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B Caillou

Publications and source records attributed to B Caillou.

At least 19 recordsLinked to original sources
PubMed1996

Thyroid pathologies in transgenic mice expressing a human activated Ras gene driven by a thyroglobulin promoter.

Four transgenic mice carrying the human activated c-Ha-Ras gene, the expression of which was driven into the thyroid gland by a bovine thyroglobulin promoter, have been produced. The M1 and M2 mice developed papillary thyroid carcinomas and the M2 mouse also developed a lung carcinoma, however none of them transmitted the transgene. Both the M3 and the M4 mice gave rise to transgenic lines. M3 progeny mice develop a goitre with morphological aspects of hyperplasia as well as a thymus hyperplasia. M4 developed a papillary thyroid carcinoma and a lung carcinoma. Lung tumors but not thyroid tumors were observed in M4 adult transgenic progeny. In this M4 line, thyroid dysgenesis leading to growth retardation and premature death was observed upon serial backcross that enhanced the DBA/2J genetic background. The development of thyroid tumors in M1, M2, M4 transgenic mice demonstrates the oncogenic potential of activated Ras gene in the thyroid gland. The M4 line raises interesting questions relative to the interference between the Ras-mediated signal transduction pathway and thyroid morphogenesis.

Animals↗
PubMed1996

Octreotide scintigraphy in patients with differentiated thyroid carcinoma: contribution for patients with negative radioiodine scan.

Somatostatin receptor scintigraphy (SRS) was evaluated in 25 differentiated thyroid carcinoma (DTC) patients. All DTC patients had elevated thyroglobulin levels. A total body scan (TBS) was performed 4 and 24 h after injection of indium-111-DTPA-Phe-octreotide. Group 1 included 16 patients with negative 131I TBS; group 2 had 9 patients with positive 131I TBS. SRS results were compared to the results of conventional imaging methods in group 1 and to 131I TBS in group 2. 131I TBS was performed after administration of a therapeutic dose of 131I in all patients except one. SRS was positive in 20 of 25 (80%) patients. In group 1, SRS was positive in 12 of 16 patients; in the 3 patients with no previously known tumor site, SRS visualized one abnormal neck focus of uptake in two. In the other 13 patients, SRS disclosed unknown mediastinal foci in 2, but visualized less organ involvements and a smaller number of tumor sites than conventional imaging methods. In group 2, SRS was positive in 8 of 9 patients and visualized an identical (7 patients) or a smaller number (1 patient) of involved organs than 131I TBS; in 2 patients, SRS allowed the discovery of 1 abdominal and 1 bone tumor site. We suggest than SRS should guide imaging modalities in DTC patients with negative 131I TBS and be an alternative to 131I TBS in DTC patients unable to withdraw T4 treatment.

Adult↗
PubMed1995

Activating mutations of the TSH receptor in differentiated thyroid carcinomas.

A series of 14 thyroid carcinomas, characterized for their basal adenyl cyclase activity (ACA), was examined for the presence of activating point mutations in the TSH receptor (TSHR) gene. Sequencing of the carboxyl-part of this gene revealed the presence of a somatic and heterozygotic point mutation in codon 623 in three out of six tumors showing a constitutively enhanced ACA and a poor response to TSH stimulation. The mutation determines the substitution of a serine for an alanine in the third intracellular loop of the receptor, in a region critical for signal transduction. One tumor bearing a TSHR mutation presented also a N-ras point mutation. Both mutations were detected also in a lung metastasis of this tumor. Our data represent the first report of alterations in the TSHR gene in thyroid malign neoplasia. TSHR mutations may indeed participate, as well as the G alpha s protein (gsp oncogene), in the oncogenesis of some differentiated thyroid carcinomas presenting increased basal levels of cAMP and a poor response to TSH.

Adenocarcinoma, Follicular↗
PubMed1995

Pattern of ras and gsp oncogene mutations in radiation-associated human thyroid tumors.

The preferential activation of the Ki-ras oncogene in follicular radiation-associated human thyroid carcinomas, has been suggested by Wright et al. (1991). However, only 12 thyroid tumors were analysed in this study. In order to confirm if radiation favours, in human thyroid tumorigenesis, the appearance of a particular molecular lesion, we studied 33 benign and malignant human radiation-associated thyroid tumors. We used polymerase chain reaction (PCR) amplification and allele-specific hybridization with mutant-specific probes for the three ras genes and the gsp oncogene. Compared to 85 'spontaneous' human thyroid tumors, the radiation-associated cases: (1) show a similar overall frequency of ras and gsp mutations (about 30% and 6% respectively); (2) present a similar frequency of mutation of the three ras genes without any predominance in adenomas and papillary carcinomas and (3) all Ki-ras mutations were found in papillary carcinomas (4/15). ras and gsp genes were never found mutated simultaneously, suggesting an alternative role for both oncogenes in the thyroid tumorigenic radiation-associated process.

