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Y J Bignon

Publications and source records attributed to Y J Bignon.

At least 109 records · Page 6Linked to original sources

A single Cys706 to Phe substitution in the retinoblastoma protein causes the loss of binding to SV40 T antigen.

Most naturally occurring mutants of the retinoblastoma (RB) protein contain large deletions or truncations. The small cell lung carcinoma cell line H209 contains a normal-sized but unphosphorylated RB protein (Hensel et al., Cancer Res., 50: 3067-3072, 1990), which fails to form a complex with SV40 T antigen, suggesting that the RB gene of H209 may contain a subtle mutation. To define this mutation, the RB complementary DNA and genomic DNA were sequenced, revealing a point mutation in exon 21 that changed a G to a T. This results in an amino acid substitution of a Phe for Cys706. The mutant RB complementary DNA was used as a template for in vitro transcription and translation to synthesize the mutated protein. The resulting protein failed to bind to SV40 T antigen, demonstrating that a single missense mutation of the RB gene led to the complete inactivation of the ability of the RB protein to bind T antigen.

Amino Acid Sequence↗

Evidence of 3 beta-hydroxysteroid dehydrogenase activity in several murine embryonal carcinoma cell lines.

This report describes, for the first time to our knowledge, a possible steroidogenic activity in established murine embryonal carcinoma cell lines (PCC3, PCC4, F9), revealed by a 3 beta-hydroxysteroid dehydrogenase activity (revelation of NADH2 by staining, and RIA assessment of delta 4-androstenedione). The remarkable analogy between such totipotent cells and embryonal cells may suggest that this activity could be present before histologic organization of the embryonal testis. Nonmalignant embryonal cells such as fibroblasts (3/A/1/D-3) or myoblasts (T984) were also found to possess a 3 beta-hydroxysteroid dehydrogenase activity, thus suggesting that this enzyme is not specific to hormone-secreting cells, but the sign of a more general phenomenon.

3-Hydroxysteroid Dehydrogenases↗

Molecular biology diagnosis in oncology.

The applications of molecular biology diagnosis in oncology are presented and discussed. These are: improved nosologic definition; diagnosis of clonality; definition of new prognosis subgroups in some cancers; as an aid in bone marrow transplantation follow-up; diagnosis of the residual disease; early diagnosis of cancer; evaluation of individual cancer risk.

Bone Marrow Transplantation↗

[Current role of oncostatic chemotherapy in malignant testicular tumors].

Recent results with the therapeutic strategy for malignant testicular tumors are presented. Nearly 80% of these tumors can be cured by the coordinated therapeutic efforts of a surgeon and medical oncologist. Cis-platinum chemotherapy regimens are widely used and intensive chemotherapy followed by autologous bone marrow transplantation should enable to cure poor prognosis forms in the near future.

Antineoplastic Combined Chemotherapy Protocols↗

[Therapeutic problems posed by hemiballism of metastatic origin].

A 40 year old woman undergoing treatment for cancer of the breast presented with metastatic hemiballism. Diagnosis was supported by the presence of bone and liver metastases and by CT-scan showing an enhanced rapidly growing lesion in the subthalamic region contralateral to hemiballism. Treatment by corticotherapy and neuroleptics was ineffective. Radiotherapy was unsuccessful. Metastatic hemiballism is a rare disease with no effective treatment.

Adult↗

Angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) and sicca syndrome.

We report a case of AILD and sicca syndrome. The patient had presented with renal insufficiency, lymphadenopathy, hepatosplenomegaly, polyclonal hypergammaglobulinaemia, dryness of the eyes and mouth. Lip biopsy specimens showed an unusual cellular infiltrate similar to his kidney lesions. Data from the eight previously reported cases support the hypothesis that the association is a distinct pathological entity differing from pseudolymphoma and malignant lymphoma, which occur in the course of Sjögren's syndrome. The recognition of AILD is important because lymphoproliferation may lead to death after a few months.

Aged↗

Oncogenes.

Oncogenes or genes involved in malignant development are presented. Detection procedures, gene activation, action mechanisms, and problems involving gene molecular function as well as precise role of oncogenes are discussed.

