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F A Anderer

Publications and source records attributed to F A Anderer.

At least 73 records · Page 4Linked to original sources

Preferential induction of cell-mediated immunity by chemically modified carcinoembryonic antigen.

Modification of carcinoembryonic antigen (CEA) with various chemicals was investigated. Modification of CEA with dimethylsulfate or acetic anhydride resulted in derivatives which preferentially induced delayed-type hypersensitivity (DTH) against native CEA in mice. The strength of the DTH reaction was dependent on the number and chemical nature of modifying groups as well as on the immunizing dose. The strongest DTH reaction without detectable formation of antibodies was achieved by low dose immunization using heavily methylated CEA.

Acetates↗

Cell adhesion-dependent differences in endogenous protein phosphorylation on the surface of various cell lines.

Endogenous phosphorylation of intact cells was studied with four mouse, hamster and human cell lines using [gamma-32P]ATP and [gamma-32P]GTP as exogenous substrates. With all four cell lines distinct differences in the phosphoprotein patterns could be demonstrated for cells grown in suspension culture compared to cells grown in monolayers. Two major, apparently ubiquitous phosphoproteins with molecular weights of 135 000 (128 000 in HeLa cells) and 105 000, representing up to 60% of total phosphorylation, were phosphorylated only in cells grown in suspension. These phosphoproteins and the kinase(s) were located on the surface of the suspension cells. Evidence showed that phosphorylation was apparently not a true endogenous reaction, that rather it occurred by cell-cell collision, showing exponentially increasing 32P incorporation with increasing cell population density. Phosphorylation of pp135 and pp105 was established with ATP as well as with GTP and was not dependent on cyclic nucleotides cyclic AMP, cyclic GMP and cyclic CMP. The substrate-attached cells of all four cell lines have protein kinases on the cell surface. The lack of pp135 and pp105 phosphorylation may be due to the fact that these phosphoproteins are not expressed at all on the surface of substrate-attached cells or that these phosphoproteins are already fully phosphorylated.

Adenosine Triphosphate↗

The formation of sphingomyelin from phosphatidylcholine in plasma membrane preparations from mouse fibroblasts.

The enzymatic formation of radioactive sphingomyelin from [14C]choline-labeled phosphatidylcholine was demonstrated to reside exclusively in the plasma membrane fraction of mouse fibroblasts. This activity has several properties in common with the phosphatidylcholine ceramide phosphocholine transferase of mouse liver microsomes. The enzyme has little if any phospholipase C activity and isotope dilution experiments suggest that phosphatidylcholine is the substrate rather than it is converted to CDP choline, phosphocholine, free choline or glycerophosphocholine prior to the transfer reaction. The activity is stimulated by the addition of bovine serum albumin and MnCl2 to the incubation mixtures. The plasma membrane localization of the enzyme suggests that it may have a central role in the biosynthetic pathways for sphingomyelin in mouse fibroblasts.

Animals↗

Stimulation of DNA polymerase alpha by a nuclear DNA/protein complex.

A nuclear DNA complex containing DNA polymerase and SV40 T-antigen was isolated from nuclei of SV40-transformed mouse fibroblasts. DNA polymerase could be separated from the complex. The remaining DNA/T-antigen-containing complex stimulated DNA polymerase alpha activity about 10-fold. The complex contained 4 major proteins with molecular weights of 46, 54, 76, and 94 kilo-dalton (KD). The stimulation activity was retained by protein A-Sepharose loaded with specific IgG from SV40-tumor bearer serum, or from antisera against the 94 KD and 76 KD components and was partially inhibited in the presence of these antisera. The stimulation activity was completely abolished by treatment of the complex with trypsin or DNase I.

Animals↗

Prognostic value of preoperative serum CEA level compared to clinical staging. I. Colorectal carcinoma.

