Biomedical subjects

F Flamant

Publications and source records attributed to F Flamant.

At least 37 records · Page 2Linked to original sources

PubMed1994

Virofection: a new procedure to achieve stable expression of genes transferred into early embryos.

A new procedure, virofection, designed to stabilize the expression of transfected DNA has been developed. It exploits the capacity of retroviruses to integrate their genome into the chromosomes of host cells. The co-transfection of two plasmids, one carrying the genome of a defective retrovirus vector, the other one encoding all the retroviral proteins, results in a transient production of infectious virus particles. These particles can infect the neighboring cells and this leads to the stable integration of the vector genome. This procedure is time-saving and appears to be quite efficient. When applied to chicken embryonic fibroblasts cultured in vitro, it resulted in the stable expression of the lacZ gene in more than 30% of the cells, and did not induce chronic viremia. Stable lacZ expression was also achieved in chicken embryos in ovo. Virofection appears to be a promising and generally applicable method for implementing stable, safe and efficient gene transfer in vitro and in vivo.

Animals↗

PubMed1994

[Pneumothorax revealing pneumoblastoma in an infant].

BACKGROUND: Pulmonary blastoma is a tumor with bad prognosis that is exceptionally seen before the age of 2 years. CASE REPORT: A 3 1/2 month-old infant was admitted because she suffered from tachypnea. A left pneumothorax with shift of the mediastinum was recognized that required insertion of a chest tube followed by ventilation and pleural drainage. X rays and CT scan showed a round bullous lesion in the left lung that persisted at the age of 5 months. At that time, clinical deterioration led to thoracotomy allowing excision of a bullous tumor; histological examination showed that this tumor was a pulmonary blastoma. Recurrence of this tumor, 16 months later, required chemotherapy and surgical excision. The patient is normal at the age of 4 years. CONCLUSION: Pulmonary blastoma is exceptional in infancy; it may be revealed by pneumothorax. Its bad prognosis requires aggressive therapy.

Diagnosis, Differential↗

PubMed1994

[The role of brachytherapy in the therapeutic strategy of vesico-prostatic rhabdomyosarcoma in children].

Because of its ballistic and physical characteristics, brachytherapy (BT) represents the optimal irradiation treatment in pediatric tumors, especially in prostate or bladder rhabdomyosarcoma. In a limited series of 15 children treated with BT (including three patients treated with salvage BT), 8 out of 9 patients surviving with NED benefited from conservative treatment among 12 patients treated with BT as first-line treatment. Sequelae were minimal consisting of one grade I cystitis and one asymptomatic vesical and ureteral reflux. BT allows administration of high doses to limited volumes sparing normal tissues. BT--whenever possible--represents the treatment of choice compared with external radiotherapy. Indications of BT depend on tumor accessibility and size (usually < or = 4 cm).

Adolescent↗

PubMed1993

Radiotherapy after ovarian transposition: ovarian function and fertility preservation.

The outcome of ovarian function preservation and fertility after ovarian transposition was examined in women treated for cancer. Of 134 patients, 126 were treated with radiotherapy and 72 with chemotherapy. In a multivariate analysis, three factors appeared to be prognostic of ovarian castration: the age over 25, MOPP chemotherapy and a total dose to the ovaries higher than 5 Gy. The incidence of birth was lower in the general population but no abnormality was observed.

Adolescent↗

PubMed1993

Screening for germ line p53 mutations in children with malignant tumors and a family history of cancer.

We have undertaken a routine investigation of the p53 status for all the children treated at our institution either affected by multiple tumors or whose family displays at least one second degree relative or less, affected by cancer before the age of 45 years. We report here on the first set of ten such families, eight of which were identified through a proband with sarcoma. p53 exons 5 to 8 have been sequenced following polymerase chain reaction amplification performed on DNA isolated from total blood. A missense mutation affecting codons 248, 273, and 282 was identified in three families. The mutation was inherited in these three families and was detected in unaffected members. In seven families no mutation was detected in exons 5 to 8.

Adolescent↗

PubMed1993

Translocation t(11;19) (q23;p13) in a child with myelomonocytic leukemia following 2 years after chemotherapy for pneumoblastoma.

A child, who received successful chemotherapy for pneumoblastoma, developed a myelomonocytic leukemia with translocation t(11;19)(q23;p13) 2 years later. Although this leukemia did not present with features generally associated with therapy-related leukemias, we think this hematologic disease to be secondary to previous chemotherapy. Involvement of chromosome 11q23 is common in acute leukemia and seems to be more significantly related to ANLL in young children (M4 and M5 FAB classification). However, our observation and previous reports suggest that this chromosomal abnormality might be more frequent in therapy-related leukemias. The responsibility of etoposide and cisplatin may be discussed in such secondary malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Treatment of non-metastatic, non-seminomatous malignant germ-cell tumours in childhood: experience of the "Société Française d'Oncologie Pédiatrique" MGCT 1985-1989 study.