Animals↗

Systemic diffusion including germ cells after plasmidic in utero gene transfer in the rat.

OBJECTIVES: The integration of a proviral plasmid into the host genome could be a good approach for fetal somatic gene transfer. The goal of this study was to assess the integration and transcription of a proviral marker gene injected intraperitoneally into rat fetuses as well as the risks of maternal contamination and germ-line transmission. METHODS: On day 17 post-coitus, each fetus was injected intraperitoneally with 10 microg plasmid DNA through the uterine wall. Twenty-one days after spontaneous delivery, integration and transcription of the plasmid in gonad, gut, liver, spleen, lung and brain tissue from 10 pups were determined by PCR and RT-PCR. RESULTS: 14 of 60 organs exhibited integration of the plasmid. Four samples of gut (40%), 3 samples of liver and spleen (30%), 2 samples of brain (20%) and no sample of lung were transfected. Two testicular samples were transfected and study of F1 rats from 2 brothers of one of the positive rats revealed transgenic pups from 1 of these 2 animals. No transfection of maternal tissues was detected. CONCLUSION: Integration and transcription of a marker gene injected intraperitoneally into rat fetuses appear efficient, especially in intraperitoneal organs. The risk of maternal contamination appears very low when using a naked DNA plasmid injected directly into fetuses. However, germ-line contamination can occasionally occur even with injection late during pregnancy, suggesting further studies are necessary to assess this risk in direct gene transfer experiments.

Animals↗

Evaluation of the 5' spliced form of human cathepsin B mRNA in colorectal mucosa and tumors.

To evaluate the 5' spliced form of human cathepsin B mRNA in colorectal mucosa and tumors, we have determined the ratio of the spliced form for the exon 2/the complete form of cathepsin B mRNAs obtained by RT-PCR. Such ratio is significantly higher in colorectal tumors than in colorectal mucosa (p < 0.05, Kruskal-Wallis test) or in skeletal muscle (p < 0.05). Moreover, 2-fold more complete form than the spliced mRNA was found in the tumors than in the colorectal mucosa. Our data indicate that the alternative splicing of human cathepsin B mRNA in the 5'UTR may be considered as an indicator of the cellular transformation, in colorectal cancer.

Alternative Splicing↗

Time elapsing from cancer diagnosis and anxiety in women attending cancer genetic clinics.

The aim of this study was to investigate the effects of cancer genetic consultations on feelings of anxiety in women with breast/ovarian cancer. Among the 138 women attending six French clinics during a one-year period, 115 (83.3%) answered pre- and post-consultation questionnaires. The state anxiety score (Spielberger's STAI) was lower (paired t-test, p<0.001) after the consultation (34.7 9.4) than before (38.8 10.5). The time elapsing since cancer diagnosis (r=-0.28, p=0.007) was the main predictor of the decrease in anxiety. The patients consulting earlier after their cancer was diagnosed were more anxious before the consultation than those consulting later: whereas their anxiety states after the consultation were similar. The consultation effectively decreased the anxiety observed and the anxiety felt by cancer patients before the consultation may constitute an anticipatory stress response that should be investigated.

Anxiety↗

Electrophoresis of BRCA1 oncosuppressor.

BRCA1 is a familial breast and ovarian cancer susceptibility gene and encodes proteins that function as tumor suppressors in human breast cancer cells. To elucidate the biological function of BRCA1, knowledge of cellular localization is needed. This can be achieved by using specific antibodies, so in a first step, we characterized by Western blot analysis the rabbit polyclonal antibodies (K-18) and (D-20) raised against the amino-terminus of human BRCA1 protein, and the polyclonal antibodies (C-20) and (I-20) raised against the carboxy terminus of human BRCA1 protein. The 220-kDa band corresponding to BRCA1 protein was recognized by the four tested antibodies in two mammary carcinoma cell lines (HBL100 and MCF7).

Blotting, Western↗

Allelic imbalance at NBS1 is frequent in both proximal and distal colorectal carcinoma.

