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Biomedical subjects

J Lindgren

Publications and source records attributed to J Lindgren.

At least 37 records · Page 2Linked to original sources

Monoclonal antibody-defined antigens of human prostate cancer cell line PC3.

Over 600 hybridomas were derived from the immunization of mice with live cells and aqueous extracts of the human prostatic carcinoma cell line PC3. A total of 26 hybridomas with restricted reactivities were selected, subcloned and antibodies tested on a variety of tumor and normal cells. Seven monoclonal antibodies showed reactivity for prostate cancer and other tumor cell lines, including breast carcinomas. Three of the antibodies obtained after immunization with live cells reacted with live cells only and three of the four antibodies obtained after immunization with cell extract reacted with cell extracts and spent culture media. The fourth antibody in the latter group was reactive only in the immunoperoxidase staining assay. Antibody PrS5 recognized a 90,000 molecular weight molecule from 125I-surface-labeled cells in immunoprecipitation analysis. Antibodies PrE3 and PrD8 detected a nonacid glycolipid pentasaccharide from PC3 cells and meconium, and a glycoprotein of 115,000 molecular weight from 125I-surface-labeled red blood cells. The similar patterns of reactivity in RIAs and antigen analysis suggest that antibodies PrE3 and PrD8 recognize the same molecule. The results emphasize the usefulness of immunohistochemistry in the testing of monoclonal antibodies and the impact of the form in which the antigen is presented on the resultant antibody specificity.

Animals↗

Gastrointestinal cancer-associated antigen CA 19-9 in histological specimens of pancreatic tumours and pancreatitis.

The expression of the gastrointestinal cancer associated antigen CA 19-9, defined by the monoclonal antibody 1116 NS 19-9, was studied by immunoperoxidase staining in routine formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and from benign and malignant pancreatic neoplasms. The formalin-fixed specimens were treated with pepsin, which enhanced the staining intensity. Eighty-five per cent of well to moderately differentiated adenocarcinomas were positive. The staining was most intense in the apical border of cells lining the lumina of malignant glands, and in mucus inside the lumina, but cytoplasmic staining was also seen. In poorly differentiated adenocarcinomas the number of positive cells was smaller and in anaplastic carcinomas only occasional cells were stained. All mucinous cystadenomas and cystadenocarcinomas stained intensely, whereas serous cystadenomas, and all benign and malignant islet cell tumours were negative. Ducts in chronic pancreatitis and in normal pancreata were positive in 96% and 79%, respectively, but the staining was focal and usually weaker than in carcinomas. In acute pancreatitis (92% positive) the staining was more intense, and the CA 19-9 expression was seen predominantly in small terminal ducts and in centroacinar cells. There was an apparent correlation between the degree of differentiation of the ductal adenocarcinomas and the expression of CA 19-9, whereas the correlation between tissue expression and serum levels of CA 19-9 was poor.

Adenocarcinoma↗

Sialylated Lewis determinant CA 19-9 in benign and malignant gastric tissue.

The expression of the carbohydrate antigen CA 19-9 in human gastric mucosa was studied by using the monoclonal 1116 NS 19-9 antibody, immunohistochemical ABC staining technique and formalin-fixed, paraffin-embedded biopsy specimens. Among 26 gastric carcinoma (GCA) patients CA 19-9 antigen was found in 16 patients (62%). The antigen was also found in 10 (48%) out of 21 non-cancer patients who had benign gastric ulcer and in 9 (12%) out of 74 non-ulcer, non-cancer patients. In non-cancerous mucosa, the CA 19-9 antigen was localized in the surface epithelium (foveolar type of staining) and/or in goblet cells and sometimes in absorptive epithelium of metaplastic intestinal glands (goblet cell type). The foveolar type but not the goblet cell type was related to the nonsecretor status of the subject, to Le positivity and to anti-H negativity of the gastric surface epithelium. It is concluded that, although being commonly present in GCA tissue, the expression of the antigen in benign gastric tissue is too common to advocate the practical value of CA 19-9 in predicting malignant gastric lesions in immunohistochemistry.

Antigens, Neoplasm↗

Carcinoembryonic antigen (CEA) and gastrointestinal cancer associated antigen CA 19-9 in bronchioloalveolar carcinomas and pulmonary adenocarcinomas.

