Improvement of cytodiagnosis of ovarian tumors employing monoclonal antibodies.
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Antibodies, Monoclonal↗
Biomedical subjects
I Venturo
Publications and source records attributed to I Venturo.
Integrin (alpha 6/beta 4) expression in human lung cancer as monitored by specific monoclonal antibodies.
In this study, the expression of the alpha 6/beta 4 integrin complex was analyzed in human lung carcinomas both in vitro and in vivo, using two monoclonal antibodies which recognize the integrin subunits alpha 6 (Mab 135-13C) and beta 4 (Mab 439-9B). Immunoprecipitation patterns obtained from established human lung carcinoma cell lines demonstrated that the alpha 6 and the beta 4 subunits were differentially expressed in carcinomas of different types. The alpha 6 subunit was expressed in all the cell lines tested (squamous cell carcinoma A431, adenocarcinoma A549, large cell carcinoma DG3, and small cell carcinoma AE2). The beta 4 subunit was expressed in non-small cell cancer lines but was not detectable in the small cell cancer line tested. Using a quantitative two-site assay, we measured the concentration of the alpha 6/beta 4 integrin in matched biopsies from primary lung tumors and from normal lung. These studies confirmed that the complex was differentially expressed in non-small versus small cell lung cancers and that it was also detectable in lysates from normal lung at low levels. The highest levels of alpha 6/beta 4 were found in moderately differentiated squamous cell carcinomas. By immunohistochemistry, the beta 4 subunit was detectable in all the squamous cell carcinoma and adenocarcinomas tested (a total of 59), but not in 10 small cell cancers. The patterns of immunoreactivity were consistent with the expected distribution of membrane glycoproteins and, in some squamous cell carcinomas, were suggestive of the localization displayed by molecules involved in carcinoma-stroma interaction. Immunohistochemical staining indicated that beta 4 was also expressed in specific types of nonrespiratory pulmonary epithelial cells.
Adenocarcinoma↗
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↗
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↗
Second generation monoclonal antibodies to the human integrin alpha 6 beta 4.
Second generation monoclonal antibodies to the alpha 6 beta 4 subunits of human integrins have been prepared. MAbs 450-9D, 10D, and 11A1 react at different sites on the beta 4 molecule and MAbs 450-30A1 and 33D react at the same site on the alpha 6 subunit. Double determinant (two-site) radioimmunoassays using combinations of these MAbs have been developed. Two assays for beta 4 distinguish between the whole beta 4 molecule and the beta 4 molecule truncated from the C-terminus (form c) while another assay measures the presence of alpha 6 subunits. Data from the two-site assays support the following conclusions: (1) Colon tumors and normal colon mucosa express large amounts of alpha 6 beta 4 although only form c of the beta 4 was detected; (2) There is no evidence for alpha 6 beta 1 expression in colon; however, some of this complex may be present in certain lung tumors. The extracellular domains of alpha 6 and beta 4 can associate with each other even if the cytoplasmic domain of the beta 4 subunit is not present. MAbs to specific domains of the beta 4 molecule may be useful in analyses of forms a and c in normal and malignant tissue. The fact that only the largest beta 4 molecule "a" retains the phosphorylation site may have functional significance.
Animals↗
Combinations of monoclonal antibodies can distinguish primary lung tumors from metastatic lung tumors sampled by fine needle aspiration biopsy.
Transthoracic fine needle aspiration (FNA) biopsies performed under computed tomography (CT) scan (CT-FNA) have greatly improved the cytodiagnosis of lung tumors. However, the distinction between a primary lesion and a metastatic lesion still may be difficult on the basis of morphologic criteria. To evaluate whether a selected panel of monoclonal antibodies (MoAb) to tumor-associated antigens (TAA) can improve the diagnostic potential of FNA, we have immunocytochemically analyzed 122 pulmonary CT-FNA. Whereas conventional cytology was capable of recognizing only the neoplastic nature of the lesions, the immunocytochemical diagnosis could identify the primary or metastatic nature of the pulmonary masses in 92.5% of the cases. The immunocytochemical findings were confirmed by clinical-histopathologic data. The current results demonstrate that the use of immunocytochemical methods can significantly improve the diagnostic accuracy of conventional cytology of lung masses.
Adult↗
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↗
Treatment of malignant pleural effusions with intracavitary Corynebacterium parvum.
Fifty-three cases of metastatic pleural effusion (30 haemorragic and 23 serofibrinous) were treated with 4 mg of Corynebacterium parvum (CP) injected weekly into the pleural cavity after total thoracentesis. Of the 53 effusions, 24 were metastases from lung cancer and 29 from breast cancer. Complete response (CR) was assessed as total resolution of pleural effusion after explorative thoracentesis. The results were as follows: 15 CR after two injections of CP, 30 CR after three, and 5 CR after the fourth administration. Three of 53 cases could not be evaluated because of early death. Of the 30 clearly haemorragic effusions, 25 turned into serofibrinosis after the first intrapleural injection of CP and the other five after the second. These findings indicate that intracavitary CP is the most adequate treatment for the control of neoplastic pleural effusion because it induces a significant clinical improvement with milder side effects with respect to other drugs and/or physical agents commonly used.
