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Biomedical subjects

J Michon

Publications and source records attributed to J Michon.

At least 91 records · Page 5Linked to original sources
PubMed1994

The role of chemotherapy in orbital involvement of retinoblastoma. The experience of a single institution with 33 patients.

BACKGROUND: Orbital involvement is a rare occurrence in retinoblastoma but still carries a bad prognosis. The aim of this study was to define more clearly the role of chemotherapy in this advanced disease. METHODS: Between 1977 and 1991, 33 patients were treated at the Services de Pédiatrie at Institut Curie (Paris, France) for orbital involvement of retinoblastoma, which was isolated in 20 patients and associated with metastases in 13 patients (outside the central nervous system [CNS], 6; within the CNS, 7). Treatment included chemotherapy for 33 patients, irradiation of the orbit for 23 patients, and intrathecal chemotherapy and/or CNS irradiation in selected patients. RESULTS: The plateau phase of the survival curve was reached at 15 months, with a survival of 34% plus or minus 8%. The disease free interval was longer when patients had no CNS disease (P < 0.05). Twenty of the 21 recurrences (95%) occurred within 1 year after diagnosis of orbital involvement. CONCLUSIONS: Intensive chemotherapy using cyclophosphamide, platinum compounds, epipodophyllotoxins, doxorubicin, and vincristine was effective in orbital involvement of retinoblastoma even with associated extra-CNS metastases. However, associated CNS disease still carries a bad prognosis, and long term follow-up is necessary to evaluate the risk of a second tumor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Two distinct deleted regions on the short arm of chromosome 1 in neuroblastoma.

The short arm of chromosome 1p is the most frequently altered chromosome segment in neuroblastoma. The alterations, mainly deletions, are thought to be indicative of the presence of a tumor suppressor gene. To further refine the chromosome localization of this gene, we have studied paired constitutional and tumor DNA from a series of 60 patients with neuroblastoma at 2 minisatellite and 23 microsatellite loci dispersed along the short arm of chromosome 1. Twenty-two cases (37%) demonstrated loss of heterozygosity (LOH) at one or more loci on 1p. Surprisingly, the pattern of LOH enabled the identification of two distinct consensus regions of deletions. In agreement with previous reports, one region mapped to the distal short arm of chromosome 1. The other region was localized more proximally on 1p. Deletions observed in tumors involve either one or both of these regions. We show that the correlation between NMYC amplification and 1p deletion is limited to the deletions which involve the proximal region either alone or together with the distal region. These results suggest that two tumor suppressor genes on 1p might be involved in the development of neuroblastoma. Finally, we show that somatic mutations at microsatellite loci, frequently observed in other types of cancer, are rare events in neuroblastoma.

Chromosome Deletion↗
PubMed1994

Natural and recombinant soluble low-affinity Fc gamma R: detection, purification, and functional activities.

Studies on the identification, cloning, and biochemical characterization of natural and recombinant human and mouse low-affinity soluble Fc gamma R (sFc gamma R) have been developed using various methods. RT-PCR and/or biochemical analyses have demonstrated that low-affinity sFc gamma R (i) are generated by enzymatic cleavage of membrane-associated receptors or by an alternative splicing of the transmembrane region encoding exon and (ii) comprise only the extracellular domains or these domains plus the intracellular region of the membrane-associated molecules, respectively. Functional studies indicated that recombinant sFc gamma R bind mouse and human IgG subclasses with a binding profile identical to that of their membrane counterparts and inhibit Fc gamma R-mediated functions such as immune complex binding or ADCC. In addition, it has been demonstrated that a mouse recombinant truncated sFc gamma RII inhibits antibody responses to T-dependent antigens as well as B-cell proliferation and that a human recombinant truncated sFc gamma RIIIB blocks the Ig production by activated human peripheral blood mononuclear cells. Finally, different immunoassays devised to detect and quantitate circulating sFc gamma R showed that sFc gamma R serum levels vary in circumstances such as injections of protein antigens, in parasitic infections, in tumor-bearing mice, in patients with multiple myeloma (MM), or upon infusions of IgG or Fc gamma fragments in MM or immune thrombocytopenic purpura patients. The use of recombinant sFc gamma R, as well as the availability of monoclonal and polyclonal antibodies directed against different regions of these molecules, makes it possible to characterize further the biological effects of sFc gamma R and their biochemical and immunochemical characteristics, as well as to define their putative ligands on cell membranes.