In a clinical investigation of observed postoperative survival, 563 patients have been registered for primary surgical treatment of colorectal cancer since 1974. The potential prognostic factors examined within the first days of hospitalization for primary resection included age of the patients, operability, location of the tumour, tumour extension and the preoperative serum CEA level. Statistical treatment of the data revealed that each of the clinical parameters except tumour location covers ranges associated with highly significant differences in survival of the patients. The preoperative serum CEA level gave prognostic information in addition to operability or tumour extension. The prognostic significance of the preoperative CEA level was still evident when selected subgroups of patients with distinct resectability and tumour extension were examined. The results indicate that the preoperative serum CEA level is an independent prognostic parameter.

Age Factors↗

Comparison of serum beta 2-microglobulin and carcinoembryonic antigen (CEA) in the follow-up of breast cancer patients.

Using commercially available radioimmune test kits, serial determinations of serum beta 2-microglobulin and CEA were performed in 337 patients, who had been treated for breast cancer by modified radical mastectomy and radiotherapy. The pre-therapeutic data indicated a higher incidence of pathological beta 2-microglobulin and CEA levels in patients with distant metastases than in patients with localized disease. However, this finding did not allow the conclusion of a direct complementarity of beta 2-microglobulin and CEA as tumour markers, since the group of patients with distant metastasis contained a high percentage of elderly patients who generally can be expected to have elevated beta 2-microglobulin serum concentrations. Therefore, the correlation of the clinical course of malignant disease and the incidence of relapses with the changes of serum beta 2-microglobulin and CEA concentrations was examined during the post-treatment surveillance: 7/9 cases (78%) with local recurrence and 46/73 cases (63%) with distant spread of disease were not indicated in the beta 2-microglobulin follow-up by pathologic serum concentrations, whereas in the CEA follow-up only 1/9 and 2/73 false negative indications were registered. The poor correlation suggests that serum beta 2-microglobulin is not directly tumour associated in breast cancer and does not fulfill the criteria of a tumour marker.

Adult↗

Is serum beta 2-microglobulin a tumor marker in gastrointestinal cancer?

Serial determinations of serum beta 2-microglobulin (beta 2m) and carcinoembryogenic antigen (CEA) were performed in 314 patients with histologically confirmed gastrointestinal cancer. The data were correlated with a set of clinical parameters. Pre-operative serum beta 2m levels did not discriminate different classes of tumor extension nor different stages of resectability of tumors in contrast to CEA. During post-operative surveillance the correlation of the time courses of serum beta 2m and CEA with the clinical course of malignant disease was studied in a selected group of 165 patients with resected primary carcinoma of the gastrointestinal tract. During the follow-up 74/165 patients showed disease progression or recurrence. In the beta 2m follow-up 66% false negative indications (49/74) of malignant disease were observed, whereas in the CEA follow-up it was 5% (4/74). The ratio of correct positive/false positive indications was 25/10 in the beta 2m follow-up and 70/10 in the CEA follow-up. The data indicate that the formation of serum beta 2m is not directly tumor associated in gastrointestinal cancer.

Adenocarcinoma↗

[Relapse prognosis for patients with adenocarcinoma of the gastrointestinal tract on the basis of carcinoembryonic antigen (CEA) and its circulating immune complexes (author's transl)].

CEA immune complexes and free CEA were routinely determined in sera of 350 patients with adenocarcinoma of the gastrointestinal tract preoperatively and during a 2-year surveillance period. We could detect circulating CEA immune complexes preoperatively in 25% of our patients. The appearance of CEA immune complexes prove to be a useful prognostic marker with respect to tumor extension since 72/86 patients with CEA immune complexes showed metastasis at the primary resection. The postoperative appearance of CEA immune complexes could be used as an additional parameter for the diagnosis of the relapse; 32/60 patients with a relapse developed CEA immune complexes during the period of surveillance. All patients with localized disease recurrence were found to be free of CEA immune complexes. Detection of CEA immune complexes, however, coincided always with the clinical diagnosis of distant spread of disease. This diagnosis was always preceded by an increase of free CEA and/or CEA immune complexes. In 50/60 patients the relapse could only be demonstrated by clinical methods since these patients stayed CEA-negative throughout the surveillance period.