The concentrations of carcinoembryonic antigen (CEA) and the gastrointestinal cancer associated antigen CA 19-9 were studied by radioimmunoassay in serum samples from patients with malignant and benign pulmonary tumours. Elevated levels of either markers were found in 14% of patients with malignant tumours and in none of the cases with benign lesions. Following removal of the tumour, a decline in high CA 19-9 levels was found. The advanced tumours produced the highest serum CA 19-9 concentrations but elevated values were also found in small bronchioloalveolar carcinomas and pulmonary adenocarcinomas. Immunohistochemical staining for CEA and CA 19-9 was performed on routine histopathological specimens. About half of the cases of bronchioloalveolar carcinomas and pulmonary adenocarcinomas were CA 19-9 positive and about 90% were CEA positive. No correlation between intensity of tissue expression and serum levels of CA 19-9 could be demonstrated. However, the bronchioloalveolar carcinomas and pulmonary adenocarcinomas which produced high serum levels of CA 19-9 also stained positively.

Adenocarcinoma↗

Prognostic significance of tissue carcinoembryonic antigen in mild dysplasia of the uterine cervix.

Two murine monoclonal antibodies to carcinoembryonic antigen (CEA) were used to detect CEA by the immunoperoxidase staining method in mild dysplasia of the uterine cervix in order to evaluate the prognostic significance of the expression of this antigen. The high affinity antibodies (Ha) detected CEA determinants in 53% of the 47 lesions studied while 40% of the epithelial changes were positive with the low affinity antibodies (La). Ha antibodies stained ten out of the 16 progressive lesions (62%), while La antibodies detected CEA determinants in 38% of these. Forty-eight per cent of the 23 regressive lesions were CEA positive with Ha and 39% with La antibodies respectively. The eight persistent lesions expressed CEA equally frequently (50%) with both antibodies. The results indicate that tissue CEA in patients with mild cervical dysplasia does not reflect malignant potential.

Adult↗

Shared antigens of human prostate cancer cell lines as defined by monoclonal antibodies.

Eight monoclonal antibodies (MAbs) raised against human prostate cancer cell lines are described. One MAb was derived from the fusion of mouse myeloma P3x63Ag8-653 cells with spleen cells of mice immunized with DU145 prostate cancer cells. The other seven were from the fusion of myeloma lines P3x63Ag8-653 or SP2/0 with spleen cells of mice immunized with PC3, DU145 and 1013L prostate cancer cells. All of the antibodies also reacted with cell lines of other human cancer types, especially carcinomas. Immunoperoxidase staining on fixed tissue revealed strong reactivity only with antibody PrN10. Seven other antibodies seemed to bind to cell surface-associated (glyco)proteins. Antibodies PrL22 and PrO11 showed similar reactivity in radioimmunoassay, and immunoprecipitated a 160 kD molecular weight polypeptide from [125I]lactoperoxidase-labeled cells. Antibodies PrHk an PrQ12 bound to molecules with apparent MW of 115 kD and 100 kD, respectively; antibodies PrM24 and PrP14 revealed a more complex picture in immunoprecipitation of surface-labeled cells.

Antibodies, Monoclonal↗

Characterization of gastrointestinal tumor-associated carcinoembryonic antigen-related antigens defined by monoclonal antibodies.

Four major carcinoembryonic antigen-related glycopeptides (Mr 180,000, 160,000, 50,000, and 40,000) were detected in SW948 colon carcinoma cells and in colon adenocarcinoma tissue using a monoclonal antibody (C(4)20-32) generated by immunizing mice with SW1222 human colon carcinoma cells. Only the Mr 50,000 polypeptide was immunoprecipitated from normal colon mucosa by this antibody. Binding studies using other monoclonal antibodies and lectins indicated the different epitopes and carbohydrate attachment sites on each of the four polypeptides. Only monoclonal antibody C(4)20-32 recognized a common determinant on all four polypeptides which was revealed by its reactivity with each affinity-purified component.

Adenocarcinoma↗

Detection of carcinoembryonic antigen and related antigens in sera of patients with gastrointestinal tumors using monoclonal antibodies in double-determinant radioimmunoassays.

