five patients in clinical remission had normal DU-PAN-2 serum levels (mean: 110 units/ml). With tumor progression, however, the DU-PAN-2 level increased in all patients (mean: 2835 units/ml) an average of 2 months before evidence of progressive disease by clinical parameters. Serial DU-PAN-2 determinations are sensitive monitors of the progression of pancreatic cancer and may be useful as early indicators of response to therapy.

Adenocarcinoma↗