Amino Acid Sequence↗
PubMed1994

Therapy of Burkitt and other B-cell acute lymphoblastic leukaemia and lymphoma: experience with the LMB protocols of the SFOP (French Paediatric Oncology Society) in children and adults.

Burkitt's lymphoma and L3-ALL are different forms of the same disease: B-cell disease. Therapeutic improvement has been considerable over the past 10 years. In France, four consecutive multicentre LMB studies of the SFOP greatly contributed to this improvement. An overall cure rate of 90% can now be achieved in children with a short intensive risk adapted polychemotherapy regimen based on high-dose fractionated CPM, HD MTX (3 g/m2), Ara-C in continuous infusion. For patients with ALL or with CNS involvement, the addition of CNS-directed therapy with a higher dose of MTX (8 g/m2), HD Ara-C (3 g/m2 x 4), VP 16, triple intrathecal injections and cranial irradiation greatly improved survival: 87% for ALL and 73% for patients with CNS involvement. In adults, the application of the paediatric protocol is possible with acceptable toxicity and a retrospective study of 41 cases treated according to a LMB protocol showed a cure rate of 71%. Such a regimen should now be proposed to adults and studied prospectively.

Abdominal Neoplasms↗
PubMed1994

Intraorbital foreign bodies.

A high index of suspicion is important in evaluating any penetrating orbital injury. Likewise, any chronically infected orbit must be suspected of harboring an IOrbFB. Careful history and examination are mandatory for both clinical and medicolegal purposes. Appropriate imaging studies, usually including CT scanning, must be employed. Antibiotic therapy may be crucial in preventing infectious complications, including those involving the central nervous system. The decision regarding surgery must be individualized and should consider visual status, form and composition, and localization of an IOrbFB. The possibility of orbitocranial extension should always be considered and ruled out. Following these general rules, an injury with a small but real potential for clinical disaster may be mitigated, and visual and neurological outcome may be optimized.

Brain Injuries↗
PubMed1994

[Immunoradionuclide localization of human neuroblastoma xenografted in nude mice using anti-GD2 labelled with I125].

Neuroblastoma is the most frequent tumour of the childhood under the age of 5. The staging and the follow up are achieved by MIBG scintigraphy, considered as the method of reference, but sometimes difficult to interpret . The availability of monoclonal antibodies against the ganglioside GD2, expressed on the cell membrane of neuroblastoma and neuro-endocrine cancers offers novel tools that deserve to be carefully explored. We investigated four mouse monoclonal antibodies (3 IgG3: BW704, 7A4, 60C3, and the IgG1 variant of BW704: MAK704), on nude mice xenografted with a human neuroblastoma (REM). Sixty one nude mice were included. The three former MAbs provided tumour imaging, the best results being obtained with BW704, followed by 7A4 and 60C3. MAK704 was disappointing. A control antiphosphorylcholine antibody (P51-1) did not give any tumour image in the three tested mice. Scintigraphy ratios tumour/liver and tumour/muscle reached 20 and 100 with BW704, respectively, on the 10th day. Good imaging quality was already obtained from the 24th h. The tumour uptake, calculated from radioactivity countings of resected samples, reached 22 +/- 3% of injected dose per gramme. These results let us hope that these antibodies could also provide highly contrasted images in humans and could open the way for therapeutic applications.

Animals↗
PubMed1993

Safety and efficacy of mitomycin C trabeculectomy in southern India. A short-term pilot study.

