Search PubMed⌕ Search

Biomedical subjects

P Chastagner

Publications and source records attributed to P Chastagner.

At least 55 records · Page 3Linked to original sources
PubMed1997

Loss of chromosome 1p may have a prognostic value in localised neuroblastoma: results of the French NBL 90 Study. Neuroblastoma Study Group of the Société Française d'Oncologie Pédiatrique (SFOP).

Between March 1990 and December 1994, 316 consecutive children with localised neuroblastoma were registered in the French NBL 90 study. In addition to the assessment of a new chemotherapy regimen in unresectable neuroblastoma, we evaluated the prognostic significance of MYCN amplification and loss of the short arm of chromosome 1 (LOH1p). MYCN was found in 22/225 children (10%) and associated with unfavourable clinical features such as age at diagnosis > 1 year and large and unresectable tumours. LOH1p was observed in 9/91 patients (10%), of whom some had favourable prognostic factors such as age at diagnosis < 1 year (n = 4), INSS stage 1 or 2 (n = 3) and no MYCN amplification (n = 4). Overall survival (OS) and event-free survival (EFS) were, respectively, 56% and 22% (median follow-up: 36 months) for children with LOH1p compared with 97% and 94% for those without (log-rank = 10(-8)). All except 1 of the 5 children with MYCN amplification and LOH1p relapsed and ultimately died of the disease. Among the 4 with LOH1p and no MYCN amplification, recurrence occurred in 3 (2 local, 1 metastatic), all alive in second remission after salvage therapy (12-19 months after the relapse). In multivariate analysis, LOH1p was the strongest prognostic indicator for subsequent relapse. LOH1p appears more discriminant than MYCN amplification for predicting the risk of recurrence in children with localised neuroblastoma. However, its analysis was possible in only 30% of our patients and its final impact on survival should be confirmed in larger, prospective studies in order to stratify subsequent treatment.

Abdominal Neoplasms↗
PubMed1997

N-Myc gene amplification is a major prognostic factor in localized neuroblastoma: results of the French NBL 90 study. Neuroblastoma Study Group of the Société Francaise d'Oncologie Pédiatrique.

PURPOSE: To assess the relevance of N-Myc gene amplification (NMA) as a prognostic factor in localized neuroblastoma (NB) and to evaluate whether less intensive adjuvant treatment is advisable in infants without NMA. PATIENTS AND METHODS: Assessment of NBs included clinical and imaging data to allow tumor-node-metastasis (TNM) staging, biologic determinations (N-Myc gene analysis), and standard histology and work-up to eliminate metastatic spread (metaiodobenzylguanidine [MIBG] scintigraphy and extensive bone marrow staging). Resectability was defined according to imaging findings. Chemotherapy was indicated in children older than 1 year at diagnosis who had postoperative residual disease or lymph node (LN) involvement, in infants with NMA, or as primary treatment in children with an unresectable NB, including dumbbell tumors. Radiotherapy was recommended in children older than 1 who presented with persistent gross residual disease at the end of therapy. RESULTS: Between 1990 and 1994, 316 consecutive children who presented with a localized NB were registered in the NBL 90 study. The median age was 12 months, and 42 patients had dumbbell tumors (13%). NMA was found in 22 of 225 assessable children (10%) and correlated with adverse prognostic indicators such as age older than 1 year, an abdominal primary tumor, a large tumor (T3), and unresectability. Among 186 children who had primary excision, five died of surgery-related complications. Primary chemotherapy was given to 130 patients, which allowed removal of the tumor in all but four. The 5-year overall survival (OS) and event-free survival (EFS) rates were, respectively, 91% and 84% with a median follow-up time of 36 months. The outcome of infants and older children was similar (P = .2). EFS of patients with resectable tumors was slightly better than with unresectable primary tumors (EFS, 89% v 78%; P = .02). In dumbbell NBs, neurologic recovery was achieved in 74% of cases that presented with symptoms, and initial laminectomy was avoided in 75% of children. In a univariate analysis, large tumors, high neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, positive LNs, macroscopic residue, and NMA adversely influenced outcome. In the multivariate analysis, NMA was the most powerful unfavorable predictive indicator: OS and EFS rates for these children were 36% and 32%, compared with 98% and 90% in nonamplified tumors (P < .001). CONCLUSION: Our data confirm the overall good prognosis of localized NBs, even when unresectable. NMA is the most relevant adverse prognostic factor in localized NBs, and more intensive treatment should be investigated in these patients. Prospective studies of other biologic factors are warranted to tailor therapy more accurately. The EFS of children who underwent primary surgery was excellent, and further justifies elimination of adjuvant treatment provided they have no NMA. Despite the elimination of postoperative therapy, infants with non-NMA tumors have an excellent outcome, which suggests that initial chemotherapy can be further reduced in case of unresectable NBs.

