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A Bigotti

Publications and source records attributed to A Bigotti.

At least 37 records · Page 2Linked to original sources
PubMed1992

Regulated expression of vascular cell adhesion molecule-1 in human malignant melanoma.

Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14 (derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and the lines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor--stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas.

Base Sequence↗
PubMed1991

The use of a panel of monoclonal antibodies can lower false-negative diagnoses of peritoneal washings in ovarian tumors.

A correct surgical staging of ovarian carcinoma and the identification of persistent microscopic disease at second-look surgery largely rely on the cytologic examination of peritoneal washings (PW). Nevertheless, the morphologic analysis of these fluids frequently provides false-negative findings. As shown in other areas of cytodiagnosis, monoclonal antibodies (MoAb) to tumor-associated antigens may be a useful adjunct to overcome the limitations of conventional cytopathologic examination of PW. To evaluate this question, immunocytochemical tests were done using a panel of four MoAb to ovarian carcinoma-associated antigens (B72.3, MOv18, MOv19, and OC-125) to analyze 117 PW sampled during initial surgical staging and 121 PW harvested at second-look operations. The results of this study showed that immunocytochemical tests using the combination of the four reagents could improve cytodiagnosis more than 15% in both groups of PW. Thus a significant fraction of patients could be correctly staged and treated or become potentially curable by second-line salvage therapy.

Adenocarcinoma↗
PubMed1991

Tumor progression in human malignant melanoma is associated with changes in alpha 6/beta 1 laminin receptor.

Cells of the melanocytic lineage have been shown to be capable of producing laminin and to lose this property during transformation. In the present study, we have evaluated immunohistochemically whether these changes are paralleled by an altered expression of the alpha 6/beta 1 laminin receptor. Results of this analysis have shown that while nevic cells display high levels of the receptor, this heterodimer undergoes a progressive decrease in expression in cutaneous melanomas of increasing invasiveness. A loss or unco-ordinated expression of the alpha 1/beta complex is present in the majority of the metastatic foci at different body sites. The present results show that during transformation the alpha 6/beta 1 laminin receptor undergoes quantitative alterations and deregulated expression of the 2 subunits. Although the functional relevance of these changes remains unknown, their occurrence in association with modifications of other cellular and extracellular macromolecules associated with tumor progression, strongly suggests a role in human melanoma progression.

Humans↗
PubMed1991

Expression of CAR-3 and TAG-72 macromolecules in normal and transformed endometrium: potential diagnostic application in postmenopausal patients.

Mass cytoscreening for the early diagnosis of endometrial carcinoma has thus far been hampered by the low diagnostic accuracy of current cytopathology. In this study we have analyzed the reactivity of the two monoclonal antibodies, AR-3 and B72.3, recognizing two distinct glycosylated high molecular weight carcinoma associated antigens on histological specimens from normal, hyperplastic, and transformed endometrium with the aim of establishing their diagnostic potential. Because women with a high risk of endometrial cancer are frequently postmenopausal, where normal endometrium is characterized by atrophy and cystic glandular hyperplasia, the following findings were of interest. Both antibodies reacted with variable and apical staining patterns with a minority of specimens of normal cycling endometrium from premenopausal women. However, they were constantly negative when tested on normal atrophic postmenopausal endometrium, and only monoclonal antibody AR-3 occasionally stained glandular cystic hyperplasia. By contrast, lesions with atypical hyperplasia, which represent a preneoplastic condition, were stained by both antibodies in 89 or 67% of the cases depending on the monoclonal antibody used (100% if used in combination). Furthermore, 98% of the endometrial carcinomas tested were found to react with the combination of two monoclonal antibodies. If these findings are confirmed in a multicentric study, the use of the two reagents could be a valuable adjunct in the cytodiagnosis of endometrial cancer, especially in providing a guideline to selecting patients for endometrial curettage and additional diagnostic procedures.

Antibodies, Monoclonal↗
PubMed1991

Comparative analysis of the expression of the extracellular matrix protein tenascin in normal human fetal, adult and tumor tissues.

