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At least 361 records · Page 20Linked to original sources
PubMed1988

An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma.

Preoperative serum CA 125 levels were determined for 36 patients with Stage I and II ovarian carcinoma. Levels ranged from 9 to 1962 U/ml with a mean of 216 U/ml. In Stage I patients, CA 125 levels averaged 133 U/ml and in Stage II patients 382 U/ml. Nine of 24 Stage I (38%) and 9 of 12 Stage II patients (75%) had CA 125 levels in excess of 65 U/ml in a population somewhat overrepresented in mucinous tumors. Patients with non-mucinous neoplasms had CA 125 elevations more often--in 75% of the cases--than those with mucinous tumors. A larger study will be required to more precisely estimate the fraction of early stage patients with elevated preoperative serum CA 125 levels; however, this investigation demonstrates an assay sensitivity minimally adequate to initiate a pilot evaluation of serum CA 125 levels in a population at risk for ovarian carcinoma.

Antigens, Neoplasm↗
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↗
PubMed1992

Ploidy analysis of epithelial ovarian cancers using image cytometry.

We used a computerized image analysis system to determine the DNA content of 103 epithelial ovarian cancers using touch imprints of frozen tumor samples. Similar to prior studies of ploidy using flow cytometry, we found that most ovarian cancers (78%) were aneuploid while a minority (22%) were diploid. There was no relationship between ploidy and stage, histologic grade, or the ability to perform optimal cytoreductive surgery. Also, like prior studies using flow cytometry, negative second-look laparotomy and survival were somewhat more common in advanced-stage patients with diploid cancers than in those with aneuploid cancers. We conclude that ploidy of ovarian cancers can be determined using a computerized image analysis system to quantitate feulgen staining of cells in touch imprints. Ploidy is unlikely to play a role in treatment planning for patients with advanced-stage disease. Larger studies of patients with early-stage disease are needed, however, to determine whether ploidy is a more accurate means of predicting which patients are most likely to benefit from adjuvant therapy.

Aneuploidy↗
PubMed1989

Experimental evaluation of a gelatin-coated polyester graft used as an arterial substitute.

Protein coating and endothelial cell preseeding have been proposed and studied as improvements to arterial prostheses. In this paper, an impervious polyester vascular graft which had been coated with cross-linked gelatin was compared to a porous one over a period of up to 8 months in dogs. This evaluation involved in vivo methods using radio tracers to study patency and thrombogenicity and in vitro controls of the healing processes. The main advantages offered by coated grafts over uncoated include the absence of preclotting and better biointegration.

Animals↗
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↗
PubMed1988

Radioresistant pseudo-colony formation in the PHA-leukocyte feeder colony assay.

In the PHA-leukocyte feeder colony assay--a fluid assay on top of an agar underlayer--colonies might not be the product of clonogenic cells but rather from aggregates, as was already shown for hairy cell leukemia (Leukemia Res. 11, 911 (1987)). To study the role of aggregation in this colony assay in other B-cell malignancies, we irradiated cells from B-chronic lymphocytic leukemia, B-non-Hodgkin's lymphoma and multiple myeloma. In nearly all cases, viable "colonies" were seen after irradiation, albeit in lower numbers. These data indicate that in the PHA-leukocyte feeder colony assay, a considerable percentage of colonies from a large variety of B-cell malignancies originate from aggregating rather than from proliferating cells.

B-Lymphocytes↗
PubMed1988

Mitogenic stimulation of malignant B cells CLL: diminished in-vitro stimulation with anti-CR1 antibodies.

Peripheral B lymphocytes of five CLL patients were tested in a radioimmunoassay to determine the density of the C3b receptor (CR1) and the cells were assayed for their ability to mature into IgM secreting cells after in-vitro culture with a combination of Pokeweed Mitogen (PWM) and antibodies directed against CR1. Despite the presence of normal amounts of CR1 on the leukemic B cells, crosslinking of these receptors by anti-CR1 antibodies stimulated only a fraction of the leukemic cell population to differentiate into IgM secreting cells. These results add to the partial functional impairment of CLL-B cells.

Antibodies↗
PubMed1995

Comparison of various in vitro assays for efficacy screening of immunotoxins.

Before using immunotoxins in vivo, their efficacy is evaluated in in vitro assays. In this study we compare six different assays for the evaluation of immunotoxins: protein and DNA synthesis inhibition assay, chromium release assay, cell line colony assay, limiting dilution assay and clonogenic assay. All assays except the chromium release assay show specificity of the immunotoxins in appropriate concentrations. The protein and DNA synthesis inhibition assays are easy to perform and, therefore, suitable for initial screening, while the clonogenic assay seems to be the best one for immunotoxin efficacy determination.

Biological Assay↗
PubMed1991

Binding of the human complement subcomponent C1q to hybrid mouse monoclonal antibodies.

Activation of the classical pathway of the complement system is initiated by the binding of C1q to antibody complexes. Here we evaluated the C1q binding capacity of series of monospecific and bispecific hybrid mouse monoclonal antibodies (mAb) and compared them with parental (conventional) mAb. The hierarchy in C1q binding capacity of the bispecific anti-HuIgA1/HRP mAb with homologous H-H chain combinations (IgG2a-2a, IgG2b-2b and IgG1-1) and the parental anti-HuIgA1 or anti-HRP mAb was identical; IgG2a greater than IgG2b much greater than IgG1. Hybrid IgG1-2a mAb bind intermediate amounts of C1q when compared with the IgG1 and IgG2a parental antibodies. IgG1-2b and IgG1-1 hybrid mAb did not bind any C1q, like the IgG1 mAb. We could not observe any difference in C1q binding efficiency between monovalently bound IgG1-2a, IgG2a-2a and IgG2b-2b anti-HuIgA1 HRP mAb and the bivalently bound IgG1-2a, IgG2a-2a and IgG2b-2b anti-HuIgA1 mAb, respectively. Furthermore, these hybrid ms anti-HuIgA1 and bs anti-HRP/HuIgA1 mAb were able to lyse HuIgA1-coated erythrocytes, in the presence of 50% human serum, as efficiently as their parental counterparts. These data indicate that a simultaneous binding of both F(ab') fragment to antigen is not a necessary prerequisite for binding and activation of C1q.