Of 14 monoclonal antibodies produced in six different laboratories, 13 bound to purified preparations of carcinoembryonic antigen (CEA). All antibodies reacted to spent medium of colorectal carcinoma cell lines. Competitive binding studies indicated that 12 different antigenic determinants representing six different groups were detected on the CEA molecule(s). Six antibodies were used in double determinant radioimmunoassays (RIA) to detect CEA and CEA-related antigens in sera of 311 patients with various gastrointestinal diseases and of normal donors. None of up to 115 sera of healthy donors had elevated antigen levels with four out of the six monoclonal antibodies tested, whereas up to 9% of sera showed elevated antigen levels when tested with two antibodies. Between 1.4% and 4.4% of sera from patients with inflammatory and benign neoplastic diseases of the gastrointestinal tract were positive. Antigen levels were elevated in 56 to 75% (depending on antibody used) of sera from patients with advanced gastrointestinal tumors. These preliminary results indicate that double-determinant immunoassays with a panel of monoclonal antibodies might improve conventional CEA assays by reducing the number of false positive sera detected by polyclonal sera in patients with benign inflammatory bowel diseases.

Antibodies, Monoclonal↗

Immunoperoxidase staining of carcinoembryonic antigen with monoclonal antibodies in adenocarcinoma of the colon.

Mouse monoclonal antibodies to carcinoembryogenic antigen (CEA) obtained by the somatic cell hybridization technique of Köhler and Milstein were used in a modified enzyme bridge immunoperoxidase staining method. Both high and low affinity antibodies were tested and their staining properties compared with those of a commercial polyvalent rabbit antiserum. The staining pattern of neoplastic epithelial cells in all seven antibodies in samples of primary adenocarcinoma of the colon was similar, indicating that no gross differences were found in the exposure of the different antigenic determinants of CEA in formalin fixed tissue. The background staining of the monoclonal antibodies are negligible. It is concluded that monoclonal antibodies are superior to conventional antisera in immunoperoxidase staining of CEA.

Adenocarcinoma↗

Monoclonal antibodies to carcinoembryonic antigen (CEA): characterization and use in a radioimmunoassay for CEA.

Fusion of immune spleen cells of mice immunized with CEA with a mouse myeloma cell line resulted in several hybrid cell lines secreting antibodies to CEA as tested by radio-immunoassay. Four of these were cloned by limiting dilution and large amounts of anti-CEA antibodies were produced by growing the anti-CEA-producing cell clones intraperitoneally in mice and collecting the ascites fluids formed. Ascites fluids containing antibodies with both high and low affinity were obtained. The antibody having the highest affinity was shown to be specific to CEA, whereas one antibody showed cross-reaction with the normal cross-reacting antigen (NCA). The establishment of a competitive-inhibition doubleantibody radio-immunoassad with high sensitivity and specificity using mouse monoclonal antibodies is described.

Animals↗

Alpha fetoprotein levels in neonatal hyperbilirubinaemia.

Serum alpha fetoprotein (AFP) levels were studied in 15 neonatally hyperbilirubinaemic children and 15 controls matched for sex and gestational age. All children were born between 38 and 40 weeks of gestation. During the first seven weeks of postnatal life hyperbilirubinaemic children had serum AFP concentrations over twice as high as controls. At the age of 5-7 days the mean (+/- S.E.M.) serum AFP values were 52.4 +/- 5.8 mg/l for hyperbilirubinaemic children and 24.8 +/- 4.3 mg/l for controls (p less than 0.001). At 20-25 days of age they were 7.28 +/- 1.10 and 2.75 +/- 0.45 mg/l, respectively (p less than 0.001), and at 40-49 days 1.39 +/- 0.21 and 0.46 +/- 0.07 mg/l (p less than 0.001). However, no correlation was found between serum bilirubin and AFP concentrations in hyperbilirubinaemic children.

Age Factors↗

Carcinoembryonic antigen in fetal tissues and in material serum.

The occurrence of CEA was extensively adsorbed to eliminate cross-reactions with CEA-related antigens. After the first trimester of pregnancy CEA was found throughout the gastrointestinal tract by both techniques, whereas the other fetal tissues and fetal serum did not contain detectable amounts of CEA. The CEA-level of all 69 sera of pregnant women was below 2.5 ng/ml. The excretory nature of CEA was suggested by the localization of CEA in the luminal border of the alimentary tract and by the finding that the CEA concentration in the content of fetal gastrointestinal canal was higher than in the surrounding tissue. Gel filtration on Sepharose 4B showed that molecular weight of CEA immunoreactive material of the fetal gut was similar to that of CEA purified from colon cancer, but a minor component with a higher molecular weight was eluted in the void volume. When tested in radioimmunoassay, the CEA immunoreactive material in both peaks gave an inhibition curve parallel to that of purified CEA.