Tenascin (TN) is a high-molecular-mass oligomeric glycoprotein of the extracellular matrix (ECM) endowed with a programmed expression in embryonic life and a neo-expression in the interstitium of some malignancies. Using monoclonal antibodies (MAbs) which identify human tenascin, we have conducted an extensive immunohistochemical analysis of TN expression in normal fetal and adult human tissues as well as in a wide variety of human tumors. Results of this study demonstrate that TN (1) is detectable in embryonic and fetal tissues at least from the 10th week of gestation; (2) is present in the interstitium of a variety of adult tissues of different embryonic origin; (3) may be neo-expressed in the stroma of benign and malignant tumors; (4) has the ability to accumulate in a highly variable manner in the ECM of tumors of the same and of different histotypes.

Adult↗
PubMed1990

Expression and production of tenascin in benign and malignant lesions of melanocyte lineage.

The distribution of the extracellular matrix (ECM) glyco-protein tenascin (TN) has been evaluated immunohistochemically in benign and malignant lesions of the melanocytic lineage. Results of our study show that TN is detectable in a variety of benign and malignant lesions. In primary melanomas, TN displays a heterogeneous distribution, and a higher degree of expression of this glycoprotein is seen in lesions of greater dermal invasiveness. TN expression does not correlate with that of other ECM glycoproteins such as fibronectin. In vivo and in vitro experiments have also demonstrated that melanoma cells are capable of producing and releasing TN in the extracellular milieu.

Antibodies, Monoclonal↗
PubMed1990

Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues.

The human homolog of the rat neu oncogene, HER2 (also termed c-erbB2) has been demonstrated in amplified form in human breast tumors with poor prognosis. Although amplification of the gene correlates with expression of a 185-kDa transmembrane glycoprotein, no extensive information is available regarding the extent of tissue and tumor specificity of this gene product. We have addressed this issue by immunohistochemically evaluating the expression of p185 HER2 in normal tissue and various tumors using monoclonal antibodies (MAbs) to distinct epitopes of its extracellular domain. No detectable levels of p185 HER2 were found in fetal tissues analyzed, with the exception of renal tubules in 2 out of 3 specimens tested and in intestinal epithelium. In adult tissues, detectable levels of this glycoprotein were found in a restricted number of cell types, the expression being heterogeneous among individuals and cell histotypes. Among the neoplasms assayed p185 HER2 was expressed in 46% of primary breast cancers, in 28% of ovarian tumors and in 30% of colon rectum malignancies. No male breast adenocarcinomas were p185-positive. A large number of other tumors tested revealed only a low incidence of expression of the p185. In metastatic breast tumors p185 HER2 was demonstrated homogeneously among multiple autologous lesions and almost invariably (80%) the expression of p185 in the primary lesion correlated with that of the deriving metastases. Our findings indicate that the expression of the p185 HER2 represents a tumor marker of clinical relevance in breast cancer. Whether this holds true for other malignancies remains to be explored.

Antibodies, Monoclonal↗
PubMed1990

Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesions.

Immunochemical studies have shown that the monoclonal antibody (MoAb) CL203.4, elicited with immune interferon treated cultured human melanoma cells Colo 38, recognizes intercellular adhesion molecule 1 (ICAM-1). The determinant defined by MoAb CL203.4 is distinct and spatially distant from that defined by anti-ICAM-1 MoAb RR1/1, which had been elicited with Epstein-Barr virus-transformed B-lymphocytes from a lymphocyte function associated antigen 1 deficient patient. Immunohistochemical testing with MoAb CL203.4 of surgically removed lesions of melanocyte origin has shown a markedly lower reactivity with benign than with malignant lesions. Among the latter, a higher percentage of metastatic than of primary lesions was stained by MoAb CL203.4. The higher expression of ICAM-1 in metastases than in primary lesions is unique to melanoma, since no difference was found in its distribution in primary and metastatic lesions of a variety of malignancies of different embryological origin. Reactivity with MoAb CL203.4 of primary lesions removed from patients with stage I melanoma showed a highly significant correlation with the lesion thickness and with the clinical course of the disease. The disease free interval in patients without detectable reactivity of their primary lesion with MoAb CL203.4 was significantly (P = 0.004) longer than that of patients whose primary lesion was stained with MoAb CL203.4. These results suggest that ICAM-1 may be a useful marker in the analysis of the molecular mechanism underlying the association between lesion thickness and clinical course of the disease.

