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Biomedical subjects

B Caillou

Publications and source records attributed to B Caillou.

At least 91 records · Page 5Linked to original sources

[In vivo imaging of Hodgkin's lymphomas using monoclonal antibodies].

The Hodgkin- and Reed-Sternberg cell associated monoclonal antibody HRS-1 was labeled with radioactive iodine and injected into 6 patients with Hodgkin's lymphoma for immunoscintigraphic imaging. Four of five patients who received 131I-labeled HRS-1 had a positive immunoscintigram. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Bony disease was demonstrated by immunoscintigraphy in this patient. These preliminary results demonstrate that immunoscintigraphy with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value of immunoscintigraphy in Hodgkin's lymphoma must be determined in a larger series of patients. Several modifications of the technique such as the use of Fab or F(ab')2 fragments should further improve the results.

Adolescent↗

Comparison of sporadic and hereditary forms of medullary thyroid carcinoma.

Between 1960 and 1988, 185 patients with medullary thyroid carcinoma (MTC) were followed at the Institut Gustave Roussy in France. The screening of the family members by calcitonin measurement (basal or after pentagastrin stimulation) has led to the characterization of 38 sporadic cases and 44 hereditary cases. Among the hereditary cases are seven families with MTC only and two families with multiple endocrine neoplasia type 2A (MEN 2A). MTC only cases and MEN 2B cases are present as apparently sporadic forms. Hereditary cases consisted of 26 females and 18 males; the male:female ratio was 21:17 in sporadic cases. Ten of the sporadic patients were deceased (mean age 46 years) compared to three of the hereditary cases (mean age 59 years). The age at diagnosis was 44 years for the sporadic patients and 35 years for the hereditary MTC only patients with clinical manifestations. Histologic data from the sporadic and hereditary patients showed that the tumor is mostly unilateral without C-cell hyperplasia in sporadic cases and bilateral with C-cell hyperplasia in hereditary cases. The location of tumors was quite variable among the sporadic cases and mostly localized to the middle part of the thyroid lobes in the hereditary cases. Our data suggest that the age at diagnosis is later in sporadic forms of MTC and that the age at diagnosis is later in the hereditary forms of MTC only compared to those with MEN 2A.

Adult↗

Establishment and characterization of three transplantable EBV-containing nasopharyngeal carcinomas.

Three transplantable nasopharyngeal carcinoma (NPC) tumors, designated C15, C17 and C18, have been obtained and characterized. C15, derived from a primary NPC tumor, has been propagated in nude mice for 30 passages. C17 and C18, derived from metastatic NPC tissue, have been passaged 10 times. Desmosomes, present in every case, provided confirmation of the epithelial origin of all 3 tumors. The Epstein-Barr virus (EBV) genome is contained in C15, C18 and C17 tumor cells with 30, 12 and 3 copies, respectively. The Epstein-Barr virus nuclear antigen (EBNA) was stained by the classical anti-complement immunofluorescence (ACIF) technique. Fluorescence intensity was strong in C15, moderate in C18, and hardly detectable in C17 cells. No expression of the EA and VCA antigens was detected. Flow cytometry analysis performed on monocellular suspensions showed the absence of detectable CR2 molecules (the EBV receptor on B lymphocytes) in all 3 tumors, and the constitutive expression of HLA class-II antigens in C15 and C17 cells. IL-1 activity was demonstrated in the supernatant of C15 and C17 cells cultivated in vitro for 3 days. These data confirm that the constitutive synthesis of MHC class-II molecules and the release of IL-1-like activities are frequent features of NPC cells. These characteristics could be of importance in relation with the T-cell infiltrate found in NPC primary tumors.

Adolescent↗

Construction and clinical validation of a sensitive and specific assay for serum mature calcitonin using monoclonal anti-peptide antibodies.

Using calcitonin (CT) as an hapten, we have generated a library of monoclonal antibodies. Six monoclonal antibodies were developed and analyzed with respect to affinity and specificity for epitopes on CT by enzyme linked immunosorbent assay and radioimmunoassay. These antibodies were used in the construction and the optimization of a two-site monoclonal immunoradiometric assay (m-IRMA) for CT. We used a combination of two monoclonal antibodies to develop an assay which is rapid (overnight incubation), sensitive (10 pg/ml) and strictly specific for the mature form of calcitonin, ie the 32 amino acid-long polypeptide bearing a prolineamide as the C-terminal residue. This assay was utilized to demonstrate that mature calcitonin circulates as heterogeneous molecular species resulting from polymerization of calcitonin by disulphide linkage and/or by aggregation on irrelevant proteins. The clinical relevance of this assay was studied on a series of patients with medullary carcinoma of the thyroid (MCT) and the characteristics of the assay was compared with those of a conventional polyclonal radioimmunoassay. The m-IRMA for CT proved to be useful for both the diagnosis and the follow-up of MCT.

