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A Thor

Publications and source records attributed to A Thor.

72 records · Page 4Linked to original sources
PubMed1986

Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3.

Murine monoclonal antibody B72.3, prepared against a membrane-enriched extract of human metastatic carcinoma, was reacted with a spectrum of adult and fetal human tissues using avidin-biotin-complex immunohistochemical techniques to evaluate the expression of the reactive tumor associated glycoprotein (TAG)-72 antigen. TAG-72 was shown to be expressed in several epithelial-derived cancers including 94% of colonic adenocarcinomas, 84% of invasive ductal carcinomas of the breast, 96% of non-small cell lung carcinomas, 100% of common epithelial ovarian carcinomas, as well as the majority of pancreatic, gastric, and esophageal cancers evaluated. TAG-72 expression was not observed, however, in tumors of neural, hematopoietic, or sarcomatous derivation, suggesting that the TAG-72 antigen is "pancarcinoma" in nature. Appreciable monoclonal antibody B72.3 reactivity was generally not observed in adult normal tissues, with limited reactivity noted in a few benign lesions of the breast and colon. TAG-72 antigen expression was detected, however, in fetal colon, stomach, and esophagus, thus defining TAG-72 as an oncofetal antigen. TAG-72 has previously been shown to be distinct from carcinoembryonic antigen and other tumor associated antigens. The pancarcinoma distribution and lack of significant reactivity with normal adult tissues of monoclonal antibody B72.3 suggest its potential diagnostic and therapeutic utility for human carcinomas.

Animals↗
PubMed1986

Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3.

Murine IgG1 monoclonal antibody (MoAb) B72.3, reactive with a high molecular weight glycoprotein complex [designated tumor-associated glycoprotein-72 (TAG-72)] was shown, with the use of the avidin-biotin-complex-immunoperoxidase technique and surgically resected tissues, to be reactive with a variety of histologic tumor types. TAG-72 is expressed in at least 5% (and up to 100%) of the malignant epithelial cells in 77% (n = 52) of human primary cancers and 71% (n = 31) of metastatic ovarian cancers of the common "epithelia" histologic category. Of these, several histologic types, including serous and mucinous cystadenocarcinomas, undifferentiated carcinomas, and less common types of ovarian carcinoma, were all shown to express TAG-72. In contrast, normal ovarian tissues and 26 of 27 benign ovarian tumors of various histologic types failed to express similar levels of TAG-72. Of interest is the 1 benign tumor that demonstrated unusual glandular complexity, as well as 3 tumors designated as borderline malignancy, that contained elevated TAG-72 expression. MoAb B72.3 also was used successfully to detect ovarian carcinoma cells in 28 cytologic preparations of human serous effusions and peritoneal washings. The reactivity of MoAb B72.3 was shown to be distinct from that of MoAb OC125 and an anti-CEA MoAb B1.1. The potential applications of MoAb B72.3 in the study of human ovarian cancer cell populations, as well as in several aspects of the management of human ovarian cancer, are discussed.

Animals↗
PubMed1986

Histologic demonstration of antigens reactive with anti-p21 ras monoclonal antibody (RAP-5) in human stomach cancers.

The immunohistochemical reactivity of RAP-5, a monoclonal antibody (MoAb) raised against a synthetic peptide corresponding to positions 10-17 of the ras gene product from T24 bladder carcinoma, was studied in 96 surgically resected stomach cancers of humans. The cytoplasm of cancer cells in 65 cases (68%) was positively stained with MoAb RAP-5, although the staining was heterogeneous among cancer cells. There was no definite correlation between depth of tumor invasion and reactivity to MoAb RAP-5. Cancer cells of poorly differentiated tumors showed a tendency to react less frequently and less intensely to MoAb RAP-5. In nontumorous gastric mucosa, parietal cells and some portions of intestinal metaplasia were stained with MoAb RAP-5. These findings suggest an increased expression of the ras gene product (p21) in about two-thirds of gastric adenocarcinomas and in some nonneoplastic gastric epithelial cells.

Antibodies, Monoclonal↗
PubMed1986

Pharmacokinetics of radiolabeled monoclonal antibody B6.2 in patients with metastatic breast cancer.

