Search PubMed⌕ Search

Biomedical subjects

R C Bast

Publications and source records attributed to R C Bast.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1991

Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer.

Previous studies in breast and bladder cancer have suggested that epidermal growth factor receptor is expressed by only a proportion of cancers and is associated with poor clinical outcome. We used a monoclonal antibody specifically reactive with the extracellular domain of the epidermal growth factor receptor to localize this receptor immunohistochemically in frozen sections of normal ovary and epithelial ovarian cancer. Normal ovarian epithelium was found to express epidermal growth factor receptor in all cases. Among 87 ovarian cancers, however, 23% did not express immunohistochemically detectable receptor. Epidermal growth factor receptor expression was not related to histologic grade or stage, but was associated with poor survival (p less than 0.05). The median length of survival of patients with tumors that did not express epidermal growth factor receptor was 40 months compared with 26 months in patients with tumors that did express epidermal growth factor receptor. As in breast and bladder cancer, expression of epidermal growth factor receptor in ovarian cancer appears to be a poor prognostic factor.

Antibodies, Monoclonal↗
PubMed1991

4-Hydroperoxycyclophosphamide purging of breast cancer from the mononuclear cell fraction of bone marrow in patients receiving high-dose chemotherapy and autologous marrow support: a phase I trial.

We designed an ex vivo bone marrow treatment for breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support (ABMS), using 4-hydroperoxycyclophosphamide (4-HC), an active derivative of cyclophosphamide with known activity against breast cancer. This phase I bone marrow purging trial used ficoll-separated mononuclear cells (MNC) (devoid of granulocytes and RBCs), as opposed to the buffy coat. Twenty-five patients with metastatic breast cancer were studied. Patients received three cycles of the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), fluorouracil, and methotrexate (Duke AFM) regimen, followed by marrow harvest. An MNC fraction of marrow was prepared and treated with 4-HC in concentrations of 20 micrograms/mL (four patients), 40 micrograms/mL (four patients), 60 micrograms/mL (nine patients), or 80 micrograms/mL (eight patients) and cryopreserved. Patients then received high-dose systemic cyclophosphamide, cisplatin, and carmustine, followed by infusion of the purged marrow. The study end point was marrow engraftment, defined as WBC count greater than 1,000 cells per microliter. At the first three dose levels (20, 40, and 60 micrograms/mL 4-HC), there was no significant delay in time to engraftment (19, 20, and 23 days, respectively) compared with the unpurged historical controls (17 days). At 80 micrograms/mL, engraftment was significantly delayed compared with the lower concentrations (P = .027), and further escalation of 4-HC was not attempted. A significant correlation was observed between the time of leukocyte engraftment and the 4-HC concentration (P = .017). With a methylcellulose-based tissue culture assay, we demonstrated a statistically significant correlation between the colony-forming unit-granulocyte-macrophage (CFU-GM) content in the purged marrow and the days to engraftment. Ninety-five percent of patients responded clinically to the entire program, 55% of them completely. Longer follow-up is required to assess the ultimate benefit of intensive therapy on long-term survival.

Adult↗
PubMed1991

The immunobiology and immunotherapy of ovarian cancer.

Small volume residual peritoneal disease in patients undergoing therapy for ovarian carcinoma remains an attractive, but elusive, target for immunobiological therapy. Hypothetical advantages and disadvantages of regional peritoneal therapy are being better defined through increased clinical experience and more sophisticated animal models. Developments in cytokine biology, adoptive cellular therapy, monoclonal antibody conjugation, and molecular biology continue to provide an exciting, and nearly overwhelming, array of reagents for clinical evaluation. Ongoing and anticipated investigational trials should provide intriguing data in years to follow.

Antibodies, Monoclonal↗
PubMed1991

Immunomagnetic purging of breast cancer from bone marrow for autologous transplantation.