Adult↗

Acetylcholinesterase and butyrylcholinesterase activities in human thyroid cancer cells.

The appearance and distribution of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in 12 human thyroid cancers and three normal thyroids were examined by electron microscopic study with indirect thiocholine method. The demonstration of AChE and BuChE activities in only two of nine cases of follicular and papillary carcinoma examined and none of the three cases of medullary carcinoma shows that the cholinesterases are not specific enzymes for the thyroid tumors. In normal thyroid tissue samples examined, no activities of AChE and BuChE were detected. On ultrastructural level AChE reaction product was revealed in the perinuclear space, in the endoplasmic reticulum, and in the Golgi complex of some but not in all cells in less-differentiated regions of the tumors. In contrast to the distribution of AChE, no staining for BuChE was noted in the Golgi elements. Ultrastructural localization of AChE activity in the thyroid cancer cells corresponds exactly to the current understanding of glycoproteins synthesis and processing in normal cells. The authors postulate that the copy of AChE gene suppressed in normal thyroid epithelium cells may be expressed in some follicular thyroid carcinoma cells. Their hypothesis is logical on the basis of recent finding of a significant homology between AChE and thyroglobulin.

Acetylcholinesterase↗

Lymphoblastic lymphoma in adults: a clinicopathological study of 34 cases treated at the Institut Gustave-Roussy.

We report a series of 34 adult patients with lymphoblastic lymphoma treated at our Institute between 1977 and 1986. At presentation, mediastinal involvement was seen in 76%, extranodal involvement (not including bone marrow) in 20%, stage IV in 53% and circulating blasts in 15%. In the 15 cases where immunological studies were performed, 12 proved to be of T type and the other three lacked both T and B markers. Chemotherapy with acute lymphocytic leukemia (ALL) protocols was given to 58% and lymphoma protocols to the other patients, with CNS prophylaxis given to a total of 28 patients. Although complete remission (CR) was observed overall in 74% of patients, 5 year survival was only 22% (42% in stages I-II and 8% stages III-IV) with improved results seen with recent aggressive anti-leukemic protocols. Five relapsed patients entered second CR and two were still in CR at this time. CNS relapse occurred in a total of eight patients (three without prophylaxis), and was isolated in two of six patients who achieved CR (despite CNS prophylaxis). In an analysis of prognostic factors, only the attainment of a CR was statistically significant (P less than 0.001). Thus we are unable to confirm other studies which demonstrated prognostic variations in this disease and believe that all such patients should receive aggressive chemotherapy with substantial CNS prophylaxis similar to those currently used for ALL.

Adolescent↗

Structure and expression of c-myc and c-fos proto-oncogenes in thyroid carcinomas.

Tumour specimens from 23 patients with thyroid carcinoma, 22 patients with thyroid adenoma, 3 with Graves' disease, and tissues from 8 normal thyroid glands were analyzed by Southern blot hybridization for the physical state of c-myc and c-fos proto-oncogenes. In 4 patients, both the primary tumour and lymph node metastases were analyzed. No amplification or rearrangement of the two proto-oncogenes was detected. Total RNAs were also analyzed. Elevated levels of the 2.4 kb c-myc RNA and of the 2.2 kb c-fos RNA were found in 13/23 (57%) and 14/23 (61%) of the cancer patients, respectively. High levels of c-myc transcripts were more frequently found in thyroid carcinomas with unfavourable prognosis. Concomitant elevated levels of both c-myc and c-fos RNAs were found in 8 cancers. High levels of c-myc RNA were also found in 1 out of 22 specimens of adenoma, in 1 specimen of Graves' disease and in 2 normal thyroid glands. High levels of c-fos RNA were found in 20 of the 22 adenoma samples and in 2 out of 8 normal thyroid tissues. These data indicate that the overexpression of c-myc and c-fos genes is independent of an alteration of the loci. The high levels of c-fos found in adenoma may be associated with the differentiation state of these tumours.

Adenoma↗

Morphological and functional differentiation of human thyroid cells in collagen gel culture.