Thirteen patients with metastatic breast carcinoma were given injections of 50-1593 micrograms of 131I-monoclonal antibody (MAb) B6.2 immunoglobulin G and F(ab')2 for pharmacokinetic evaluation and radioimmunoimaging. Blood clearance of the 131I-MAb-B6.2 was biphasic. The mean half-times (t 1/2 alpha, t 1/2 beta) for the immunoglobulin G were 3.5 +/- 1.7 and 20.9 +/- 11.0 h, respectively. The t 1/2 alpha for the F(ab')2 was 1.7 +/- 1.3 h, and the t 1/2 beta was 31.0 +/- 5.7 h. The percentage of protein bound 131I for the immunoglobulin G and for the F(ab')2 at 72 h was 73.7 +/- 11.4% and 58.2 +/- 14.5%, respectively. In vitro reactivity of MAb B6.2 with granulocytes isolated from normal subjects and patients was demonstrated by cytofluorometric and radioimmunoassays. MAb B6.2 was shown to bind with normal cross-reacting antigen, a cell surface antigen known to be expressed on normal human granulocytes. Reactivity with normal cross-reacting antigen on granulocytes is consistent with the skeletal images obtained during immunoscintigraphy of all 13 patients. A specific tumor image was observed in one patient. No toxicity was encountered. In spite of extensive preclinical data suggesting that 131I-MAb B6.2 would be a useful agent for radioimmunoimaging, the clinical utility of this reagent is probably limited because of the reactivity with granulocytes.

Adult↗
PubMed1985

Tumor-associated antigen TAG-72: correlation of expression in primary and metastatic breast carcinoma lesions.

Variability of tumor-associated antigens among and within human tumor cell groups presents a potential problem in the development and optimization of immunodiagnostic and therapeutic procedures for cancer. We determined the degree of expression of a tumor-associated antigen in the primary and metastatic lesions of 23 patients with infiltrating ductal carcinoma; this was accomplished using monoclonal antibody B72.3, an IgG1 generated against membrane-enriched fractions of human metastatic breast carcinomas and reactive with a 220,000-400,000 d glycoprotein complex, termed TAG-72, and the avidin-biotin complex immunoperoxidase method on fixed tissue sections. Sixteen of the 23 breast carcinomas (70%) demonstrated MAb B72.3 reactivity (range 5% to 100% of tumor cells staining). Reactivity of lymph node metastases was present in 14 of 21 patients (67%). MAb reactivity in metastases to distant sites, including bone, adrenals, liver, skin and effusions, was present in 10 of 18 patients (56%). In one patient, neither the primary carcinoma nor the metastasis to the lymph node demonstrated reactivity. There was a statistically significant positive correlation between MAb B72.3 reactivity in both primary and lymph node metastases (Kendall's Correlation Coefficient = 0.60, p = 0.0006) and between lymph node and distant metastases (Kendall's Correlation Coefficient = 0.48, p = 0.02) of the same patient. No correlation existed between antibody reactivity seen in the primary and that found in the distant lesions of that patient. These studies thus demonstrate that monoclonal antibody B72.3 can detect expression of a tumor-associated antigen in both primary and metastatic infiltrating ductal carcinoma lesions, and may prove valuable in the understanding of tumor biology of metastases and as a means for diagnosing occult disease.

Adult↗
PubMed1985

Monoclonal antibody DF3 correlates with tumor differentiation and hormone receptor status in breast cancer patients.

