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Biomedical subjects

M Schlumberger

Publications and source records attributed to M Schlumberger.

At least 109 records · Page 6Linked to original sources
PubMed1997

Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors.

Abnormalities of the 11p15 region with overexpression of the normally imprinted insulin-like growth factor II (IGF-II) gene have been implicated in the pathogenesis of adrenocortical tumors. We evaluated the frequency and distribution of 11p15 loss of heterozygosity (LOH) and IGF-II gene overexpression in a series of 82 sporadic adrenocortical tumors, screened for pathological functional imprinting of the 11p15 region in tumors not exhibiting LOH and evaluated the expression of H19 gene in these tumors. Abnormalities of the 11p15 region as LOH (loss of the maternal allele and duplication of the paternal allele) and/or IGF-II gene overexpression are frequent features of the malignant state and were found in 27 of 29 (93.1%) of the malignant tumors and in only 3 of 35 (8.6%) of the benign tumors. Tumors without abnormality of the 11p15 region (mainly benign tumors) did not exhibit pathological functional imprinting. In tumors with mosaicism for 11p15 LOH, biallelic expression of the IGF-II gene was constant in the tumor cell contingent not undergoing LOH. Abrogation of H19 expression correlated with the loss of the maternal allele (LOH or pathological imprinting), but did not always correlate with overexpression of the IGF-II gene. These data indicate the involvement of dysregulation of the 11p15 region in late steps of adrenocortical tumorigenesis and provide us with new molecular markers for a better diagnostic and prognostic evaluation of adrenocortical tumors.

Adolescent↗
PubMed1997

Sequential biological dosimetry after a single treatment with iodine-131 for differentiated thyroid carcinoma.

UNLABELLED: To determine the cytogenetic and genotoxic risk associated with therapeutic exposure to 131I (3.7 GBq) in 50 patients with differentiated thyroid carcinoma, we estimated the dosimetric index that reflects the dose to the circulating lymphocytes on Day 4 and at several time intervals after exposure over a period of 2 yr. METHODS: Chromosomal aberrations were scored in peripheral lymphocytes obtained before and then 4 days, 3 mo, 6 mo, 1 yr and 2 yr after the first administration of 3.7 GBq 131I according to two methods: conventional cytogenetics and chromosome 4 painting. RESULTS: The dosimetric index was 0.52 Gy on Day 4, 0.49 Gy at 3 mo, 0.45 Gy at 6 mo, 0.44 Gy at 1 yr and 0.42 Gy at 2 yr by conventional cytogenetics and 0.47 Gy on Day 4, 0.45 Gy at 3 mo, 0.44 Gy at 6 mo, 0.43 Gy at 1 yr and 0.42 Gy at 2 yr by chromosome 4 painting. We found a decrease in the frequency of chromosomal aberrations between Day 4 and 3 mo after exposure. This may be due to the decrease of lymphocyte counts shortly after 131I administration, which will recover later on. In contrast, the number of anomalies remained constant starting 3 mo after 131I administration. CONCLUSION: These techniques permit retrospective biological dosimetry for up to 2 yr after therapeutic exposure to 131I.

Adult↗
PubMed1997

[Neuroendocrine tumors].

The term "neuroendocrine" designates tumors with common morphology and immuno-histochemistry characteristics whatever their localization or embryological origin. Diagnosis of neuroendocrine tumors implies: assay of markers and peptide hormones and scintigraphy examination (ostreoscan); family screening; treatment according to localization, degree of histological differentiation and extention as well as possible secretion of peptide hormones.

Antineoplastic Agents↗
PubMed1997

[Eutopic and ectopic production of glycoprotein hormones alpha and beta subunits].

Human chorionic gonadotropin (hCG) is a glycoprotein composed of two subunits, alpha and beta, linked together by a covalent bond. Ectopic production of hCG has been described in various histological types of cancer. Actually, these malignant tumors predominantly secrete the free beta subunit (hCG beta) and not hCG. Production of free hCG beta is especially found in patients with bladder, pancreas, uterine and lung tumors. In patients with neuroendocrine tumors, serum levels of free hCG beta are higher in gastrointestinal-pancreatic and lung tumors. The significance of ectopic production of hCG beta--epiphenomena or intrinsic biological role--remains unknown. Several reports on the similar structure of hCG beta and certain growth factors suggest that free hCG beta could have an effect on cell proliferation. Increased serum levels of the free alpha subunit are found mainly in patients with neuroendocrine tumors localized in the gut or lung. Serum levels may also be raised in patients with a pituitary tumor, but such production is often associated with a rise in other pituitary hormones. The free alpha subunit plays a role in embryon development and would stimulate production of prolactin by decidual cells. The free alpha subunit may also play a role in tumor growth.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1997

[Isolated mandibular metastases. Therapeutic strategy. Apropos of 7 cases].