Bacterial Vaccines↗
Use of selected combinations of monoclonal antibodies to tumor associated antigens in the diagnosis of neoplastic effusions of unknown origin.
While conventional cytodiagnosis can, in most instances, recognize cancer cells in metastatic effusions from solid tumors, the cellular type or the organ of origin of the primary neoplasia can rarely be determined only on the basis of their morphology. In the present study we have evaluated whether immunocytochemical techniques can be used to overcome this limitation by employing a panel of monoclonal antibodies (MoAbs) to tumor associated antigens (TAA) which lack detectable reactivity with mesothelial cells. To this end we have analyzed, by indirect immunofluorescence, cytospins of 60 malignant effusions of unknown origin. The results of this study have shown that the definition of the origin of the primary tumor, which was subsequently confirmed histologically and/or clinically, could be reached in 87% of the cases. These findings demonstrate that selected combinations of MoAbs, when used in immunocytochemical tests, can provide a powerful diagnostic tool in defining the site of cryptic primary neoplasias causing metastatic effusions.
Antibodies, Monoclonal↗
[Evaluation of the results of a study of 343 cases of pulmonary carcinoma drawn from a file of related findings].
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Adult↗
Combination therapy with progestins and tamoxifen in advanced breast cancer: A preliminary report.
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Adult↗
[Polychemotherapy with cis-diammino-dichloroplatinum in non-seminoma testicular tumors. Personal experience].
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Adult↗
[IL-6, p53 and proto-oncogene c-myc play different roles as biological markers of plasma cell dyscrasias].
PURPOSE: To determine the role of serum levels of IL-6 and p53 mutant protein as well as of c-myc proto-oncogene alterations: a) in discriminating between benign (MGUS) and malignant Plasma cell dyscrasias (Multiple and Microsecreting Myeloma, Plasmocytoma); b) in monitoring the clinical course of malignant forms of this disease. PATIENTS AND METHODS: Eighty-eight patients affected by Plasma cell dyscrasias (58 MGUS, 24 MM and 6 PLC) entered this study. Using commercially available ELISA kits, serum levels of IL-6 and p53 have been determined in all the patients. In addition, a selected group of patients (n = 30) was also analyzed for structural c-myc gene alterations by Southern blot technique. RESULTS: The results show that, conversely from p53 protein, IL-6 and c-myc gene may represent useful diagnostic markers for discriminating benign from malignant forms of Plasma cell dyscrasia. On the contrary, preliminary findings of the same work indicate a potential role for the mutant p53 protein in monitoring the response to chemotherapy of patients affected by MM or PLM. CONCLUSIONS: Overall, these data suggest that the combined use of IL-6, p53 and c-myc may provide a new approach for a more rational management of Plasma cell dyscrasia patients.
Adult↗
Multiple genetic lesions in solid tumors: relevance to diagnosis, prognosis, and molecular mechanisms.
In recent years, significant progress has been made in identifying characteristic chromosomal and molecular rearrangements associated with several solid tumors. Most solid tumors studied have been found to be characterized by recurrent chromosomal abnormalities that are specific to histologic types. We have studied primary specimens of malignant melanoma, gastrointestinal cancer, renal carcinoma, lung and ovarian cancer, by cytogenetic and molecular means, and we discuss the genetic alterations found. Brief descriptions of the potential clinical utility, and biological relevance changes in these disorders are also discussed.
Aged↗
[Sequential therapy with methotrexate and 5-fluorouracil in patients with advanced colorectal cancer pretreated with 5-fluorouracil plus folinic acid].
PURPOSE: To evaluate the efficacy and toxicity of a sequential low-dose methotrexate (MTX) and 5-fluorouracil (5FU) regimen in the palliative treatment of patients with advanced colorectal cancer. PATIENTS AND METHODS: Enrolled in the study were patients with advanced colorectal cancer, refractory to 5FU + FA. Patients were treated with MTX 40 mg/m2 i.v. bolus d 1 and 8, 5FU 700 mg/m2 i.v. bolus d 2 and 9 (24 hours after MTX bolus). The cycle was repeated every 4 weeks. RESULTS: 48 patients entered the study, and 45 are evaluable. The overall response rate was 15% with 1 complete response and 6 partial responses. Eight patients obtained disease stabilization. Median time to progression was 9 months. Toxicity was mild. Grade 3 stomatitis was observed in 7 (15%) patients. CONCLUSIONS: Sequential MTX/5FU is a well tolerated regimen with mild antitumor activity in refractory advanced colorectal patients.
Antineoplastic Combined Chemotherapy Protocols↗