The murine monoclonal antibody (MAb) designated DF3, reacts with a 300-kd human mammary epithelial antigen which is expressed on apical borders of secretory mammary epithelial cells and in the cytosol of less differentiated malignant cells. Human mammary tumors have been evaluated for the level of DF3 antigen as a correlate to clinicopathologic parameters related to degree of tumor differentiation: nuclear grade (NG), histologic grade (HG), and estrogen receptor status (ER). More DF3 antigen was present in breast carcinomas with NG 1 and 2 as compared to tumors with NG 3 (p = .002). Similarly DF3 antigen presence was greater in HG 1 and 2 tumors than in HG 3 (p less than .001). The results also demonstrate that quantitative differences in the presence of the DF3 differentiation antigen correlate with estrogen receptor status. Twenty-two of 23 ER positive tumors were also DF3 positive. Only 6 of 23 ER negative tumors were reactive to MAb DF3 (p less than .001). There was, however, no correlation between DF3 reactivity and absolute levels of estrogen or progesterone receptor. These findings confirm our hypothesis that MAb DF3 reacts to a differentiation antigen present in some human breast carcinomas. The DF3 antigen phenotype can serve as an independent phenotypic marker with correlations to standard indicators of degree of differentiation and estrogen receptor status of infiltrating ductal carcinomas of the breast, and should thus be evaluated as a prognostic indicator in breast cancer patients. The data also suggests that DF3 histochemistry may be a useful alternative in assessing estrogen receptor status of small breast cancers where there is an insufficient amount of tumor present for biochemical assay of hormone receptor levels.

Antibodies, Monoclonal↗
PubMed1985

Surface expression of tumor-associated antigens in primary cultured human colonic epithelial cells from carcinomas, benign tumors, and normal tissues.

A new method for the analysis of the binding of monoclonal antibodies to cell surface tumor-associated antigens utilizes 1- to 2-day primary cultures of human colonic carcinomas, adenomas, and normal epithelial tissue. The antibodies are added to the live cells which form monolayer epithelial patches of several hundred cells on the surface of the Petri dish by migration in a continuous sheet from a small explant. These epithelial patches are then fixed with methanol and processed in situ using the indirect immunoperoxidase assay. Three monoclonal antibodies (MAbs) prepared against membrane-enriched fractions of human metastatic breast cancer were assayed. MAb B1.1 bound to each of 11 benign and each of 18 malignant colonic tumors tested. MAb B6.2 displayed similar reactivity, binding to each of 7 adenomas and each of 15 carcinomas assayed. Both MAbs also bound to normal colonic epithelial cells in both the live cell studies presented here and in earlier studies (D. Stramignoni et al., Int. J. Cancer, 31: 543-552, 1983). MAb B72.3 bound only to tumor cells and not to normal epithelial cells in the live cell assay. This epitope was rapidly lost in culture. B72.3 reactivity on each of two carcinomas was decreased 9- to 36-fold when primary culture continued for 5-6 days. B72.3 bound to each of 20 tumors (15 carcinomas, 5 adenomas) when the cells were cultured for 1 or 2 days but on only 2 of 8 tumors when the cells were cultured for 3 to 8 days. The B72.3 epitope was more strongly expressed on the live cells in the explant and on those monolayer cells directly adjacent to the explant than on the cells more towards the edges of the patch colony. This implied that the cell flattening which occurred when cells migrated from the explant may have played some role in antigen loss. A very similar fraction of primary cultured carcinoma and adenoma cells bound each MAb, indicating that these MAbs in live cell assay do not distinguish between benign, noninvasive colonic tumors and invasive carcinomas. The live cell assay was compared to the standard assay utilizing sectioned, fixed tumors. In parallel assays of eight tumors the fraction of cells reactive in the indirect immunoperoxidase assay was consistently higher on live cells for each of these MAbs than on fixed tissue. Due to this greater sensitivity the live cell assay was able to detect reactive cells in two cases which were scored as negative (less than 1% positive cells) in the fixed tissue assay.

Adenoma↗
PubMed1985

Definition by monoclonal antibodies of a repertoire of epitopes on carcinoembryonic antigen differentially expressed in human colon carcinomas versus normal adult tissues.

Monoclonal antibodies (MAbs) designated COL-1 through 15 have been generated and characterized and show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues. To prepare the MAbs, mice were immunized with extracts or membrane-enriched fractions of biopsy material from either primary or metastatic colon carcinoma lesions. The fifteen COL MAbs, all of the immunoglobulin G subclasses 1, 2a, or 2b, reacted with purified carcinoembryonic antigen in solid-phase radioimmunoassay and by immunoblotting, but none reacted with human polymorphonuclear leukocytes or certain spleen preparations previously shown to be rich in carcinoembryonic antigen-related or cross-reactive antigens. MAbs COL-1 through 15 could be divided into at least five groups based on their differential range of reactivities to the surface of colon carcinoma cells or other carcinoma cell preparations. The COL MAbs were tested via immunoperoxidase with a wide range of primary and metastatic colon carcinomas, benign or dysplastic colon lesions, and 34 normal adult tissues. With few exceptions, the COL MAbs tested in this manner showed reactivity only to the primary and metastatic colon carcinomas. These studies thus provide a well-characterized repertoire of MAbs that are well suited for potential clinical trials involving the radiolocalization and possibly therapy of human colon carcinoma lesions. The fact that at least five epitopes are being recognized also provides the opportunity for testing the efficacy of cocktails of the COL MAbs toward these goals.