Adenoma↗
PubMed1995

Genetic alterations in thyroid hyperfunctioning adenomas.

Thirty-seven thyroid autonomously hyperfunctioning adenomas were screened for mutations in the TSH receptor (TSHR), G alpha s (gsp), and ras genes. Polymerase chain reaction-amplified fragments of the TSHR C-terminal part (exon 10), the G alpha s (exons 8 and 9), and the three ras genes were obtained from the genomic DNA extracted from 37 tumors and their adjacent normal tissues and were studied by direct nucleotide sequencing and hybridization with synthetic probes. A point mutation in the third intracellular loop (codon 623) of the TSHR was found in 3 of 37 adenomas studied. This mutation codes for a change (Ala to Ser) in the TSHR structure and is somatic and heterozygotic. Constitutive activation of the TSHR was demonstrated by an increase in basal cAMP levels after transfection of Chinese hamster ovary cells with a mutated Ser623-TSHR complementary DNA. Nine gsp[00ae]MDRV[00af]- and one ras-activating mutations were also detected. No simultaneous alteration of the studied genes was present. Thus, in hyperfunctioning thyroid adenomas, our data suggest that a mutational activation of the TSHR and gsp genes may play a tumorigenic role through constitutive activation of the cAMP pathway.

Adenoma↗
PubMed1995

Radiolabeled somatostatin analog scintigraphy in differentiated thyroid carcinoma.

UNLABELLED: After intravenous administration of a radiolabeled somatostatin analog (octreotide), an image of the thyroid gland is frequently observed; few data are available, however, on somatostatin receptors in epithelial thyroid cells assessed in vitro and on images of differentiated thyroid carcinoma (DTC) with pentetreotide scintigraphy. METHODS: In four patients with metastatic thyroid carcinoma, whole-body scintigraphy was performed 4 to 48 hr after injection of 110 MBq of 111In-pentetreotide. The results were compared to data obtained with other imaging modalities, including scintigraphy performed after administration of a therapeutic dose of 131I. RESULTS: There were positive foci in distant metastases on 111In-pentetreotide scintigraphy. Pentetreotide scintigraphy was positive in two patients with an "insular" form of DTC, one of whom had a positive (faintly) 131I scan. Of the other two patients with papillary DTC without radioiodine uptake, only one exhibited a certain degree of pentetreotide scintigraphy positivity in distant metastases. CONCLUSION: These results show promise for exploration of insular thyroid carcinoma and suggest that these carcinomas may possess functional differentiation features, including somatostatin receptors.

Bone Neoplasms↗
PubMed1995

Comparison of radiolabeled octreotide and meta-iodobenzylguanidine (MIBG) scintigraphy in malignant pheochromocytoma.

METHODS: The results of in vivo somatostatin scintigraphy were correlated with those of MIBG from 14 patients, aged 22-66 yr, with metastatic pheochromocytoma (10 patients), malignant paraganglioma (3 patients) and metastatic ganglioneuroblastoma (1 patient). Twelve patients had elevated catecholamine excretion. A dynamic study and serial whole-body scans (4-48 hr) were obtained after injection of 130-187 MBq of 111In-DTPA-Phe-1-octreotide. When indicated, SPECT imaging was done. The results were compared to MIBG scans obtained after a diagnostic or a therapeutic dose. RESULTS: Three patients with more than 20 tumor sites on MIBG scans had only 1-9 sites on 111In-octreotide scintigraphy. Two patients had no MIBG uptake but one had lung uptake on octreotide scintigraphy. In the other 9 patients with a total of 41 foci of MIBG uptake, 33 sites of 111In-octreotide uptake are found. All positive images with octreotide scintigraphy were seen at or before 4 hr, but the contrast improved at 24 hr. Uptake intensity was lower with 111In-octreotide than MIBG and the number of tumor sites was higher with MIBG. However, seven foci were positive only on octreotide scintigraphy and six of them could not be confirmed by other imaging modalities. CONCLUSION: Use of octreotide to identify somatostatin receptors seems promising, especially when results from MIBG scans are negative. Moreover octreotide images could aid in determining a treatment regimen as well as establishing the extent of disease and prognosis.

3-Iodobenzylguanidine↗
PubMed1994

Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.

Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (Gs) alpha subunit in the thyroid gland. The expression of the mutant Arg-201-->His Gs alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter. The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [125I]iodine and produced elevated levels of circulating triiodothyronine and thyroxine. These animals demonstrate that the mutant form of Gs alpha subunit carries an oncogenic activity, thus supporting the model that deregulation of cAMP level alters growth control in thyroid epithelium. These animals represent models for humans with autonomously functioning thyroid nodules.

Animals↗
PubMed1994

Identification of genes overexpressed in tumors through preferential expression screening in trophoblasts.

Early trophoblastic cells share several features with neoplastic cells. Based on that observation, we attempted to identify genes overexpressed in tumors by analyzing genes preferentially expressed in trophoblasts. A subtracted library enriched in complementary DNA from early cytotrophoblasts was constructed, and the expression level of selected recombinants was analyzed on a large panel of normal and tumor tissues. The library was prepared using a polymerase chain reaction-based complementary DNA subtraction method with 6-week amenorrhea cytotrophoblast endoplasmic reticulum-bound RNA as target, and a mixture of complementary DNA prepared from terminal placenta and activated T-lymphocytes as driver. Two rounds of screening were performed to isolate clones preferentially expressed in early placenta. From a total number of recombinant clones estimated at 32,000 in the subtracted library, 594 inserts were analyzed by Southern blot and 21 sequences were isolated as corresponding to genes highly expressed in early placenta. Eleven encoded known molecules, such as carcinoembryonic antigen, human chorionic gonadotropin, and mitochondrial rRNAs. Ten sequences represented novel genes. Northern blot analysis confirmed that most of these genes were preferentially expressed in early trophoblast in comparison to terminal placenta. Three clones that gave detectable hybridization signals on total RNA were extensively studied and were found to be overexpressed in various tumors. Two of these clones, designated B9 and E4, were later identified as corresponding to genes coding for the putative ribosomal protein S18 and the bifunctional enzyme ADE2H1 involved in purine biosynthesis, respectively. Expression of the third clone, E9, was increased up to 10-fold in breast cancer tissues in comparison with normal counterparts. Present results confirm that many genes expressed in the trophoblast are overexpressed in malignant cells. This approach could provide a general targeted method for the identification of genes overexpressed in various neoplastic cell types.

Base Sequence↗
PubMed1993

Immunohistochemical study of adrenocortical carcinoma. Predictive value of the D11 monoclonal antibody.

BACKGROUND: The diagnosis of adrenocortical carcinoma (ACC) may be difficult with conventional light microscopy, especially when the tumor is nonfunctioning. Until now, no specific adrenocortical tumor marker was available. The current study was undertaken to investigate the interest of the D11 MoAb for the diagnosis and prognosis of ACC. METHODS: Eighteen adrenocortical carcinomas, 10 primary adrenomedullary tumors, 20 primary hepatocellular carcinomas, 50 primary renal cell carcinomas, 5 primary lung carcinomas, and 18 intraadrenal metastases were analyzed immunohistochemically with the D11 monoclonal antibody. ACC were also evaluated for the expression of other tumor markers, including neuron-specific enolase, chromogranin A, S-100, Leu-7, vimentin, KL1, AE1AE3, and epithelial membrane antigen. Relationships between clinical features and results of immunohistochemistry were also sought. RESULTS: Nuclear D11 staining appears to be highly specific for normal adrenocortical cells and related tumors. Nuclear D11 positivity was demonstrated in 44% of ACC and was restricted to well-differentiated tumors. No cytoplasmic or nuclear D11 staining was observed in adrenomedullary tumors. D11 reactivity confined to the cytoplasm was found in 5 of 18 adrenal metastases, in all 20 hepatocellular carcinomas tested, in 3 of 5 lung carcinomas, and in 1 of 50 primary renal cell carcinomas. Patients with nuclear D11 immunostaining were initially seen with metastases less often and survived longer than those with no nuclear D11 immunostaining (P < 0.05). CONCLUSIONS: Nuclear D11 immunoreactivity may help to differentiate ACC from intraadrenal metastases and adrenomedullary tumors. This also selects a group of ACC patients with a more favorable outcome.

Adolescent↗
PubMed1993

Apoptosis induced in Burkitt's lymphoma cells via Gb3/CD77, a glycolipid antigen.