Adolescent↗
PubMed1997

[Extra-cardiac rhabdomyoma of the fetal type].

Rhabdomyomas are benign tumors of striated muscle. They are distinguished by topographic data: cardiac or genital and by histological criteria: foetal or adult type. The foetal type is the most heterogeneous, with either a majority of immature cells or a mixture of maturing elements. This diversity has led to distinguish immature (or standard) foetal Rhabdomyomas from intermediate foetal Rhabdomyomas. One observation of this last type is reported. The authors highlight the essential characteristics of foetal Rhabdomyomas, however the exact meaning remains unclear: an anomaly in the differentiation of the striated muscle? or a true tumoral process through genetic anomaly?

Fetal Diseases↗
PubMed1996

The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients--results of the NBL 90 Study of the French Society of Pediatric Oncology.

BACKGROUND: Neuroblastoma is the most common malignant cause of spinal compression in the pediatric population. More than 30% of patients who are impaired prior to treatment remain impaired after the completion of therapy. Those who do not improve after decompressive laminectomy may go on to develop severe delayed spinal deformities. METHODS: To decrease the long term sequelae of routine neurosurgical intervention for all intraspinal extensions of neuroblastoma, the French NBL 90 Study was formulated to use chemotherapy as a first-line treatment for all nonmetastatic neuroblastomas with intraspinal extension. Neurosurgical decompression and excision was recommended only for patients demonstrating rapid neurologic deterioration. RESULTS: The overall survival of the 42 patients registered was 97%. Initial neurologic impairment was present in 27 patients (64%), including 11 with paraplegia. Thirty-two patients received chemotherapy as first-line treatment. Complete regression of the intraspinal component was observed in 13 patients and partial regression of greater than 50% of the initial volume in 5 patients. Of 19 evaluable patients presenting with a neurologic deficit and treated with primary chemotherapy, recovery was completed in 11 and partial in 3. Four patients failed to recover from long-standing pretreatment paraplegia. Only one patient worsened during therapy, and recovered completely after emergent neurosurgical intervention. Seven patients underwent initial neurosurgical procedures; six had a neurologic deficit and five recovered completely, including all three who presented with acute onset of paraplegia. Three patients had extraspinal surgery as exclusive treatment. Six patients (15%) suffered severe neurologic sequelae. Only one of the patients who underwent surgery required spinal stabilization for progressive deformity, but follow-up is limited. CONCLUSIONS: By treating patients with dumbbell neuroblastoma initially with chemotherapy, the authors were able to reduce the size of the intraspinal mass in 58% of patients, improve partial neurologic deficits in 92%, and avoid neurosurgical decompression in 60%. Neurologic deficits also improved in 83% of patients requiring emergent neurosurgical intervention.

Adolescent↗
PubMed1996

Lack of intermediate-affinity interleukin-2 receptor in mice leads to dependence on interleukin-2 receptor alpha, beta and gamma chain expression for T cell growth.

An interleukin (IL)-4 dependent mouse T cell clone 8.2 derived from an IL-2-dependent T cell line was characterized. As measured by flow cytometric analysis and Northern blotting, it expresses IL-2 receptor beta (IL-2R beta) and gamma (IL-2R gamma) chains, but has lost expression of IL-2 receptor alpha chain (IL-2R alpha). To investigate the properties of the mouse IL-2R beta gamma complex and the role of IL-2R alpha gene expression, this clone was further studied. T cell clone 8.2 has lost the capacity to bind 125I-labeled human IL-2 under experimental conditions able to detect intermediate-affinity IL-2R in human cells. Mouse IL-2 is unable to block the binding of mAb TM beta 1 to 8.2 cells. Under the same experimental conditions, mouse IL-2 blocks the binding of TM beta 1 to C30-1 cells expressing the IL-2 alpha beta gamma complex. Since TM beta 1 recognizes an epitope related to the IL-2 binding site of IL-2R beta, these results can be taken as a demonstration that mouse IL-2R beta gamma does not bind mouse IL-2. Furthermore, T cell clone 8.2 does not proliferate in response to recombinant mouse or human IL-2. On the other hand, T cell transfectant lines expressing heterospecific receptors made of the human IL-2R beta and mouse IL-2R gamma chains bind 125I-labeled human IL-2 and proliferate in response to IL-2. This establishes the difference between mouse and human IL-2R beta chains. Transfection of T cell clone 8.2 with human IL-2R alpha genes restores their capacity to proliferate in response to IL-2. In addition, all transfectants grown in IL-2 express the endogeneous mouse IL-2R alpha chain. When grown in IL-4, the endogeneous mouse IL-2R alpha gene remains silent in all these transfectants. These results show that, contrary to the human, the mouse does not express an intermediate-affinity IL-2R. Expression of the IL-2R alpha gene is therefore required for the formation of the functional IL-2R in mice.