PURPOSE: Glaucoma is a major cause of blindness in developing nations. Medical and laser therapy have limitations in this environment. Filtration surgery alone often fails in young, darkly pigmented, individuals. The authors, therefore, evaluated the safety and efficacy of filtration surgery, using topical mitomycin C, in patients undergoing trabeculectomy in India. METHODS: A short-term pilot study used mitomycin C at the time of trabeculectomy in a population of southern Indians with various forms of glaucoma. A single 5-minute intraoperative application of 0.4 mg/ml mitomycin C was given to 76 consecutive patients requiring filtration surgery for the control of intraocular pressure (IOP). All patients were admitted for 6 days and were seen at 6-week intervals for a minimum of 18 weeks. RESULTS: The mean preoperative IOP was 35.3 +/- 9.6 mmHg. Postoperative IOP control was attained in 93.4% of patients as defined by an IOP of 20 mmHg or less without additional glaucoma medications (or an IOP reduction > 25% if the preoperative IOP was < or = 20 mmHg). No corneal epithelial defects or wound leaks were seen. The major complications were cataract formation and a decreased visual acuity in ten (13%) eyes. CONCLUSION: Mitomycin C-aided trabeculectomy was highly successful in controlling IOP in this darkly pigmented population and may become an important adjunct in the treatment of glaucoma in developing countries.

Administration, Topical↗
PubMed1993

Growth and growth hormone secretion after bone marrow transplantation.

This study analyses the growth and the growth hormone secretion of children given various conditioning protocols before bone marrow transplantation (BMT). Twenty nine children (14 boys, 15 girls) given BMT were classified according to their conditioning protocol: total body irradiation (TBI) given as a single exposure of 10 Grays (Gy, group I, 11 cases), or 8 Gy (group II, four cases), 12 Gy given as six fractionated doses (Group III, seven cases), or chemotherapy alone (group IV, seven cases). The arginine-insulin stimulated growth hormone peak, 2-7.5 years after BMT, was > 10 micrograms/l in all patients except four from group I (6.9-8.9 micrograms/l). A second growth hormone secretion evaluation was performed in 10 group I patients because of persistent low growth velocity despite a normal growth hormone peak. There were no significant changes in the mean (SEM) stimulated growth hormone peak (18.4 (2.2) v 20.1 (3.6) micrograms/l) at 3 (0.3) to 5.2 (0.6) years after BMT. The sleep growth hormone peaks and concentrations (n = 6) were normal. The mean cumulative height changes (SD) during the three years after BMT were: -1.4 (0.2) in group I, -0.1 (0.4) in group II, -0.4 (0.2) in group III, and 1.5 (0.5) in group IV; this was significant in groups I and IV. The final heights of two monozygotic twins (BMT donor and recipient) had differed by 17.5 cm, despite them both having normal growth hormone peaks and puberty. Eight patients, treated for congenital immune deficiency syndrome, were growth retarded at the time of BMT. Of these, only those conditioned by chemotherapy alone had significant catch up growth (2(0.6)SD) while those conditioned by a single Gy exposure did not (0(0.4)SD). It is concluded that the total radiation dose is critical for growth evolution, as is the fractionation schedule. For the TBI doses and the interval since BMT studied, there was no correlation between growth hormone peak and the height loss. The rapidity of decreased growth velocity after TBI and the comparison between the monozygotic twins suggest that radiation induced skeletal lesions are partly responsible for the decreased growth.

Bone Marrow Transplantation↗
PubMed1993

Combined continuous infusion etoposide with high-dose cyclophosphamide for refractory neuroblastoma: a phase II study from the Société Française d'Oncologie Pédiatrique.