Among the mandibular tumours, the secondary malignant tumours are uncommon. We relate 7 cases observed between 1977 and 1995. Two cases have revealed the original cancer (rectum, prostate). The five other cases were discovered during the evolution of the original cancer (colon, lung, kidney, thyroid, breast). These 7 mandibular metastases were isolated. The treatment included a mandibular resection in 6 cases. In one of these cases, the reconstruction was performed with a free vascularized fibular transplant with success. Among the seven cases, two patients are alive, at the present time, with a mean follow-up of 3 years. This justifies a curative treatment.

Adult↗
PubMed1996

[Differentiated thyroid epithelioma].

Long term prognosis of differentiated thyroid carcinoma is favourable, being modulated by several factors, age and histology being the most relevant. Initial treatment includes firstly surgery: loboisthmusectomy in case of intra-thyroid tumor, unifocal, less than 1.5 cm in diameter in patients with favourable prognostic indicators, total thyroidectomy with the administration of an ablative dose of 131l in all the other patients. A routine dissection of the paratracheal groove and of the supraclavicular area is performed in all patients. L-thyroxine treatment is given to all patients. Relapses should be discovered early; this is made possible by the combined use of serum thyroglobulin measurements and of 131l total body scans.

Carcinoma↗
PubMed1996

High frequency deletion of the tumour suppressor gene P16INK4a (MTS1) in human thyroid cancer cell lines.

p16INK4a (MTS1) is an important negative regulator of mammalian cell proliferation, acting via inhibition of CDK4/cyclin D-dependent phosphorylation of pRb to prevent progression through the G1 phase of the cell cycle. Loss of p16 activity by either gene deletion, mutation or transcriptional inactivation has now been found in a wide range of human cancers of both epithelial and mesenchymal origin, at a frequency rivalling that of p53 mutation. As a first step towards investigating its possible role as a tumour suppressor gene in thyroid tumorigenesis, we have carried out a Southern blot analysis of the p16 gene locus in a series of cell lines derived from differentiated human thyroid cancers. Homozygous deletion of the entire p16 coding sequence was observed in two of three follicular and two of four papillary cancer cell lines, but not in normal tissue or normal cells immortalised by SV40 T antigen. Given the co-existence of p16 abnormalities in primary tumours and cell lines observed in other tumour types, this high frequency of deletion suggests that p16 is a key tumour suppressor gene in the genesis of differentiated thyroid cancer.

Adenocarcinoma, Follicular↗
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

Phenotypic and functional characterisation of tumour-infiltrating lymphocytes derived from thyroid tumours.

The natural history of thyroid tumours and the hyper-reactivity of the immune system in patients with thyroid cancer suggest that immune surveillance may play a role in the control of this disease. A study was therefore undertaken to analyse the phenotypic and functional features of tumour-infiltrating lymphocytes (TILs) derived from thyroid tumours. In a series of experiments, it was found that, in contrast to TILs derived from patients with melanoma or renal cell carcinoma, thyroid TILs could be efficiently expanded in vitro only in the presence of allogeneic EBV transformed B (B. EBV) cells. Indeed, only one of the seven thyroid-derived TILs grew in vitro without feeder cells, whereas all 16 thyroid-derived TILs could be expanded in the presence of allogeneic B. EBV feeder cells. Phenotypic analysis of these TILs revealed a frequent in vitro expansion of an unusual T cell population that expressed both the CD4 and CD8 markers. Indeed, it was demonstrated that in five of 14 TILs in short-term culture (< day 23) and four of 11 TILs in long-term culture (> day 40), a lymphocyte population that coexpressed CD4 and CD8 antigen accounted for more than 15% of the total TIL population. This double-positive T cell population was not observed in TILs derived from melanoma or renal cell carcinoma. Thyroid-derived TILs also displayed an intense cytolytic activity against NK-sensitive tumour targets with 10 of 11 TILs exhibiting significant cytotoxicity towards the NK-sensitive K562 cell line. Six of 11 TILs were also cytotoxic towards autologous tumour, but when cold target inhibition with K562 was performed with three cultures, unlabelled K562 completely inhibited lysis of autologous tumour cells. A significant expansion of CD3+CD56+ T cells in the different TIL populations may explain this high level of NK-like cytotoxicity. In conclusion, TILs derived from thyroid tumours could be efficiently expanded in vitro under certain culture conditions. Different strategies must be explored to enhance their specific tumour autologous specificity, however, before they can be used in immunotherapy protocols.