Animals↗
PubMed1996

Ligand-induced autoregulation of IL-2 receptor alpha chain expression in murine T cell lines.

The IL-2 receptor (IL-2R) is composed of three chains alpha, beta and gamma. In mice, contrary to the human system, we have previously demonstrated that the IL-2R beta gamma complex does not bind IL-2. Therefore, mouse IL-2 response is completely dependent on the expression of the IL-2R alpha gene product. T cell clones expressing mouse IL-2R beta gamma and the human IL-2R alpha transgene have been studied. When cells are grown in IL-4, mouse IL-2R alpha is not expressed. However, exposure to IL-2 leads to the expression of the endogenous murine IL-2R alpha subunit. The T cell line expressing mouse IL-2R gamma and human IL-2R beta can grow in IL-2 but does not express endogenous murine IL-2R alpha. Transfection of these cells with the human IL-2R alpha gene restores the capacity to induce murine IL-2R alpha. This result demonstrates that IL-2-IL-2R alpha interactions are required for induction of IL-2R alpha. The kinetics of induction and deinduction of murine IL-2R alpha have been studied using clone 18.III. From negative cells, expression of murine IL-2R alpha is a very slow phenomenon. From cells fully expressing IL-2R alpha, deinduction is a two-step process: after a rapid decrease of IL-2R alpha the cells continue to express, for a long period of time, basal levels of murine IL-2R alpha. When cells expressing basal levels of IL-2R alpha are exposed to IL-2, induction of IL-2R alpha is a very rapid phenomenon. The autoregulatory loop formed by IL-2-IL-2R alpha therefore displays different levels of functioning.

Animals↗
PubMed1996

Giant cell tumor of bone in children and adolescents.

Giant cell tumor of bone rarely affects children, in whom it is usually located in a metaphysis in contrast to the predominantly epiphyseal localization in adults. Five cases are reported, two at the femur, two at the fibula and one at the tibia. Plain film radiography and computed tomography are the most informative imaging studies. The differential diagnosis is with aneurysmal bone cyst and, in metaphyseal-epiphyseal forms, with chondroblastoma. Treatment usually consists in curettage of the tumor followed by filling of the cavity; however, more extensive resection is required in some cases.

Adolescent↗
PubMed1995

Control of the IL-2 responsiveness of B lymphocytes by IL-2 and IL-4.

A two-step culture system was used to analyze the parameters involved in the acquisition of IL-2 responsiveness by murine B cells. In the first culture, unstimulated, or resting, B cells prepared from spleen of naive animals were challenged during 48 h with IL-2, IL-4, anti-mu, anti-mu+IL-2, anti-mu+IL4, or anti-mu+IL-2 + IL-4. In a second culture, IL-2 responsiveness was followed by measuring either the cell proliferation or the Ig production. It was found that only B cells stimulated by anti-mu+IL-2 were able to respond. The expression of three chains of the IL-2 receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma) was studied by FACS. IL-2R beta and IL-2R gamma were found to be expressed constitutively on resting B cells. IL-2R alpha was induced by anti-mu and anti-mu+IL-2 treatment. Although B cells treated by anti-mu alone are not able to respond to IL-2, they do express an IL-2 binding capacity comparable with B cells treated by anti-mu+IL-2. This paradoxical result suggests that IL-2 has a direct influence on the acquisition of the IL-2 responsiveness. IL-4 exerts a negative effect on the IL-2 response. At the molecular level, IL-4 was found to reduce selectively the IL-2R beta expression at the B cell surface. This effect was confirmed by Northern blot analysis. Maximum expression of the IL-2R beta mRNA is obtained after anti-mu+IL-2 treatment. In the presence of IL-4, expression of the IL-2R beta mRNA is greatly reduced.

Animals↗
PubMed1995

[Favorable outcome of orbital nasal sinus mucormycosis complicating the induction treatment of acute lymphoblastic leukemia].