The members of the French Society of Pediatric Oncology treated, between January 1985 and June 1989, 67 cases of non-metastatic, non-seminomatous malignant germ cell tumours (nSGCT) in sites other than the brain. They used a clinical pre- and postsurgical TNM-type classification in order to standardize the treatment regardless of tumour site. The intensity of the treatment was decreased in comparison with the previous regimen (elimination of adriamycin, reduction in the length of treatment). The actuarial 2-year disease-free survival rate is 80%; results are excellent for patients with clinical stage I and II tumours and permit cure with moderate chemotherapy, avoiding undesirable late effects. On the other hand it is inadequate for patients with stage III suggesting that the initial chemotherapy should be intensified for these latter patients in future protocols.

Actuarial Analysis↗

PubMed1993

Primitive malignant nonepithelial hepatic tumors in children.

Primary intrahepatic malignant nonepithelial tumors are very rare in children and account for 2% of all malignant mesenchymatous tumors under the age of 15 years. Clinical presentation, radiologic features, and histologic types are not unequivocal. The predominant role of surgery takes place either initially in small localized tumors or later, after initial reductive chemotherapy. In all cases, complete resection is the necessary but not sufficient condition for cure. Additional radiotherapy seems ineffective. High-dose chemotherapy and/or liver transplantation can be proposed for resistant cases. The disease-free survival rate is 37% at 2 years for the whole series.

Adolescent↗

PubMed1993

Use of helper cells with two host ranges to generate high-titer retroviral vectors.

We have recently described Avian Leukosis Virus (ALV)-based packaging cell lines that can produce helper-free ALV-based retrovirus vectors with A, B, C, and E envelope host ranges. Here, we report that lacZ retroviral vectors of subgroup C or E can infect helper cells of subgroup A (Isolde) which are then able to produce high titers of lacZ recombinant viruses of subgroup A. Superinfection of helper cells by lacZ recombinant virus was performed by cocultivating packaging cells with two subgroup specificities (A and E), but this did not result in increased recombinant virus titers. This "ping-pong" process caused the emergence of replication-competent (RC) viruses which are shown to result from recombination between the viral sequences of the helper cell lines and the cis-acting sequences of the lacZ recombinant virus.

Avian Leukosis Virus↗

PubMed1993

Bone metastases as the presenting manifestation of rhabdomyosarcoma in childhood.

Rarely, rhabdomyosarcoma can present with bone pain and bone lesions on radiographs without evidence of a primary tumor. Of 428 children with biopsy-proven rhabdomyosarcoma, four presented with radiographic evidence of bone metastases, but no primary tumor was found on subsequent evaluation. On radiographs, these metastases, located most commonly in the metaphyses of the extremities and in the spine, displayed a destructive or diffusely permeative pattern without sclerotic margins and mimicked the more common neuroblastoma. One patient also had diaphyseal cortical lytic metastases of the tibia. Radiographs defined metastases of the extremities better than the correlative bone scans. In the spine, on T2-weighted magnetic resonance (MR) images, metastases displayed high signal intensity which contrasted with the low-signal-intensity marrow in these pediatric patients. On histopathologic examination, metastatic rhabdomyosarcoma was composed of small cells of variable size, shape, and growth pattern similar to other round cell tumors. A positive desmin immunohistochemical test helped to establish the diagnosis. The radiologist, pathologist, and clinician should be aware of this unusual presentation of rhabdomyosarcoma so that suitable immunohistochemical tests are performed and appropriate chemotherapy given.

Adolescent↗

PubMed1993

Importance of 3' non-coding sequences for efficient retrovirus-mediated gene transfer in avian cells revealed by self-inactivating vectors.

Avian leukosis virus-derived vectors were constructed with an internal transcriptional promoter and various 3' non-coding sequences. Deletions were introduced into the downstream U3 long terminal repeat (LTR) to obtain self-inactivation of LTR-mediated transcription after one round of replication. However, 3' non-coding sequences appeared to determine not only self-inactivation of the vectors but also gene transfer efficiency. Further analysis revealed the influence of these sequences on both internal gene expression and RNA packaging. One construct permitted gene transfer while inactivating 5' LTR-promoted transcription.

Animals↗

PubMed1993

[Arterial lesions after radiotherapy in children. Apropos of 16 cases].