Adenocarcinoma↗

Are circulating CEA immune complexes a prognostic marker in patients with carcinoma of the gastrointestinal tract?

CEA immune complexes and free CEA were determined to 363 patients with histologically confirmed adenocarcinoma of the gastrointestinal tract before surgery and in a post-operative follow-up. Circulating CEA immune complexes (CEA-IC) could be detected preoperatively in 89 patients. Incidence of CEA-IC increased with increasing tumour extension; 72/89 patients with CEA-IC showed already metastatic disease progression, 40/89 had nonresectable tumours. Patients with preoperative CEA-IC had a poorer prognosis than patients without CEA-IC but with high levels of free CEA, or CEA-negative patients. The appearance of CEA-IC with consecutive increases in the postoperative follow-up indicated disease recurrence. In 32/55 relapse cases, circulating CEA-IC were detected postoperatively, all 32 cases developing metastatic spread of disease.

Adenocarcinoma↗

Carcinoembryonic antigen (CEA) measurements as an aid to management of patients with lung cancer treated by radiotherapy.

Serial CEA measurements performed in 102 lung cancer patients during and after radiotherapy and chemotherapy correlated well with the course of disease. CEA levels above 10 ng CEA/ml prior to radiotherapy signaled metastatic spread even when this was not evident from clinical staging of the patient (TNM). This finding contributed to the early adoption of radiotherapy in favor of palliative treatment. Alterations of the CEA concentration during therapy could be used for monitoring the efficiency of treatment. Increasing CEA levels always signaled disease progression, decreasing CEA levels were found to be associated with improvement. In the posttreatment follow-up, increasing CEA levels were always reliable predictors of recurrent disease. Slope analysis of the posttreatment CEA time courses discriminated bone and/or liver metastases with a slope greater than 0.5 ng/ml/10 days from local recurrences, lymph node, lung and brain metastases with slope values less than 0.5 ng/ml/10 days.

Carcinoembryonic Antigen↗

Serial carcinoembryonic antigen (CEA) determinations in the management of patients with breast cancer.

Serial CEA determination have been performed in 335 patients with operable breast cancer who received radiotherapy and then were the subjects of a long-term follow-up study. Tumor extension was staged by the surgeon according to the TNM classification. Elevated pretreatment CEA levels (greater than 10 ng/ml) indicated metastatic spread even when this was not evident from the original TNM classification. Elevated CEA levels of greater than 4 ng/ml also led to a reevaluation of patients and in 20% metastatic spread was found. Therapy was adapted when patients had demonstrable distant spread. Response to treatment could be correlated with decreasing CEA levels while increasing CEA levels were generally found when disease progression was observed. During long-term CEA follow-up, 80% of recurrent cancers were signaled by increasing CEA levels. A mean lead time of 4.8 months was calculated for the initial CEA increase before clinical confirmation. Slope analysis of the posttreatment CEA time course represented a numerical parameter which was characteristic for osseous and/or liver metastases when values of greater than 0.5 ng/ml/10 days were recorded. Soft tissue, lymph node, lung and brain metastases showed generally a slope value of less than 0.5 ng/ml/10 days.

Adult↗

[Prognostic value of circulating immune complexes of carcinoembryonic antigen (CEA) in patients with adenocarcinoma of the gastrointestinal tract (author's transl)].

CEA immune complexes and unbound CEA were preoperatively determined in 350 patients with histologically confirmed adenocarcinoma of the gastrointestinal tract. Circulating CEA immune complexes could be detected in 86 patients (25%) where an increase of tumor extension according to TNM classification was concomitant with an increasing percentage of patients with CEA immune complexes. 74/86 patients showed simultaneously pathological concentrations of unbound CEA. During postoperative surveillance the determinations of circulating CEA immune complexes could be used as prognostic criteria. In 30/50 patients with recurrent cancer CEA immune complexes were detected latest at the time of clinical diagnosis. Appearance of CEA immune complexes might contribute to characterization of the immune status of the patients. Some of the patients with widespread tumors exhibited a rapid increase of CEA immune complexes a few months before exitus (44% of the patients). Before exitus 13% of the patients again showed a greatly decreased concentration of CEA-immune complexes.