BACKGROUND: Most cases of mucormycosis occur in immunosuppressed children. Intracranial extension is lethal and must be prevented with early specific treatment. CASE REPORT: A 42 month-old boy was admitted suffering from acute lymphoblastic leukemia. Edema of the left eyelid developed on the sixth day of induction chemotherapy. Mucormycosis was suspected because of gradual extension of infection to nasal ala and periorbital area with fever, edema of nasal turbinates and nasal black secretions. Chemotherapy was discontinued and the patient was given intravenous amphotericin B (1.0 mg/kg/day) and heparin associated with G.CSF. Improvement was only temporary and scan examination performed on day 17 showed involvement of the orbit, eye and wall of the maxillary sinus; cultures of secretions were positive for staphylococcus and Absidia corymbifera. Remission of leukemia was obtained a few days later permitting surgical resection of involved tissues on day 30. A relapse of mucormycosis was observed six weeks later despite prolonged administration of amphotericin B requiring extended resection of necrotic areas and replacement of amphotericin B by its liposomal form (Ambisome). Bone marrow relapse of leukemia required further chemotherapy. The patient is in good condition 30 months after the initial symptoms. CONCLUSION: Our patient seems to be the first with prolonged remission of facial mucormycosis and acute leukemia despite relapse of both diseases. This favorable outcome could be due to the use of Ambisome.

Amphotericin B↗
PubMed1994

Human lupus anti-DNA autoantibodies undergo essentially primary V kappa gene rearrangements.

We have recently characterized the heavy chain variable region (VH) genes expressed by a panel of human anti-DNA antibodies derived from four patients with systemic lupus erythematosus and expressing an idiotypic marker representative of a subset of pathogenic autoantibodies. Here, we have cloned and sequenced the kappa chain variable region genes (V kappa) of the clones whose VH genes had been previously analysed. All the V kappa genes utilized map to the 280 kb portion of the 3' end of the locus, suggesting that they represent essentially the products of primary rearrangements. This proximal clustering of the V kappa genes used contrasts with the broad distribution of immunization-induced human antibody V kappa genes over 1400 kb of the locus. In addition, lupus autoantibodies show no tendency to express the downstream junctional (J kappa) exons--another indication of infrequent secondary variable gene assembly. Since successive rearrangements may extinguish high-affinity recognition of self antigens, we propose that this bias in V kappa and J kappa expression reflects a low rate of secondary light chain rearrangements among lupus autoantibodies. We also postulate that the corrective mechanism capable of editing potentially aggressive, self-reactive antibodies in these patients may be deficient--a deficit that could be genetically determined and/or somatically acquired.

Amino Acid Sequence↗
PubMed1994

Somatic diversification in the heavy chain variable region genes expressed by human autoantibodies bearing a lupus-associated nephritogenic anti-DNA idiotype.

Monoclonal anti-DNA antibodies bearing a lupus nephritis-associated idiotype were derived from five patients with systemic lupus erythematosus (SLE). Genes encoding their heavy (H)-chain variable (VH) regions were cloned and sequenced. When compared with their closest VH germ-line gene relatives, these sequences exhibit a number of silent (S) and replacement (R) substitutions. The ratios of R/S mutations were much higher in the complementarity-determining regions (CDRs) of the antibodies than in the framework regions. Molecular amplification of genomic VH genes and Southern hybridization with somatic CDR2-specific oligonucleotide probes showed that the configuration of the VH genes corresponding to VH sequences in the nephritogenic antibodies is not present in the patient's own germ-line DNA, implying that the B-cell clones underwent somatic mutation in vivo. These findings, together with the characteristics of the diversity and junctional gene elements utilized to form the antibody, indicate that these autoantibodies have been driven through somatic selection processes reminiscent of those that govern antibody responses triggered by exogenous stimuli.

Amino Acid Sequence↗
PubMed1994

Carboplatin and VP 16 in medulloblastoma: a phase II Study of the French Society of Pediatric Oncology (SFOP).