Adolescent↗
PubMed1990

Use of MoAb D612 in combination with a panel of MoAb for the immunocytochemical identification of metastases from colon-rectum carcinoma.

During the course of colon-rectum tumours a number of clinical events may occur in which conventional cytopathology can provide only a partial contribution to the definition of a differential diagnosis, i.e. effusions, distant recurrences and second neoplasias. In the present study we have evaluated whether monoclonal antibody (MoAb) D612, recognising a colon-rectum associated antigen, can be used in this context. To this end, MoAb D612 was employed in combination with a panel of MoAb of well defined tumour specificity in immunocytochemical tests. The immunocytochemical findings obtained were compared with the histological and clinical diagnosis. Of 62 effusions and 40 fine needle aspirates studied, MoAb D612 reactivity correlated with the correct diagnosis in 92.8% of the instances. These results indicate that this reagent may help to improve the current cytopathological diagnosis of colon-rectum tumours by identifying the colonic origin of metastases in patients with unknown primary tumour, differentiating ovarian carcinoma from colon metastases to the ovaries and establishing the presence of a second neoplasia in patients with a previous history other than colon carcinoma.

Adenocarcinoma↗
PubMed1989

A monoclonal antibody (D612) with selective reactivity for malignant and normal gastro-intestinal epithelium.

We describe the generation and characterization of a monoclonal antibody (MAb), designated D612, with selective reactivity for malignant and normal gastro-intestinal epithelium. MAb D612, a murine IgG2a, was generated using a membrane-enriched fraction of a human colon carcinoma biopsy as immunogen. Employing radioimmunoassays (RIAs) of biopsy extracts to a range of normal and neoplastic tissues, and both immunofluorescence and immunoperoxidase assays on frozen sections of a range of normal and neoplastic tissues, we have shown that MAb D612 binds to 82% of colorectal carcinomas tested (n = 67) and to normal gastro-intestinal epithelium, but does not bind similarly to either neoplastic or normal tissues from a wide range of other sites. Western blotting has shown MAb D612 to react with a high-molecular-weight antigen. Live cell RIAs and FACS analyses demonstrate the reactive epitope to be present on the surface of colon carcinoma cells. Immunohistochemical studies have shown intense membrane staining of colon adenocarcinomas with MAb D612; the vast majority of both primary and metastatic colon adenocarcinomas from a variety of sites were positive with many lesions showing homogeneous staining of virtually all cells present. Using human effector cells, we also showed that MAb D612 mediates antibody-dependent cell-mediated cytotoxicity (ADCC) of human colon carcinoma cells; this activity was enhanced in the presence of interleukin (IL-2). Radiolabelled D612-purified IgG selectively binds a human colon carcinoma xenograft in situ. The pattern of membrane-associated staining, the molecular weight of the reactive antigen, the IgG2a isotype, the ability to mediate ADCC in the presence of IL-2, and the immunohistochemical and RIA studies demonstrating highly restricted reactivity to malignant and normal gastro-intestinal tissue, all distinguish MAb D612 from other MAbs thus far described.

Adenocarcinoma↗
PubMed1989

Analysis of the antigenic profile of uveal melanoma lesions with anti-cutaneous melanoma-associated antigen and anti-HLA monoclonal antibodies.