Adult↗
PubMed1985

Expression of laminin receptor in normal and carcinomatous human tissues as defined by a monoclonal antibody.

It has been hypothesized that epithelial and endothelial cells interact with the laminin component of basement membranes via a cell surface laminin receptor molecule. It has also been proposed that the expression of this molecule may be involved in the invasion of carcinoma cells from their tissue of origin and their subsequent penetration through blood vessel basement membranes. We report here the use of a monoclonal antibody, LR-3, to define the expression of laminin receptor in normal, dysplastic, and carcinomatous human tissues. Monoclonal antibody LR-3 is shown by immunoblotting to recognize the Mr 67,000 laminin receptor protein, to bind to the carcinoma cells, and to constitute approximately 0.1% of total cellular protein. Numerous normal human epithelial and endothelial cell types, as well as pulmonary macrophages, are shown to express laminin receptor to varying degrees. Selected human mammary carcinomas and colon carcinomas are shown to bind more monoclonal antibody LR-3 than normal or dysplastic counterparts. A monoclonal antibody to laminin receptor now makes possible the study of the role of laminin receptor in tumor cell metastases and in the differentiation and function of various normal human epithelial and endothelial cell types.

Animals↗
PubMed1985

Use of a monoclonal antibody (B72.3) as an immunocytochemical adjunct to diagnosis of adenocarcinoma in human effusions.

A monoclonal antibody (MAb), designated B72.3, has been generated using membrane-enriched fractions of a metastatic human breast carcinoma as the immunogen. Previous studies have demonstrated that the reactive antigen, a novel Mr 220,000 to 400,000 glycoprotein complex, can be detected in formalin-fixed, paraffin-embedded tissue sections of human breast and colon carcinomas, and not in a variety of normal adult human tissues. In this preliminary study, we report that MAb B72.3 may be used as an adjunct for diagnosis of adenocarcinoma in cytological preparations of human effusions. Using the avidin-biotin complex method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected adenocarcinoma cells in effusions from all of 21 patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions from 24 patients without cancer, or 13 patients with prior or extant cancer in other body sites; moreover, B72.3 showed no reactivity to leukemic or lymphomatous effusions, or apparent mesothelial cells from malignant effusions. MAb B72.3 also detected adenocarcinoma cells in cytological effusion specimens from 12 of 12 patients with adenocarcinoma of the lung and 16 of 16 patients with adenocarcinoma of the ovary. Thus, these data suggest that the immunocytochemical application of MAb B72.3 should now be considered as an adjunct in the discrimination of adenocarcinoma cells from reactive mesothelial cells in the cytological diagnosis of malignant effusions.

Adenocarcinoma↗
PubMed1984

Monoclonal antibodies of predefined specificity detect activated ras gene expression in human mammary and colon carcinomas.

Monoclonal antibodies (MAbs) of predefined specificity have been generated by utilizing a synthetic peptide reflecting amino acid positions 10-17 of the Hu-rasT24 gene product as immunogen. These MAbs, designated RAP-1 through RAP-5 (RA, ras; P, peptide), have been shown to react with the ras gene product p21. Since the Hu-ras reactive determinants (positions 10-17) have been predicted to be within the tertiary structure of the p21 molecule, it was not unexpected that denaturation of cell extracts or tissue sections with Formalin or glutaraldehyde enhanced binding of the RAP MAbs. When paraffin-embedded Formalin-fixed tissue sections and the avidin-biotin complex immunoperoxidase method were used, the RAP MAbs clearly defined enhanced ras p21 expression in the majority of human colon and mammary carcinomas. The majority of all abnormal ducts and lobules from fibroadenoma and fibrocystic disease patients were negative, as were all normal mammary and colonic epithelia examined. The findings reported here form the basis for quantitative radioimmunoassays for a ras translational product and provide a means to evaluate ras p21 expression within individual cells of normal tissues and benign, "premalignant," and malignant lesions.