BACKGROUND: Arterial occlusive disease is an uncommon and rather unpredictable complication of radiotherapy in childhood. CASE REPORTS: Sixteen children (10 under 5 years of age and 7 under 3 years of age) who underwent radiotherapy for tumors between 1967 and 1983 developed an arterial occlusion with clinical manifestations during their follow-up. The radiotherapy dose was 25-55 Gy, and the fractionation was "conventional". The clinical manifestations depended on the site of arterial stenosis, including aorta and/or its branches (11 cases), carotid artery (3 cases) and limb arteries (2 cases). The delay before onset of clinical manifestations was variable, but generally very long (median: 13 years). Eight patients required surgical rehabilitation. CONCLUSION: Better management of this type of complication should benefit from the early screening of irradiated children, especially young children, given even moderate doses, and particularly those having received more than 40 Gy.

Aorta, Abdominal↗

PubMed1992

XY sex reversal associated with a deletion 5' to the SRY "HMG box" in the testis-determining region.

The human testis-determining factor resides within a 35-kilobase (kb) region of the Y chromosome immediately adjacent to the pseudoautosomal boundary. A candidate gene for human sex determination (SRY) was isolated in this region. Here, we describe a study of 25 cases of XY females with pure gonadal dysgenesis for mutations on the Y chromosome short arm, including SRY. Southern blotting revealed a sex-reversed female harboring a deletion extending from approximately 8 kb from the pseudoautosomal boundary of the Y chromosome to at least 33 kb and no more than 60 kb upstream, toward the centromere. The deletion begins no more than 1.8 kb upstream from the first ATG of the SRY open reading frame present in the clone pY53.3. To our knowledge, no mutation has been described previously outside the SRY "HMG box" on the short arm of the Y chromosome, which is associated with sex reversal. Since the 5' extent of the SRY transcriptional unit has not been defined, the deletion may remove upstream exons of SRY and/or transcriptional regulatory motifs, either situation resulting in lack of testicular development. It cannot be formally excluded that the mutation removes a second locus, independent of SRY, that is critical for sex determination. Denaturant gradient gel electrophoresis analysis of the SRY open reading frame in the remaining 24 cases revealed de novo single base-pair transitions in the SRY conserved domain in 4 cases.

Amino Acid Sequence↗

PubMed1992

Results of the LMT81 protocol, a modified LSA2L2 protocol with high dose methotrexate, on 84 children with non-B-cell (lymphoblastic) lymphoma.

From May 1981 to June 1989, 84 children with non-B-cell lymphoma (82 lymphoblastic, 1 T-cell immunoblastic, 1 unclassified diffuse lymphoma) were treated in the pediatric department of the Institut Gustave Roussy according to a protocol called LMT81, which was derived from the LSA2L2 protocol of Wollner and modified by the adjunction of 10 courses of high dose methotrexate to improve the CNS prophylaxis. No planned irradiation was performed except in cases of initial tests (2 patients) or CNS (5 patients) involvement and residual mass (2 patients). Sixty patients had mediastinal involvement; for the others, primaries were in the head and neck (7), nodes (2), (sub)cutaneous (4), bone (7), and elsewhere (2). According to Murphy's staging system, there were 2 stage I, 6 stage II, 33 stage III, and 43 stage IV. Among the stage IV patients, 41 had bone marrow involvement, 24 of them with more than 25% blast cells in bone marrow and 19 with blast cells in blood; 7 had CNS involvement. Three patients did not achieve complete remission, 4 died in remission (two measles, one post-transfusion AIDS, one unexplained definitive aplasia) and 13 relapsed at 2 to 29 months (median-13 months). Among the 77 patients without initial CNS involvement, there was only one isolated CNS relapse. With a median follow-up of 57 months (10-106 months), the event-free survival is 75% (SE 2.5) for the 84 patients with a plateau at 29 months, 73% (SE 8) for stage I and II patients, 79% (SE 4) for stage III, and 72% (SE 4) for stage IV patients. Survival was similar in each stage group. Reasons for failure of treatment, however, were different, being toxic deaths in stage II; initial therapy resistance, early relapses, and toxic deaths in stage III; and tumor failures in stage IV. In conclusion, this protocol is efficacious on T and non-T, non-B childhood lymphoma with a low incidence of CNS relapse. A future study will seek to diminish toxicity and long-term sequellae while at least maintaining the same cure rate of patients.

Adolescent↗

PubMed1992

Metastatic rhabdomyosarcoma and histologically similar tumors in childhood: a retrospective European multi-center analysis.