The reactivity of 12 surgically removed uveal melanoma lesions with monoclonal antibodies (MoAb) to 14 membrane-bound and 2 cytoplasmic cutaneous melanoma-associated antigens (MAA), to the 2 subunits of HLA Class I antigens and to the gene products of the HLA-D region was compared with that of cutaneous melanoma lesions and correlated with their histiotype. The membrane-bound determinants defined by the anti-Mr 92,000 and 45,000 MAA MoAb TP39.1, anti-Mr 110,000 MAA MoAb M111, anti-Mr 118,000 MAA MoAb TP36.1, anti-Mr 115,000 MAA MoAb 345.134, anti-ICAM-1 MoAb CL203.4 and anti-Mr 31,000 MAA MoAb M2590, and the cytoplasmic determinants defined by the anti-MAA MoAb 465.12 and 2G-10 display a distribution in uveal melanoma lesions similar to that in cutaneous melanoma lesions. On the other hand, membrane-bound determinants defined by the anti-Mr 100,000 MAA MoAb 376.96, anti-9-O-acetyl-GD3 ganglioside MoAb ME311 and anti-GD2-GD3 ganglioside MoAb ME361 were not detected in the uveal melanoma lesions tested. Furthermore, the membrane-bound determinants defined by the anti-GD3 MoAb R24, anti-nerve growth factor receptor MoAb ME20.4, anti-Mr 97,000 MAA MoAb 140.240, anti-carcinoembryonic antigen MoAb B1.1 and anti-HMW-MAA 149.53, 225.28, and 763.74 have a markedly lower expression in uveal than in cutaneous melanoma lesions. Incubation of uveal melanoma lesions with the pool of the MoAb 149.53, 225.28, and 763.74 recognizing distinct and spatially distant determinants of the HMW-MAA increased the intensity of staining of six lesions and stained four lesions which were not stained by the individual monoclonal antibodies. The distribution of HLA Class I antigens in uveal melanoma lesions resembles that in cutaneous melanoma lesions, since they are expressed in all the lesions of the mixed and epithelioid type but were not detected in those of the spindle type, i.e., the counterparts of nevocellular nevi. HLA Class II antigens are expressed with a lower frequency in uveal than in cutaneous melanoma lesions, since they were detected only in 2 of the 12 lesions. One of them is of the mixed type and the other one of the epithelioid type. Besides HLA antigens the determinants defined by the anti-carcinoembryonic MoAb B1.1, anti-ICAM-1 MoAb CL203.4, and anti-GD3 MoAb R24 displayed a differential distribution in the different histiotypes of uveal melanoma, since they are preferentially expressed in lesions of the mixed and epithelioid type.

Animals↗
PubMed1989

Selective changes in expression of HLA class I polymorphic determinants in human solid tumors.

Analysis of surgical biopsies with monoclonal antibodies (mAbs) to framework determinants of major histocompatibility complex class I antigens has shown that malignant transformation is frequently associated with a marked loss of these cell surface molecules. The present study sought to determine whether more selective losses of major histocompatibility complex class I expression occur. Multiple specimens from 13 different types of primary and metastatic tumors were tested utilizing mAb BB7.2, which recognizes a polymorphic HLA-A2 epitope. In each case, expression of HLA-A,B,C molecules was determined by testing with mAb W6/32 directed to a framework HLA class I determinant. We have found that in HLA-A2-positive patients (identified by reactivity of their normal tissues with mAb BB7.2), HLA-A2 products are not detectable or are reduced in their expression in 70-80% of endometrial, colorectal, mammary, and renal tumors; in 40-60% of soft-tissue, skin, ovary, urinary bladder, prostate, and stomach tumors; and in 25-30% of melanomas and lung carcinomas tested. All tumors expressed the framework HLA-A,B,C determinant. The HLA-A2 epitope recognized by mAb BB7.2 is located in a portion of the HLA-A2 molecule postulated to react with the T-cell receptor. Immune surveillance to tumors is thought to depend on cytotoxic T cells, which require corecognition of polymorphic HLA class I epitopes, and on natural killer cells, which are, on the contrary, activated by the absence of HLA class I antigens. The selective loss of an HLA class I polymorphic epitope shown in this study may explain the mechanism by which tumor cells escape both T-cell recognition and natural killer cell surveillance.

Antibodies, Monoclonal↗
PubMed1989

A tumor-associated fibronectin isoform generated by alternative splicing of messenger RNA precursors.