PURPOSE: Patients older than 1 year with stage IV neuroblastoma who fail to achieve complete remission (CRem) have a particularly poor long-term prognosis. In an attempt to improve the outcome of these refractory patients, we tested a new drug combination. PATIENTS AND METHODS: Twenty-nine children with advanced neuroblastoma (27 stage IV and two stage III) were entered onto this phase II study. All were refractory to conventional chemotherapy and had measurable disease at the time of the trial. The regimen was a combination of high-dose cyclophosphamide (2 g/m2/d) on days 2, 3, and 4, and etoposide (VP16; 50 mg/m2/d) by continuous intravenous (IV) infusion on days 1 to 5. A pharmacokinetic study of VP16 was conducted in eight patients to determine whether the goal of persistent plasma levels between 1 and 5 micrograms/mL was achieved. RESULTS: Patients received a median of two courses, for a total of 58 courses. The median interval between each course was 32 days. In the 28 assessable patients, the overall response rate was 43%, with one CRem and 11 partial remissions (PRems). No life-threatening complication was observed in these heavily pretreated patients. The median duration of neutropenia (< 5 x 10(9)/L) was 14 days, and that of thrombocytopenia (< 50 x 10(9)/L) was 11 days. The overall incidence of sepsis was 27%. Gastrointestinal toxicity was frequent, but mild. Electrolyte disturbance with antidiuretic hormone (ADH)-like syndrome occurred in eight courses, but resolved rapidly. Grade > or = 2 hemorrhagic cystitis was observed in three courses. No cardiac toxicity was observed. There were no treatment-related deaths. Pharmacokinetic analysis showed that mean steady-state plasma levels (Css) of VP16 were greater than 1 microgram/mL during all the courses. CONCLUSION: This new drug combination appears to be effective in advanced neuroblastoma. Its toxicity remains manageable, with no life-threatening complications. Further evaluation in patients with less-advanced disease is warranted.

Adolescent↗
PubMed1992

PCR assay for chromosome 1p deletion in small neuroblastoma samples.

Deletion of the short arm of chromosome 1 is among the most recurrent cytogenetic alterations found in neuroblastoma and has been associated with short survival. However, this prognostic information, which relies on time-consuming techniques, is not yet routinely exploited. In order to set up a reliable and simple routine test to determine 1p deletion in neuroblastoma, we have used the polymerase chain reaction to genotype neuroblastoma DNA at 2 loci containing a variable number of tandem repeats and located on the distal part of the short arm of chromosome 1. Agarose gel electrophoresis and ethidium bromide staining of the amplification products enable a simple determination of constitutional and tumor genotypes at these loci to be made. A total of 37 samples from 29 patients were studied with this technique. Loss of heterozygosity (LOH) could be identified in 8 cases. In each case the results obtained were in agreement with those achieved by the Southern procedure. This technique will be of particular interest in the pretherapeutic analysis of 1p deletions in small tumor samples obtained by fine-needle aspirates of the primary tumor. It should also enable retrospective studies from paraffin-embedded tumor fragments to be made and provide information for the analysis of tumor heterogeneity in neuroblastoma and in other tumors with 1p deletions.

Base Sequence↗
PubMed1992

Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study.

PURPOSE: A phase II study of etoposide (VP 16) and carboplatin (CBDCA) was performed in patients with metastatic neuroblastoma (NB). The aim of the study was to find an alternative treatment for induction with different toxicities than the VP 16/cisplatin (CDDP) combination. PATIENTS AND METHODS: Forty-seven patients who were from 6 months to 16 years of age, with either relapsed (29) or primary resistant (18) NB, were included in a cooperative multicenter phase II study of the French Society of Pediatric Oncology (SFOP). The schedule consisted of 5 consecutive days of VP 16 100 mg/m2/d and CBDCA 160 mg/m2/d. RESULTS: The response rate for the 39 assessable patients was 43%; there were four complete remissions and 13 partial remissions. Neither the status of the patients nor the total dose of CDDP that was received previously influenced response. Hematologic toxicity was marked and caused considerable delay between courses (median interval, 39 days). In these heavily pretreated patients, 16% had a more than 50% decrease in creatinine clearance and a 22% World Health Organization (WHO) grade 2 ototoxicity. CONCLUSION: This VP 16/CBDCA combination deserves further evaluation for efficacy and toxicity in newly diagnosed patients, and the combination of both drugs should be considered for high-dose therapy with bone marrow transplantation.

Adolescent↗
PubMed1991

Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens.

LFA-3, ICAM-1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA-3 on 20 and ICAM-1 on 10. HLA.ABC and LFA-3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA-3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM-1 was restricted to 5 of the 10 low-grade stage-1 or stage-2 specimens, 1 stage-3 specimen, and the primary tumors of 2 patients with stage-4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA-3 expressed on both mycN-negative and -positive specimens, whereas ICAM-1 was restricted to MYCN-negative specimens. LFA-3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM-1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM-1-negative, suggesting ICAM-1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN-gamma.

Alkaline Phosphatase↗