The purpose of this study is to evaluate the antitumor activity of combination carboplatin and etoposide in measurable medulloblastoma. From January '89 to January '92, 26 patients with medulloblastoma were included in a multicentric phase II study of 2 courses of carboplatin 160 mg/m2/d day 1 to day 5 and VP16 100 mg/m2/d day 1 to day 5. Median age was 10 years (19 months-14.5 years). First treatment was surgery alone in 1 patient, surgery + radiotherapy in 4 patients, surgery + chemotherapy in 2 patients less than 3 years old, surgery + radiotherapy + chemotherapy in 19 patients ("8 drugs in 1 day" based:17, SIOP I:1, SIOP II:1). Previous treatment included cisplatin (20 cases), carboplatin (1 case), and VP16 (7 cases). Measurable disease was evaluated by CT scan, MRI or myelogram and CSF. Response rate (RR) was 72 +/- 10%:8 complete responses (CR), 10 partial responses (PR), 1 objective effect (OE), 6 progressive disease (PD), 1 non-evaluable. Thirty-six courses were evaluated for toxicity. Median duration of WHO grade 4 neutropenia was 8 days (0-23). One patient died at day 18 after the first course because of diffuse haemorrhage during septic aplasia. Five other non-life-threatening septicemias were recorded. Median number of platelet transfusions was 1 (0-4). One child who had achieved a PR after two courses died from CNS bleeding after the third course. This drug combination achieves a high response rate in childhood medulloblastoma. Severe toxicity has been mainly encountered in previously heavily treated patients. Tolerance may be acceptable in newly diagnosed children, but careful hematological follow-up and platelet transfusional support are definitely mandatory.

Adolescent↗
PubMed1994

Clonotypic dominance and variable gene elements of pathogenic anti-DNA autoantibodies from a single patient with lupus.

This study explores the usage and diversity of the variable gene elements expressed by human lupus antibodies to DNA bearing the 0-81 idiotype, a marker of pathogenic anti-DNA autoantibodies. Rather than studying DNA-specific clonotypes from different patients, a panel of idiotype positive anti-DNA autoantibody-secreting clones from a single individual were analysed. By cloning and nucleotide-sequencing the heavy-chain variable gene segments, evidence was found for dominance of clonotypic patterns. Also noted was a high rate of diversification among the variable (VH), diversity (DH) and junctional (JH) gene segments utilized, with a pattern of mutations indicative of antigenic selection. These features suggest that the clones secreting the lupus pathogenic autoantibodies have been selected over multiple generations through an affinity-maturation process that is reminiscent of antigen-driven immune responses.

Adult↗
PubMed1994

[Papilloma of the choroid plexus. Apropos of 11 cases].

The authors report 11 cases of choroid plexus papillomas in children operated on from 1979 until 1993. The age ranges from 2 months to 14 years old. The most frequent location occurred in the lateral ventricles (7 cases) followed by the locations in the third ventricle (3 cases) and the fourth ventricle (1 case). A complete resection was performed in all the cases. Hydrocephalus induced by the tumors was always present. An internal and permanent shunting procedure was carried out in the pre-operative period in 5 cases, in the post-operative course in 1 case. 3 cases underwent an external CSF shunting before surgery. This external CSF drainage has been taken out a few days after the surgical resection and no further permanent internal shunting was required in the long-term outcome. In 2 cases, no CSF drainage was performed either before or after surgery. Choroid plexus papillomas (CPP) require surgical management. The hypervascularisation of these tumors can give rise to important bleeding and generate surgical difficulties particularly in children under one year. The best way to remove these tumors would be to reach the arterial feeder(s) in first place, but it is not always possible. It's also difficult to forecast wether or nor the hydrocephalus will require further permanent CSF drainage, so we have chosen to carry on an external and transient CSF shunting.

Adolescent↗
PubMed1993

Phase II study of ifosfamide in childhood brain tumors: a report by the French Society of Pediatric Oncology (SFOP).

Forty-two evaluable pediatric patients with a variety of recurrent primary brain tumors participated in a phase II ifosfamide trial. Their mean age was 10 years. All patients were treated with ifosfamide, 3 g/m2/day for 2 days every 2 weeks. Response was assessed on clinical and radiological criteria after at least 2 courses of therapy. The overall response rate was 12% (5/42). One complete and 2 partial responses were documented in 21 patients with medulloblastoma. A partial response was demonstrated in 1 patient with primitive neurectodermal tumor (PNET) and in 1 patient with ependymoma. No activity was observed in astrocytic tumors. Toxicity was primarily neurologic (16 out of 54 patients, 30%). Hematological toxicity, without severe morbidity, was encountered in 9% of courses (16/179). Ifosfamide, administered at this dose regimen has modest efficacy in the treatment of recurrent childhood medulloblastoma and ependymoma and appears inactive for gliomas. Further trials with other dose schedules are necessary to assess the activity of this drug. However, according to the neurotoxicity observed in our trial, we would not recommend building a protocol using ifosfamide for highly progressive brain tumors.

Adolescent↗