Nijmegen breakage syndrome (NBS) is a hereditary disorder involving chromosomal instability, cancer risk and radiosensitivity. NBS carriers have an increased risk of cancer, though the significance of mutations in the NBS1 gene in sporadic cancer has not yet been investigated. Because the loss of NBS1 is associated with increased chromosomal re-arrangements, and tumors of the colon are particularly prone to chromosomal anomalies, we have begun to study the NBS1 locus in colorectal cancer (CRC). DNA was isolated from 99 microdissected colorectal tumors, and microsatellite markers flanking the NBS1 locus at 8q21.3 as well as elsewhere on 8q were analyzed. Normal lymphocyte DNA from each patient served to normalize the amplification of each allele, and a reduction of at least 35% in the intensity of one allele was taken as evidence of allelic imbalance (AI). In proximal and distal CRCs we found 25.9 and 36.2% with AI at 8q21.3, respectively. AI in proximal CRC tended not to extend to marker D8S555 at 8q24.1, whereas in distal CRC the region of AI frequently included all the informative markers. AI of 8q21.3 was not associated with any clinical variable. These results suggest that 8q21.3 contains a tumor suppressor gene involved in proximal CRC, possibly NBS1. The large regions of AI make it difficult to determine the importance of AI at the NBS1 locus in distal CRC.

Alleles↗

Characterization of anti-BRCA2 antibodies in cell lines by Western blot analysis.

BRCA2 is a tumor suppressor gene associated with familial predisposition to breast and ovarian cancer. BRCA2 has been implicated in response to DNA damage, cell cycle control and transcription. However, the mechanisms by which the BRCA2 protein suppresses tumor cell growth are largely unknown. To begin to understand the contribution of BRCA2 protein to tumorigenesis, we evaluated the specificity of 4 anti-BRCA2 antibodies directed against several different epitopes using immunoblotting techniques. The two monoclonal antibodies (3E6 and 5F6) detected a specific 384-kDa protein in human breast cancer cell lines (MCF7 and MDA-MB 231) and in a human colon carcinoma cell line (CCL 221). The two polyclonal antibodies (9433 and 9434) recognized the 384-kDa BRCA2 protein respectively in MCF7 and in CCL 221 cells, but both BRCA2 polyclonal antibodies also cross-reacted with smaller proteins.

Antibodies↗

Specific H-Ras minisatellite alleles in breast cancer susceptibility.

Mutations in BRCA1 and BRCA2 genes account for the majority of familial aggregation of breast and ovarian cancers but other common genes in the population with low penetrance should be also involved in susceptibility to breast cancer. The H-ras minisatellite, located downstream of H-ras oncogene, is considered to be a likely candidate. Previous findings have estimated that as many as 1 in 11 cancers of the breast might be attributed to this region, but other studies observed inconsistent results. We propose to elucidate the potential role of H-ras locus in breast cancer, by looking at somatic alterations occurring in tumor DNAs such as the instability or the loss of heterozygosity (LOH) and by determining a potential correlation between constitutional specific H-ras alleles and clinical and/or pathological characteristics. DNA was extracted from 123 sporadic breast tumors and matched peripheral blood lymphocytes. 143 DNA samples from of peripheral blood lymphocytes from healthy donors served as a control population. The allelic diversity was determined by polymerase chain reaction analysis. Rare H-ras alleles were found to be present in about 9% of breast cancer patients while they were detected in only 1.4% of lymphocytes from healthy donors (P = 0.0044). Therefore, the risk of breast cancer is increased in patients with one or two rare alleles (odd ratio = 7.14 and 95% confidence interval = 1.94-22.27). Analyses of somatic alterations in tumor DNA have shown the lost of one allele, in general the longest, in 6.7% informative cases and an instability to H-ras locus in 6.5% tumors that appeared as a size increase of one of the two alleles. No correlation of rare H-ras alleles with clinicopathological parameters was found. Our results demonstrated an association of rare H-ras alleles with breast cancer and suggest that minisatellite H-ras may be considered as an informative marker for the breast cancer risk.

Adult↗