This is a retrospective analysis of children with metastatic soft tissue sarcoma (STS) registered in the major European STS studies: the SIOP MMT 75, the German CWS 1981 and 1986 studies, the Italian STS study, and the United Kingdom Children's Cancer Study Group centres in Britain. One hundred forty-six patients out of 164 were evaluable in this analysis. The median age was 7 years (1-18) and the male/female ratio was 1.3:1. The median follow-up was 80 months (7-171). The most common site of the primary tumor was the extremity (28%), which correlated well with the high preponderance (39%) of the alveolar type of RMS (aRMS). There was no dominant combination of metastatic sites and the most common single organ with metastasis was the lung (41%). Since the therapy depended on the country and period in which the patient was treated, we did not analyse the outcome and therapy together. Complete remission was achieved in 50% of the cases. Those with aRMS had a good chance of achieving CR (61%) but the majority of these patients relapsed (78%). The median time needed to relapse was 243 days (53 days to 47 months) for all patients. Analysis of the site of the primary tumor showed that the CR rate was best in the GU non-BP site (62%) and worst in PM cases (35%). The overall survival and DFS rate were 18% and 15%, respectively. The GU non-BP patients had a DFS rate of 50%, while the rate for all other sites varied between 12% and 18%. A total of 24 patients remained in CCR. The majority of them had embryonal type of RMS and metastases in only one anatomic site. Our analysis indicates that the best chance of prolonged survival was in metastatic GU non-BP cases, patients with embryonal type RMS, and those with metastases in only one organ. To try to improve the treatment of metastatic STS, a prospective European cooperative study was started in 1989.

Adolescent↗

PubMed1992

Preservation of ovarian function by ovarian transposition performed before pelvic irradiation during childhood.

Ovarian transposition in adults has been shown to protect ovarian function in about 60% of cases by reducing ovarian exposure to less than 4 to 7 Gy. We therefore evaluated the effect of ovarian transposition during childhood or adolescence. Eighteen girls had ovarian transposition performed at a mean (+/- SEM) age of 9.4 +/- 1.2 years (range, 1.2 to 16 years). Twelve were prepubertal and six had menstruated at the time of ovarian transposition. The initial abnormalities were Hodgkin disease (5 cases), iliac Ewing sarcoma (3), medulloblastoma (2), ovarian seminoma (1), and vaginal or uterine tumor (7). The irradiation was external in 11 cases and local by vaginal curietherapy in 7 cases. Fifteen girls received chemotherapy. The ovarian transposition was bilateral in 15 patients and unilateral in 3 cases; in the latter the other ovary had been destroyed by the tumor or by abdominal irradiation. Ovaries were placed just below the iliac crest (15 cases) or posterolateral to the uterus (3); thus, the calculated ovarian radiation dose was up to 9.5 Gy. At the time of evaluation (8.6 +/- 0.9 years after ovarian transposition), 16 girls had menstruated and 2 remained amenorrheic because of major lesions of the vagina and uterus caused by the vaginal curietherapy. Basal plasma gonadotropin values were normal. Ovulation was documented in seven cases. Two pregnancies occurred. Complications of ovarian transposition were present in four patients: intestinal occlusion, dyspareunia, functional ovarian cysts, and pelvic adhesions with tubal obstruction. We conclude that ovarian transposition, performed before abdominopelvic irradiation during childhood, can preserve ovarian function. Longer follow-up is required to assess the risk of ovarian dystrophy because of vascular lesions or chemotherapy.

Adolescent↗

PubMed1992

Packaging cells for avian leukosis virus-based vectors with various host ranges.

Using our previously described Haydée semipackaging cell line (F. L. Cosset, C. Legras, Y. Chebloune, P. Savatier, P. Thoraval, J. L. Thomas, J. Samarut, V. M. Nigon, and G. Verdier, J. Virol. 64:1070-1078, 1990) which produces avian leukosis virus gag and pol proteins, we have constructed packaging cells with subgroups B, C, and E envelope specificities. This allows us to produce helper-free avian leukosis virus particles carrying the lacZ reporter gene and the A, B, C, or E subgroup specificities. Titers of the recombinant lacZ virus are shown to be dependent upon the type of the env subgroup and the target avian cell.

Animals↗

PubMed1992

Identifying genes involved in the variability of genetic fatness in the growing chicken.

A precise knowledge of the genome involved in the expression of a quantitative trait could provide a useful tool in breeding programs; molecular genetic methods are capable of yielding this kind of information. An experimental procedure is presented here for identifying genes whose expression is related to weight variability of abdominal adipose tissue in the growing chicken. Quantitative traits are the result of metabolic pathways exhibiting some major regulation stages that are controlled genetically. These steps involve genes that may act as "major genes". With regard to chicken fat metabolism, most fatty acids are synthesized in the liver and incorporated into very low density lipoprotein (VLDL) particles before their secretion into the plasma. Accordingly, the present study focused on the expression of liver genes. The mRNA of lipogenic enzymes (acetyl-coenzyme-A carboxylase, fatty acid synthase, malic enzyme, and delta 9-desaturase) were analyzed. Also studied were apoprotein (apo)A1, apoVLDL-II, and apoB mRNA from 9-wk-old male chickens from two lines selected for high and low abdominal fat pads. Significant differences for apoA1 mRNA levels occurred between fat and lean birds. Moreover, the total quantity of mRNA provided an accurate estimation of the abdominal fat pad (r = .74 with P < .05).

Adipose Tissue↗