Adult↗
PubMed1996

Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas.

Forty-four thyroid autonomously hyperfunctioning adenomas were analyzed to assess the frequency of mutations occurring in the TSH receptor (TSHR). PCR-amplified fragments encompassing the entire exon 10 of the TSHR gene were obtained from the genomic DNA extracted from the tumors and their adjacent normal tissues and were examined by direct nucleotide sequencing. Point mutations were found in 9 of the 44 adenomas examined (20%). One mutation occurred in codon 619 (Asp to Gly), four in codon 623 (three were Ala to Ser, one Ala to Val substitution), two in codon 632 (both Thr to Ile), and two in codon 633 (Asp to Tyr or His). All the alterations were located in a part of the gene coding for an area including the third intracellular loop and the sixth transmembrane domain of the TSH receptor. All mutations were somatic and heterozygotic, and none was simultaneous with alterations of ras or gsp oncogenes. Thus, our data show that in our series of 44 hyperfunctioning thyroid adenomas, a somatic mutation of the TSHR, responsible for the constitutive activation of the cAMP pathway, occurs in 20% of the tumors.

Adenoma↗
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↗
PubMed1996

Comparison of octreotide scintigraphy and conventional imaging in medullary thyroid carcinoma.

UNLABELLED: We evaluated the clinical utility of positive somatostatin receptor scintigraphy in patients with medullary thyroid cancer (MTC). METHODS: Twenty-four MTC patients with increased calcitonin levels underwent somatostatin receptor scintigraphy using 111In-pentetreotide (120-200 MBq) with early (4 hr after injection) and delayed (24 hr) whole-body scans and liver SPECT imaging. In Group 1 (12 patients), conventional imaging modalities demonstrated the presence of tumor sites prior to somatostatin receptor scintigraphy; in Group 2 (12 patients), conventional imaging modalities were negative or inconclusive. RESULTS: Somatostatin receptor scintigraphy had positive results in 9 of 24 patients (37%): of Group 1 patients, 7 of 12 had positive somatostatin receptor scintigraphy results. Of these patients cases, somatostatin receptor scintigraphy demonstrated several involved organs and tumor sites either identical (two patients) or smaller (five patients) in size than conventional imaging modalities. Only two patients in Group 2 had positive somatostatin receptor scintigraphy results which demonstrated significant mediastinal uptake previously classified as indeterminate on conventional imaging modalities. No new tumor site was identified nor were therapeutic options modified by the somatostatin receptor scintigraphy results. CONCLUSION: Somatostatin receptor scintigraphy only demonstrates part of tumor sites and cannot visualize small tumor sites (< or = 1 cm). We believe that somatostatin receptor scintigraphy has a limited role in the management of MTC patients.

Adult↗
PubMed1996

Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma.

UNLABELLED: We assessed the therapeutic benefits of 131I treatment in patients with distant metastases of differentiated thyroid carcinoma. METHODS: Of 2200 patients treated for differentiated thyroid carcinoma at our institution, 394 had lung and/or bone metastases. RESULTS: Two-thirds of the patients had 131I uptake in their metastases, but only 46% achieved a complete response. Prognostic factors for complete response were: younger age, presence of 131I uptake in the metastases and small extent of disease. The survival rate was 33% at 15 yr. As shown by multivariate analysis, favorable prognostic factors for survival were: younger age and time of metastases detection, well-differentiated histologic type of the thyroid tumor, presence of 131I type uptake in the metastases, small extent of the disease and year of discovery of metastases. CONCLUSION: In terms of survival, the benefits of 131I therapy cannot be demonstrated by prospective controlled studies. The present study clearly demonstrates, however, that treatment with 131I is one of the factors which accounts for survival; patients whose metastases concentrated 131I and who could be treated with radioiodine had higher survival rates. Patients who achieved complete response following treatment of distant metastases had a 15-yr survival rate of 89%, while those who did not achieve complete response had a survival rate of only 8%. The survival rate improved with the year of discovery of distant metastases, after 131I total-body imaging and serum thyroglobulin measurements were routinely used.

Adenocarcinoma, Follicular↗