Adenocarcinoma↗

Serial CEA determinations as an aid in postoperative therapy management of patients with early breast cancer.

Serial CEA measurements as an aid in routine clinical diagnostic methods was investigated in 69 women with early breast cancer. In 14/69 cases detection of metastatic spread on the basis of elevated pretreatment CEA levels together with clinical aspects led to early adaption of treatment. 27 patients had no metastatic spread (group I) and 28 patients had lymph node metastases (group II). During the follow-up of 55 patients of group I and II, disease progression was signaled by rising CEA values in 10/11 cases with a lead time of up to 8 months before a positive clinical diagnosis was possible. For another 6 patients disease progression has to be expected because of consecutively increasing CEA levels. Patients of group II exhibited a higher frequency of relapses compared to group I patients. Decreasing CEA levels could be correlated in our study with patients who were considered to have had a successful treatment by local radiotherapy and who showed no recurrence during surveillance period along with normal CEA values. About 30% of the patients, however, showed essentially unchanged CEA levels mostly in the normal range.

Adult↗

Circulating carcinoembryonic antigen immune complexes in sera of patients with carcinomata of the gastrointestinal tract.

The sera of patients with histologically proven carcinomata of the gastrointestinal tract were fractionated by gel filtration and the fractions assayed for the presence of free carcinoembryonic antigen (CEA) binding immunoglobulins and CEA immune complexes by radioimmuno-double-diffusion, using 125I-CEA as a marker. In eleven out of thirteen cases with disease recurrence, the presence of CEA-IgM complexes was observed, and in three out of thirteen cases the presence of CEA-IgG complexes, could be demonstrated. Free CEA-binding immunoglobulins could not be detected.

Adenocarcinoma↗

An approach to the routine estimation of circulating carcinoembryonic antigen immune complexes in patients with carcinomata of the gastrointestinal tract.

The carcinoembryonic antigen (CEA) distribution obtained after fractionation of thirty sera of patients with gastrointestinal tumours by gel filtration in Sephadex G200 was compared with that resulting from extraction of the sera with perchloric acid. In all cases gel filtration yielded a fraction of free CEA and in twenty-three cases an additional fraction of CEA immune complexes. The amounts of free CEA corresponded fairly well to the fractions of CEA which could be extracted by perchloric acid. The CEA content of the fraction containing CEA immune complexes was comparable to the CEA content of the perchloric acid precipitates. The presence of CEA immune complexes in the perchloric acid precipitates could be demonstrated by gel filtration under dissociating andnon-dissociating conditions and after pre-incubation with 125I-CEA by radioimmuno-double-diffusion using monospecific rabbit antisera against human IgM and IgG.

Adenocarcinoma↗

Carcinoembryonic antigen follow-up and selection of patients for second-look operation in management of gastrointestinal carcinoma.

A long-term postoperative carcinoembryonic antigen (CEA) follow-up study is carried out with patients having undergone primary resection of histologically proved adenocarcinomas of the gastrointestinal tract. Up to now, 122 patients who underwent curative resections, as judged from the situs and the results of histologic examinations, were followed up for tumor recurrence by computerized CEA surveillance diagrams and clinical diagnostic methods. In the cases of tumor recurrence the rise of the CEA level preceded a positive clinical diagnosis by a mean of 4 months. On the basis of the CEA time course, we selected 28 patients for second-look surgery. In all cases proof of recurrence of the disease was obtained. A local recurrence correlating with a slow CEA rise was generally resectable, metastases correlating with a rapid CEA rise were only in some cases resectable, provided that second-look surgery was carried out without delay.

Adenocarcinoma↗