Carcinoembryonic Antigen↗

Distinction between endocervical and endometrial adenocarcinoma with immunoperoxidase staining of carcinoembryonic antigen in routine histological tissue specimens.

The differential diagnosis of endocervical and endometrial adenocarcinomas can be improved by the demonstration of carcinoembryonic antigen (CEA) in tissue by means of immunoperoxidase staining. Tissue from 131 (80%) of 163 patients with endocervical adenocarcinoma but only 11 (8%) of 137 patients with endometrial adenocarcinoma was CEA-positive. The commonest exceptions were endocervical mesonephroid adenocarcinomas (which were CEA-negative) and endometrial adenosquamous carcinomas (which were CEA-positive). After exclusion of these on simple morphological criteria, 86 of 107 endocervical adenocarcinomas (80%) were CEA-positive, and all 122 endometrial adenocarcinomas were CEA-negative. The remarkable difference in the expression of CEA between endocervical and endometrial adenocarcinomas suggests a novel application of immunohistochemistry in routine clinical practice.

Adenocarcinoma↗

Tissue CEA in premalignant epithelial lesions and epidermoid carcinoma of the uterine cervix: prognostic significance.

Carcinoembryonic antigen (CEA) was studied by the indirect triple-bridge immunoperoxidase method in formalin-fixed paraffin-embedded tissue specimens from 191 patients with premalignant epithelial lesions or epidermoid carcinoma of the uterine cervix treated 12 years ago. The frequency of tissue CEA positivity was found to increase with advancing clinical disease in the following manner: mild dysplasia, 25%; severe dysplasia, 37%; carcinoma in situ, 60%; invasive carcinoma stage I, 60%; stage IIa, 65%; stage IIb, 80%; and stages III and IV, 69%. The prognostic significance of the tissue CEA positivity was studied in two groups of patients formed on the basis of clinical spread and treatment of the disease. The first group of 60 patients with stage I and IIa cancers had undergone radical surgery. The second group of 44 patients with more advanced carcinoma had been treated by radiotherapy alone. No significant difference in the survival rates was observed in either group between patients with CEA-positive and CEA-negative tumours. In the light of the absence of CEA from normal cervical epithelium, the increasing occurrence of CEA from premalignant lesions to advancing malignant growth suggests that CEA reflects an aggressive potential in premalignant lesions. However, the survival data on patients with CEA-positive and -negative invasive carcinomas suggest that CEA-positive cancers are not more malignant than CEA-negative cancers.

Carcinoembryonic Antigen↗

Carcinoembryonic antigen in endoscopic brush specimens from benign and malignant gastric lesions.

The measurement of carcinoembryonic antigen (CEA) in serum and endoscopic brush specimens was evaluated for the differential diagnosis of malignant and nonmalignant gastric disease. Brush specimens were studied from 33 patients with gastric cancer and 36 patients with benign gastric lesions or apparently normal gastric mucosa. Demonstrable CEA immunoreactivity was found by radioimmunoassay in brush specimens from 24/33 cancer patients (73%) and from 23/36 patients with benign lesions (64%). Patients with CEA+ tissue in the immunoperoxidase test had somewhat higher CEA concentrations in the brush specimens than cases with CEA- biopsy tissue, although overlap was considerable. Thirty-five per cent of cancer patients had both a positive tissue CEA reaction and a CEA/DNA ratio greater than 10 ng/micrograms, whilst patients with benign lesions had only 15% of positives by these criteria (0.01 greater than P greater than 0.001). The serum CEA concentration was above the upper normal level of 5 ng/ml in 2/39 patients, both of whom had gastric cancer. The CEA immunoreactive material from benign and malignant lesions eluted in gel filtration on Sephadex G-200 in the same volume as CEA purified from liver metastases of cancer of the colon, showing that a glycoprotein sharing immunological and physicochemical properties with CEA is present both in malignant and nonmalignant lesions of the gastric mucosa, and that there is considerable overlapping in the amount of CEA. The estimation of CEA in gastric-brush specimens is therefore of limited value in the differential diagnosis of benign and malignant gastric lesions.

Adult↗