Adenocarcinoma↗
PubMedDate not supplied

Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases.

DNAS of some human tumours can transform NIH 3T3 fibroblast cells, thus demonstrating the transforming potential of human ras genes (Hu-rasHa, Hu-rasKi, and Hu-rasN, respectively Harvey, Kirsten and neuroblastoma ras genes). Only a small percentage of a given type of human carcinoma, however, scores positive in this assay system. Activation of ras and subsequent transformation of NIH 3T3 cells are either by a point mutation in the ras gene or enhanced expression of the normal, or proto-onc, ras gene. If the transformation of a given human tumour involves the enhanced expression of the normal or cellular ras gene and the resulting gene product, the tumour DNA would probably score negative in the NIH 3T3 transfection assay. In human colon carcinoma, for example, lesions at position 12 of Hu-rasKi have been found. None of nine colon carcinomas obtained at biopsy, however, contain the ras lesion at this position, using a Hu-rasHa probe; one other colon carcinoma does appear to contain amplified proto-onc ras, and other colon carcinomas do have increased levels of ras RNA. There are at least three explanations for these observations. Either very few colon carcinomas contain point-mutated ras, the lesion in the majority of colon carcinomas is at a position other than 12 or ras activation in many colon carcinomas involves the enhanced expression of either the point-mutated or proto-onc form of a ras gene. We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states. Immunohistochemical analyses of individual cells within tissue sections reveal differences in ras p21 expression in colon carcinomas compared with normal colonic epithelium, benign colon tumours and inflammatory or dysplastic colon lesions. Our data suggest that ras p21 expression is correlated with depth of carcinoma within the bowel wall, and is probably a relatively late event in colon carcinogenesis.

Adenoma↗
PubMedDate not supplied

Quantitation of enhanced expression of ras-oncogene product (p21) in childhood renal tumours.

A monoclonal antibody, RAP-5, raised against the 21,000d ras-oncogene product, p21, was used in an immunoperoxidase staining procedure to study the expression of p21 in normal children's and foetal kidneys, pre-malignant lesions and benign and malignant childhood renal tumours with good, moderate or poor prognosis. ras-p21 was expressed in both normal and foetal kidneys but its distribution in renal tumours differed markedly (p less than 0.01). A quantitative liquid competition radioimmunoassay (RIA) was used to determine ras-p21 level in tissue homogenates. The results were expressed as pg of ras-p21 per microgram protein of tissue extract. There were significant differences in the levels of ras-p21 among various renal tissue extracts (p less than 0.05). Generally it emerged that the amount of ras-p21 was greater in both malignant renal tumours and foetal kidneys compared to normal kidneys, pre-malignant lesions and benign renal tumours.

Antibodies, Monoclonal↗
PubMedDate not supplied

Detection of adenocarcinoma in peritoneal washings by staining with monoclonal antibody B72.3.

Peritoneal washings are routinely performed in the staging evaluation of carcinomas of the ovary and in "second-look" explorations; major problems in the evaluation of these specimens continue to be the distinction between atypical mesothelium and adenocarcinoma and the identification in an otherwise inflammatory specimen of rare cells of adenocarcinoma, which may be undetected by the most trained individual. Monoclonal antibody (MAb) B72.3, reactive with an oncofetal, tumor-associated glycoprotein (termed TAG-72; MW greater than 1000 kd) expressed in a variety of epithelial malignancies but not generally expressed in benign or malignant mesothelium, was reacted with sections from the paraffin-embedded cell blocks of 185 peritoneal washings from 180 patients with extant cancer or a prior history of malignancy. One hundred four of the washings were initially interpreted as atypical mesothelium, with no evidence of malignancy; when reacted with MAb B72.3, 6 of these specimens demonstrated groups of metastatic adenocarcinoma cells not appreciated by the usual cytologic criteria. Of the 81 washings interpreted as showing cells of adenocarcinoma, 73 demonstrated expression of TAG-72 from both gynecologic and nongynecologic malignancies. In the remaining 49 cases without an associated malignant process, MAb B72.3 did not stain atypical mesothelium, but did react, however, with benign endometrial cells and müllerian inclusions in two cases. MAb B72.3 may be used as a diagnostic adjunct to the routine cytologic evaluation of malignancy in peritoneal washings; reactivity with MAb B72.3 may indicate the need for further evaluation to define the presence of a malignancy or an advanced cancer.