Fibronectin (FN) represents the mixture of a number of structurally different molecules (isoforms) whose make-up varies depending on the FN sources. FN from cultured transformed human cells has a very different isoform composition with respect to its normal counterpart. In fact, SV-40-transformed WI-38VAI3 human fibroblasts produce high levels of a FN isoform (B-FN) which is very poorly expressed in their normal, WI-38, counterpart. We have recently demonstrated that the B-FN isoform derives from a differential splicing pattern of the FN primary transcript which leads, in transformed cells, to a high level expression of the exon ED-B (Zardi, L., B. Carnemolla, A. Siri, T. E. Petersen, G. Paolella, G. Sebastio, and F. E. Baralle. 1987. EMBO (Eur. Mol. Biol. Organ.) J. 6:2337-2342). Here we report on the production and characterization of a monoclonal antibody (BC-1) which recognizes an epitope within the protein sequence coded for by the ED-B exon. This monoclonal antibody makes it possible to carry out immunohistochemical analysis of the distribution of the ED-B-containing FN isoform (B-FN) in human tissues. The results show that while in normal, adult, human tissues total FN has a widespread distribution, the B-FN isoform is restricted only to synovial cells, to some vessels and areas of the interstitium of the ovary, and to the myometrium. On the contrary, the B-FN isoform has a much greater expression in fetal and tumor tissues. These results demonstrate that, in vivo, different FN isoforms have a differential distribution and indicate that the B-FN isoform may play a role in ontogenesis and oncogenetic processes.

Antibodies, Monoclonal↗
PubMed1987

Immunohistochemical detection of antigen in human primary and metastatic melanomas by the monoclonal antibody 140.240 and its possible prognostic significance.

An indirect immunofluorescence technique was used to study the tissue distribution of the epitope recognized by the monoclonal antibody 140.240 which identifies a p97-like melanoma-associated oncofetal antigen. Cryostat sections of various normal and neoplastic human tissues were examined. The presence of antigenic activity was demonstrated in 20 of 39 (51%) primary skin melanomas, in 21 of 52 (40%) metastatic melanomas, and in 20 of 44 (45%) nevi. The reactive nevi were restricted to intradermal, junctional, compound and spindle cell types. Of the 110 samples of 12 major tumor types other than melanoma tested, only 1 of 6 epidermoid tumors, 1 of 4 benign breast tumors and 1 of 5 prostatic tumors gave weak staining. This antibody also reacted with sweat glands and fetal small intestine tissue, but not with other adult or fetal normal tissues. Intrapatient as well as interpatient heterogeneity in the epitope expression was present in primary as well as metastatic tumor lesions surgically removed from patients with melanoma. Evaluation of the immunohistologic data and the clinical outcome of patients with melanoma reveals that the expression of the epitope recognized by this antibody is associated with a more favorable prognosis.

Antibodies, Monoclonal↗
PubMed1986

Gene products of the HLA-D region in normal and malignant tissues of nonlymphoid origin.

Indirect immunofluorescence staining with monoclonal antibodies has shown a differential distribution of HLA-DR, DQ, and DP antigens in normal tissues of nonlymphoid origin. The distribution of HLA-DP antigens is similar to that of HLA-DR antigens, while that of HLA-DQ antigens is more restricted. Malignant transformation of cells of nonlymphoid origin may be associated with the appearance of the gene products of the HLA-D region. HLA-DR antigens appear more frequently than the other two types of HLA class II antigens and HLA-DP antigens more frequently than HLA-DQ antigens. Differential expression of the gene products of the HLA-D region was also found in autologous metastases removed from different anatomic sites from patients with melanoma. The HLA class II phenotype of surgically removed malignant lesions did not correlate with the degree of differentiation of tumor cells and/or with the expression and/or cellular distribution of HLA class I antigens. Furthermore, in melanoma lesions, no relationship was found between the HLA class II phenotype and the expression of 3 membrane bound and 1 cytoplasmic melanoma associated antigen recognized by monoclonal antibodies. The functional significance and the practical implications of the differential expression of the gene products of the HLA-D region by tumor cells are discussed.

Antibodies, Monoclonal↗