Intensive chemotherapy with autologous bone marrow transplantation is a promising approach for the treatment of breast cancer, provided that clonogenic tumor cells do not contaminate the patient's bone marrow. We have previously demonstrated that a combination of 4-hydroperoxycyclophosphamide (4-HC) and immunomagnetic purging (IMP) with monoclonal antibodies and microspheres could remove 4-5 logs of clonogenic breast cancer cells from a 10-fold excess of human bone marrow cells. In the present report we have evaluated an apparatus for separating tumor cells from a large volume of human marrow. This apparatus will permit preparation of large volumes of purged marrow for use in studies of intensive therapy with autologous marrow support. Bone marrow progenitor cell (CFU-GM) recovery following this IMP technique was 85% of the unpurged control, and suggests that marrow recovery following high dose systemic chemotherapy will not be adversely affected. A phase I study to evaluate marrow reconstitution following IMP is underway. Preliminary data suggest that this IMP method will not delay engraftment in breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support, but further study is required.

Adenocarcinoma↗
PubMed1990

Reactivity of polyclonal and two monoclonal antibodies with cell subsets isolated from cystic fluids of ovarian serous neoplasms.

The distribution of antigenic determinants on a cellular level in serous ovarian neoplasms was evaluated using polyclonal and two monoclonal antibodies (OC 125 and 10B). The expression of antigens was estimated by an immunofluorescence test on each cell fraction isolated by density centrifugation from cystic fluids of individual malignant and benign ovarian tumors, taking into account the density and cytomorphologic features of cell subpopulations. It was found that the studied antibodies recognized different antigenic determinants. Significant immunologic heterogeneity of cells among and within individual tumors was shown. Our studies show the value of isolated cell subpopulations for comparing the reactivity of different antibodies and estimating their immunodiagnostic potency.

Antibodies, Monoclonal↗
PubMed1990

Gynecologic tumor markers.

The advent of monoclonal technology has increased the potential utility of antibody-dependent tumor marker assays in gynecologic oncology. The availability of unlimited quantities of several pure monoclonal antibodies directed against novel epitopes on tumor-associated antigens has permitted development of highly sensitive assays for serum markers. Traditional assays for human chorionic gonadotropin (hCG), NB/70K and TA-4 have been improved. CA 125 has provided a useful first-generation marker for monitoring ovarian cancer and triaging patients with pelvic masses, despite limitations in sensitivity and specificity. In the next decade, the challenge is to identify new markers that will complement CA 125 in monitoring ovarian cancer and facilitate screening for occult early-stage disease. Strategies involving multiple markers and modalities may be required. Some markers may emerge through a more fundamental knowledge of the biology of gynecologic neoplasms, including the expression of growth factors and their receptors. Finally, the application of monoclonal antibodies to immunohistochemistry and radionuclide imaging also may provide new areas of diagnostic application for monoclonal antibodies in gynecologic oncology.

Antibodies, Monoclonal↗
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↗
PubMed1990

Antigenic heterogeneity in human ovarian cancer.

Primary and metastatic tumor tissues from 21 patients with ovarian epithelial cancer were studied with a panel of 8 monoclonal antibodies. Primary tumors reacted with 1 to 7 antibodies (mean, 3.5). Heterogeneity was observed even within histologic subtypes. Comparison of metastases (including ascites) with their respective primaries revealed differences in antigen profile in each of 10 cases studied. In one patient variable antigen expression was observed in five ascites samples collected over a 12-month period. These observations of antigenic heterogeneity and modulation with respect to site and time suggest that single monoclonal antibody immunotherapy would not be appropriate for all patients or even for a single patient over time.

Adenocarcinoma↗
PubMed1990

Prospective evaluation of serum CA 125 levels in a normal population, phase I: the specificities of single and serial determinations in testing for ovarian cancer.