In order to study the expression of the morphological and functional characteristics of human thyroid cells, 3-dimensional cultures were carried out in collagen gel. This substrate allows the cells to retain their organization in follicles with a normal polarity. Cellular polarities appeared normal at the time of collagen embedding, but there was a delay of 4-5 days in culture before the maximal TSH stimulation of 125I- uptake and of cAMP accumulation occurred. In normal and adenoma-derived cells, 125I- uptake, which could be increased by TSH, was demonstrated. cAMP accumulated in the culture medium and thyroglobulin was secreted into the follicle lumen. Of the 4 differentiated carcinomas for which the 72-hr uptake of 125I- was measured, only 2 displayed slight 125I- uptake and response to TSH. Thus, human thyroid cells exhibit better morphological and functional differentiation in collagen gel culture than in monolayer culture. Furthermore, in a variety of pathological cases studied, the expression of specific characteristics in culture varied in a fashion similar to differences observed in vivo.

Adenoma↗

[Medullary cancer of the thyroid: morphological and immunohistochemical definitions. The pathologist's role in 1987].

The morphological and secretories aspects of medullary thyroid carcinomas are reviewed. Mixed follicular and medullary carcinomas are discussed. Criteria for discrimination between sporadic and hereditary forms are mentioned with special reference on C cell hyperplasia. After a brief report on what is known about normal human and animal C cell, a short histogenetic discussion is debated.

Calcitonin↗

Detection of activated ras oncogenes in human thyroid carcinomas.

Focus formation following DNA transfection of mouse 3T3-Vill cells was used to search for the presence of activated oncogenes in human thyroid tumors. Oncogenes belonging to the ras family were detected in four out of six thyroid carcinomas (Ki-ras in one anaplastic tumor and one follicular moderately differentiated tumor and Ha-ras and N-ras in two papillary tumors). Normal thyroid tissue samples obtained from two patients, one with an anaplastic tumor and one with a benign adenoma, and samples from 4 benign adenomas and from one toxic goiter of a patient with Graves' disease gave negative results. In one case, restriction enzyme analysis demonstrated the presence of a mutation in codon 12 of the activated Ha-ras oncogene. Our data show that all three ras proto-oncogenes can become activated in malignant thyroid tumors.

Adenoma↗

Identification of a subset of normal B cells with a Burkitt's lymphoma (BL)-like phenotype.

Fresh biopsy cells from cases of Burkitt's lymphoma (BL) display a homogeneous cell surface phenotype. The cells were found to be reactive with the pan B cell marker B1, and consistently co-expressed the BL-associated glycolipid antigen, BLA, and the common acute lymphoblastic leukemia antigen, CALLA, but lacked the B cell "activation" antigens characteristically expressed on EB virus-transformed normal B cells. Microscopic and cell sorter analysis of cells isolated from a series of fresh normal tonsils have identified a subpopulation of normal B cells carrying the same cell surface markers. That BLA and CALLA could be co-expressed on individual B cells was demonstrated by two-color immunofluorescence (IF) of tonsils in suspension, and immunoperoxidase (IP) staining of serial tonsil sections. These BLA+, CALLA+, "activation" antigen- cells were further characterized as B1+, sIgM+, sIgD-, C3d/EB virus receptor+ and were susceptible to virus-induced transformation in vitro. IF studies on Percoll-fractionated tonsillar cell populations and direct examination of IP-stained tonsil semi-thin sections indicated that the BLA+, CALLA+ cells were localized in germinal centers. Their morphological characteristics matched those of BL cells, and their location within germinal centers was consistent both with the known phenotype of germinal center tonsillar B cells and with the description of BL as a proliferation of centroblasts. We suggest that this population of tonsillar germinal center B cells provides the normal counterpart of BL tumor cells.

Antibodies, Monoclonal↗

A 93-kDa glycoprotein expressed on human cultured monocytes and dendritic reticulum cells defined by an anti-K562 monoclonal antibody.

An IgG2a monoclonal antibody, referred to as 12B1 and raised against the K562 cell line, reacted with adherent monocytes maintained in culture for several days but not with bone marrow or peripheral blood cells including freshly isolated monocytes. Among human leukemic cell lines, 12B1 reacted essentially with the promyelocytic HL60 cell line. 12-O-Tetradecanoylphorbol 13-acetate treatment, but no other differentiation inducer, strongly enhanced its reactivity on K562, HL60 and the histiocytic U937 cell line. Immunoperoxidase staining of sections of normal human tissues showed that 12B1 specifically recognized dendritic reticulum cells in germinal centers of lymph nodes, spleen and tonsils. The 12B1-detected antigen is a highly glycosylated polypeptide of an apparent molecular mass of 93-86 kDa. The 12B1 antigen appears to be a new glycoprotein marker shared by adherent monocytes and dendritic reticulum cells. The association of the 12B1 epitope with cells which present antigen and/or exert accessory function suggests that this molecule could play a role in these activities.

Antibodies, Monoclonal↗

Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma.

We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.

Adult↗