Antibodies, Monoclonal↗
PubMed1990

Copper complexes of 1,10-phenanthroline and related compounds as superoxide dismutase mimetics.

In a preliminary study we tested CuSO4.5H2O, (Cu(II]2[3,5-diisopropylsalicylate]4.2H2O and a number of copper complexes of substituted 1,10-phenanthrolines for superoxide anion dismutase activity. It appeared that this activity depends on the ligands involved and might be governed by the redox potential of the Cu(I) complex/Cu(II) complex couple. The strong superoxide anion dismutase activity of Cu(II)[DMP]2 complex can be expected considering its high redox potential. Rather surprisingly is the superoxide anion dismutase activity of the Cu(I)[DMP]2 complex since it involves oxidation to Cu(II)[DMP]2 complex. From regression analysis it was established that steric and field effects of the substituents of the investigated phenanthrolines play an important role in SOD activity and therefore it is concluded that complex formation is important for the superoxide dismutase-like activity.

Copper↗
PubMed1987

In vitro effects of thymopentin on the gamma-interferon production by peripheral blood mononuclear cells from normal subjects and from patients with rheumatoid arthritis.

The in vitro production of gamma-interferon (gamma-IFN) by peripheral blood mononuclear cells (MNC) was measured using a specific radioimmunoassay in 16 patients presenting with active rheumatoid arthritis (RA), in 14 patients with inactive disease, and in 36 control subjects (CS). Unstimulated cultures produced undetectable levels of gamma-IFN and did not incorporate tritiated thymidine. In response to phytohemagglutinin (PHA) 0.2 microgram/ml, MNC from active RA produced 9 times less, and under PHA 2.5 micrograms/ml, 4 times less gamma-IFN than did MNC from inactive RA or from CS. The uptake of tritiated thymidine was, however, similar in the 3 groups. In unstimulated cultures of the 3 groups, thymopentin (TP-5), at all concentrations tested, did not influence either the levels of gamma-IFN or the uptake of tritiated thymidine. In the presence of PHA 0.2 microgram/ml and TP-5, lambda-IFN levels were increased in CS, unchanged in inactive RA and reduced in active RA, whereas no changes were observed in the uptake of tritiated thymidine. Our results show that under our experimental conditions, TP-5 was able to increase the levels of gamma-IFN produced by normal MNC in vitro, but could not reverse the profound defect observed in active RA.

Adult↗
PubMed1995

Comparison of DNA content in non-Hodgkin's lymphoma as measured by flow cytometry and cytogenetics.

Specific cytogenetic changes such as t(14;18) and t(8;14) are associated with specific histologic subtypes of non-Hodgkin's lymphoma (NHL) and may predict disease outcome. Nonspecific cytogenetic changes include other structural rearrangements or numerical changes such as monosomies and trisomies, which may cause changes in total cellular DNA content. In many solid tumors, the presence of abnormal DNA content may be predictive of clinical behavior. NHL biopsies, however, contain normal (diploid) as well as abnormal cells, and DNA changes in the peridiploid range are detectable by cytogenetic analysis, but not consistently by flow cytometry. In the present study, we performed flow cytometric and cytogenetic analysis of DNA on biopsies from 129 patients with non-Hodgkin's lymphoma (NHL). Cytogenetic studies were successful on 88 (68%) of the samples. There was 55% concordance between flow cytometric and cytogenetic techniques in detecting aneuploid DNA content, with the majority of discrepancies occurring in the peridiploid range. We also detected six samples which were aneuploid by flow cytometry, but diploid by cytogenetics. We suggest that a reasonable approach to determine DNA content, as it relates to prediction of outcome in NHL, would be to combine data from both of these techniques and analyze the results in terms of ranges of DNA rather than by categorizing as diploid versus aneuploid.

Aneuploidy↗
PubMed1983

Monocyte chemotaxis mediated by formyl-methionyl-leucyl-phenylalanine conjugated with monoclonal antibodies against human ovarian carcinoma.

Availability of a chemically defined chemoattractant (fMLP) and of appropriate monoclonal antibodies may permit local manipulation of the inflammatory response to human tumors. fMLP has been conjugated with two monoclonal antibodies (OC125 and OC133) which react with human ovarian carcinomas. Conjugates retained the ability to bind to a human ovarian carcinoma line (OVCA433) judged by indirect immunofluorescence and by radioimmunoassay. The fMLP conjugate was maximally chemotactic for human blood monocytes and human peritoneal macrophages at protein concentrations of 300-900 micrograms/ml. Conjugates stimulated chemotaxis rather than chemokinesis. After incubation with an fMLP-antibody conjugate, antigen positive OVCA433 cells released chemotactic activity and attracted monocytes in vitro, whereas an antigen-negative ovarian cell line failed to do so. As monocytes can be important effectors of antibody dependent cell mediated cytoxicity, fMLP conjugates might increase monocyte concentrations at tumor sites and potentiate serotherapy for certain human neoplasms.

Antibodies, Monoclonal↗