Gb3/CD77 is a glycolipid antigen, specifically expressed on two different B-cell populations, Burkitt's lymphoma and a subset of tonsillar B-lymphocytes located in germinal centers, which could be the normal counterpart of Burkitt cells. Both Gb3/CD77(+) populations have recently been shown to enter programmed cell death (apoptosis) readily. Here we show that verotoxin, also called Shiga-like toxin, which is known to bind to the carbohydrate moiety of Gb3/CD77, induces cell death in Gb3/CD77(+) Burkitt's lymphoma cells, not only by inhibiting protein synthesis as classically described but also through an additional mechanism, namely apoptosis. Furthermore a recombinant B-subunit of verotoxin, which carries only the binding property of the holotoxin, also induces apoptosis in Gb3/CD77(+) cells. Gb3/CD77 could thus represent the first example of a glycolipid antigen able to transduce a signal leading to apoptosis.

Antigens, CD↗
PubMed1993

Cytogenetic characterization of a new human papillary thyroid carcinoma permanent cell line (GLAG-66).

A new permanent cell line (GLAG-66) has been established from the metastases of a papillary thyroid carcinoma in a male patient. Herein are reported the cytogenetic characteristics of this new cell line, which is tumorigenic in athymic mice. An aneuploid chromosomal pattern was observed (48 chromosomes) with various chromosomal abnormalities. The karyotype was: 48,XY,der(1)t(9;1;9), +der(8)t(1;8),der(9)t(1;9),der(9)t(1;9), +14. This cell line should prove to be of great value in the study of the biology of human papillary thyroid carcinomas.

Aneuploidy↗
PubMed1992

[Neuroendocrine tumor of the trachea of the intermediate type. Value of its individualization].

Tracheobronchial neuroendocrine tumours can be divided into 4 main groups: typical carcinoid; well-differentiated neuroendocrine carcinoma (atypical carcinoid); neuroendocrine carcinoma of the intermediate type, and small-cell carcinoma. Typical and atypical carcinoids are differentiated tumours, whereas intermediate neuroendocrine tumours and small cell carcinomas are little or not differentiated. Morphological or architectural criteria usually suffice to distinguish between carcinoid tumours and small cell carcinomas. In some cases, however, the neuroendocrine nature of poorly differentiated and non-small cell carcinomas is suggested by morphological criteria, but it can be confirmed only by immunohistochemistry and electron microscopy. Tracheobronchial neuroendocrine tumours of the intermediate type have been studied from a first, well-documented clinical case which demonstrated two important points: the prognosis of these tumours seems to be worse than that of carcinoid tumours, and they favourably respond to chemotherapy. In view of the therapeutic consequences, it is necessary to investigate, by the appropriate techniques, the neuroendocrine nature of these poorly differentiated carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Two-subunit structure of the human thyrotropin receptor.

The extracellular and intracellular domains of the human thyrotropin receptor were expressed in Escherichia coli and the proteins were used to produce monoclonal anti-receptor antibodies. Immunoblot studies and immunoaffinity purification showed that the receptor is composed of two subunits linked by disulfide bridges and probably derived by proteolytic cleavage of a single 90-kDa precursor. The extracellular alpha subunit (hormone binding) had an apparent molecular mass of 53 kDa (35 kDa after deglycosylation with N-glycosidase F). The membrane-spanning beta subunit seemed heterogeneous and had an apparent molecular mass of 33-42 kDa. Human thyroid membranes contained a 2.5- to 3-fold excess of beta subunits over alpha subunits. Immunocytochemistry showed the presence of both subunits in all the follicular thyroid cells, and both subunits were restricted to the basolateral region of the cell membrane.

Amino Acid Sequence↗
PubMed1992

[Neuroendocrine tumors].

The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. This is being replaced by other classifications based on results of modern techniques: secretory granules shown by electron microscopy, neuroendocrine tumour markers (NSE, chromogranin A, NPY ... ) shown by immunocytochemistry and blood measurements. Most endocrine tumours are single and sporadic, but in some patients they are multiple and/or occur as a familial disease such a multiple endocrine neoplasia or other disease, the transmission of which is autosomal dominant. This permits a more reliable classification of tumors, that can be used to determine their prognosis and response to therapy.

Biomarkers, Tumor↗
PubMed1992

Cytogenetic studies on 19 papillary thyroid carcinomas.

Short-term cultures from 19 papillary thyroid adenocarcinomas revealed clonal numerical and/or structural chromosomal changes in 13 tumors, nonclonal abnormalities in one tumor, and only normal karyotypes in five tumors. Clonal abnormalities of chromosome 10 were present in three tumors, two of which had the translocation t(7;10)(q35;q21). Numerical abnormalities of chromosome 17 were detected in two tumors.

Adenocarcinoma, Papillary↗