To determine the potential efficacy of the CA 125 assay as one component of a strategy for early detection of ovarian malignancy, serum CA 125 levels were determined in 1082 women 40 years of age or older in Stockholm. Initial serum CA 125 levels exceeded 35 U/ml in 36 women (3.3%) and 65 U/ml in 11 women (1.0%), placing the exact 95% upper confidence limits on false positive rates for a single screen at 4.3 and 1.7%, respectively. Follow-up CA 125 levels were obtained for those women with initially elevated levels and a group of age-matched controls. Mean CA 125 levels declined significantly for women with initially elevated levels (P = 0.0014). Interindividual variation and variation within individual subjects over the entire follow-up period were 52 and 35%, respectively. Of the 36 subjects with initially elevated serum CA 125 levels, only 2 showed a doubling of these levels; in only 1 of these 2 was this increase sustained. Intensive clinical follow-up with pelvic examination and ultrasonography, with investigators blinded to CA 125 results, led to the diagnosis of Stage III ovarian cancer in the latter individual. Diagnosis was made 21 months after the initially elevated serum CA 125 measurement and 15 months after the first measured doubling of that level. Because no other malignancies were identified at entry or during the follow-up period (median 560 days) in the women with elevated CA 125 levels, the specificity of the assay over that time period would have been 99.9% using the doubling of an initially elevated value as the criterion for determining positivity and 100% using as the criterion a sustained increase in level for those with initially elevated levels that doubled. These results support the continued investigation of longitudinally collected CA 125 levels to identify individuals at high risk for ovarian malignancy.

Adult↗
PubMed1990

CA 125 in peritoneal fluid and serum from patients with benign gynecologic conditions and ovarian cancer.

CA 125 was measured in peritoneal fluid from 200 patients with primary ovarian malignancies (35) and benign gynecologic conditions (165). In 86 patients CA 125 was measured both in peritoneal fluid and in serum. Patients with ovarian cancer had markedly greater serum CA 125 levels compared to patients with benign disease. CA 125 levels in peritoneal fluid were usually higher than serum levels. Twenty-six (93%) of 28 patients with ovarian cancer had peritoneal fluid levels which exceeded serum levels in paired samples. peritoneal fluid CA 125 values greater than 200 U/ml identified ovarian cancer patients with 96% sensitivity and 99% specificity. Serum CA 125 values greater than 35 U/ml identified ovarian cancer patients bearing ascites with a sensitivity of 99% and specificity of 94%. Only 2 of 165 patients with benign gynecological conditions had peritoneal fluid values above 200 U/ml. By contrast, only two values below 200 U/ml were found in ascitic fluids from 35 patients with ovarian cancer. CA 125 levels in peritoneal fluid deserve further evaluation for follow-up of patients with ovarian cancer.

Animals↗
PubMed1990

Detection of breast carcinoma cells in human bone marrow using fluorescence-activated cell sorting and conventional cytology.

Flow cytometry has been compared with conventional cytology as a method for detecting breast carcinoma cells in human bone marrow. Breast cancer cells from patient effusion fluids or from established cell lines were mixed with normal human bone marrow at dilutions ranging from 1:10 to 1:100,000. Cells were labeled with five directly fluoresceinated murine monoclonal antibodies reactive against epithelial cell surface determinants of 42, 55, 72, 200, and more than 200 kD. Fluorescence of tumor cells within the mixtures was then analyzed with the use of a fluorescence-activated cell sorter. In multiple experiments, one tumor cell in 10,000 nucleated marrow cells could be detected by flow cytometry. In addition, a linear correlation was observed over approximately 3 logs between the number of tumor cells added and the number of tumor cells detected. In a double-blind study comparing flow cytometry and cytology, flow cytometric analysis detected one tumor cell among 10,000 marrow precursors in 14 of 15 instances, whereas standard cytologic methods detected similar tumor contamination in 9 of 15 instances. Neither technique used individually could detect one tumor cell in 100,000 bone marrow cells. Used in combination, however, flow cytometry and cytology could detect one breast cancer cell among 100,000 normal marrow progenitors.

Antibodies, Monoclonal↗
PubMed1990

The role of tumor markers in gynecologic oncology.

Human chorionic gonadotropin is a highly sensitive and specific tumor marker for gestational trophoblastic neoplasia that accurately reflects tumor volume and the clinical course of disease. In women with endodermal sinus tumors and embryonal carcinomas, alpha-fetoprotein usually is a reliable marker, and it accurately predicts the presence of yolk sac elements in mixed germ cell tumors. CA 125 is the most widely utilized tumor marker presently available for use in patients with epithelial ovarian cancer. It has utility in monitoring therapy and differentiating benign from malignant pelvic masses. Measurement of serial CA 125 levels in postmenopausal women may facilitate screening for occult early stage disease. In the future, monoclonal antibodies that recognize tumor-associated antigens may prove useful for radionuclide imaging.

Antibodies, Monoclonal↗