Adenocarcinoma↗
PubMedDate not supplied

Spermatic granuloma. Diagnosis by fine needle aspiration cytology.

Spermatic granulomas may present as tumorlike lesions adjacent to the testis or seminal vesicle and are often associated with infection, trauma or previous surgery. The fine needle aspiration biopsy cytologic findings in three cases of spermatic granuloma are reported. The predominant cytologic features were granulomatous inflammation (nontuberculous and non-foreign body) and spermatozoids (intrahistiocytic or as extracellular spermatic debris). Additional features included lymphoid cells and lymphocytic debris (nuclear tangles), rare plasma cells and eosinophils. Germ cells and acellular (caseous) necrosis were not identified. Well-preserved sheets of epididymal epithelium were occasionally noted. The clinical and cytologic differential diagnoses in such cases are discussed.

Adult↗
PubMedDate not supplied

Paratesticular adenomatoid tumors. The cytologic presentation in fine needle aspiration biopsies.

Adenomatoid tumors are the most common tumors of male paratesticular tissues (epididymis, tunica or spermatic cord) and have also been described in females (uterus, fallopian tube, ovary and paraovarian tissues); fine needle aspiration (FNA) of masses in these locations is increasingly utilized as an alternative to surgical exploration in order to establish a tissue diagnosis. This paper describes the FNA cytodiagnosis of seven cases of paratesticular adenomatoid tumors. The main cytologic criteria included epithelioid sheets and multilayered clusters of monotonous cells with round or ovoid, eccentric nuclei containing small, central nucleoli. Paranuclear clearing with a pink coloration (Giemsa stain) or a clear vacuolelike area (Papanicolaou stain) and abundant cellularity with a background of naked nuclei and stromal fragments were noted. The clinical presentation and clinicohistologic follow-up of these seven cases is also described in detail. A discussion of the differential diagnosis and the expected FNA findings is provided.

Adult↗
PubMedDate not supplied

Patterns of reactivity of four novel monoclonal antibodies (B72.3, DF3, B1.1 and B6.2) with cells in human malignant and benign effusions.

The patterns of immunocytochemical reactivity produced in malignant and benign cells in effusions by staining with the monoclonal antibodies B72.3, DF3, B1.1 and B6.2 are reported. Using the mouse hybridoma methodology, these antibodies were raised against immunogens prepared from membrane-enriched extracts of metastatic carcinoma of the breast. Serial sections from the cell blocks of 20 benign effusions and 59 malignant effusions were incubated with the monoclonal antibodies using the avidin-biotin immunoperoxidase technique. The malignant neoplasms studied included specimens of 18 breast carcinomas, 12 ovarian carcinomas, 14 lung carcinomas, 7 leukemias/lymphomas and 8 miscellaneous malignant neoplasms. The monoclonal antibody B72.3 showed a positive staining reactivity with 36 of 39 adenocarcinomas (92%) versus staining in only 1 of 12 other neoplasms (8%). In contrast to the staining of adenocarcinomas, B72.3 stained no mesothelial cells in a total of 68 specimens tested. The monoclonal antibody DF3 showed a reaction pattern to neoplasms similar to that of B72.3 but also stained mesothelial cells in all of the specimens. The monoclonal antibodies B1.1 and B6.2 exhibited staining characteristics that have been associated with antibodies to carcinoembryonic antigen. The results of this study indicate that the monoclonal antibody B72.3 may function as a highly selective marker in recognizing a cancer cell versus a mesothelial cell and an adenocarcinoma cell versus other malignant tumor cells.

Adenocarcinoma↗