Proton beam therapy in the management of central nervous system tumors in childhood: the preliminary experience of the Centre de Protonthérapie d'Orsay

BACKGROUND: The purpose of the study was to evaluate clinical results and complications of a combination of proton and photon irradiation administered to 17 children with selected central nervous system (CNS) tumors. PROCEDURE: Between July 1994 and September 2000, 17 children, aged from 5 to 17 years (median: 12 years) with intracranial benign (6 cases) or malignant (11 cases) tumors, were treated with photons (median dose: 40 Gy; 24-54) and protons (median dose: 20 CGE; 9-31) at the Centre de Protonthérapie d'Orsay (CPO). RESULTS: Mean follow-up was 27 months (3-81). Two patients recurred locally (one marginal and one in situ). Fifteen patients are alive and doing well. Overall, 12, 24, and 36-month local control rate was 92 +/- 8% and, 12, 24, and 36-month overall survival rates were 93 +/- 6%, 83 +/- 11%, and 83 +/- 11%, respectively. Clinical initial symptoms remained stable or subsided in all patients. Early toxicities were in the expected range. CONCLUSIONS: With a mean 27 months follow-up, protontherapy was well tolerated for doses upto 69 CGE and with an excellent local control rate.     

The combined analysis of P-glycoprotein expression and activity predicts outcome in childhood acute lymphoblastic leukemia

The link between drug resistance and relapse was often suggested, but rarely demonstrated in long-range clinical studies. Since it is nowadays recommended to validate immunocytochemical results, the authors studied prospectively 52 acute lymphoblastic leukemia (ALL) patients with an immunocytochemical test and a functional flow cytometric test. The 4-year EFS and OS were 79.3% and 85.2%, respectively. Patients scoring positive in both tests had a significantly higher relapse rate and worse survival (log rank p = .007 and .047 for event-free survival and overall survival, respectively). Among the different prognostic variables evaluated, only the combination of P-gp expression and activity was a statistically significant parameter predicting relapse in childhood ALL.     

PARC/CCL18 is a plasma CC chemokine with increased levels in childhood acute lymphoblastic leukemia

Chemokines play an important role in leukocyte mobilization, hematopoiesis, and angiogenesis. Tissue-specific expression of particular chemokines also influences tumor growth and metastasis. Here, the CC chemokine pulmonary and activation-regulated chemokine (PARC)/CCL18 was measured in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Surprisingly, PARC immunoreactivity was consistently detected in plasma from healthy donors. After purification to homogeneity, the presence of intact PARC (1-69) and processed PARC (1-68) in normal human plasma was confirmed by sequence and mass spectrometry analysis. Furthermore, PARC serum levels were significantly increased in children with T-ALL and prepreB-ALL compared to control serum samples, whereas serum levels in AML and preB-ALL patients were not significantly different from controls. In contrast, the hemofiltrate CC chemokine-1 (HCC-1)/CCL14 was not found to be a biomarker in any of these patients' strata, whereas the cytokine interleukin-6 (IL-6) was significantly decreased in AML and prepreB-ALL. Stimulated leukocytic cell lines or lymphoblasts from patients produced IL-8/CXCL8 or macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3) but not PARC, not even after IL-4 or IL-10 treatment. However, PARC was produced by superantigen or IL-4 stimulated monocytes co-cultured with lymphocytes or lymphoblastic cells. Serum PARC levels thus constitute a novel leukemia marker, possibly reflecting tumor/host cell interactions in the circulation.     

Long-term results after neovagina creation in Mayer-Rokitanski-Kuster-Hauser syndrome by Vecchietti's operation

OBJECTIVES: To evaluate the long-term results after Vecchietti's operation. STUDY DESIGN: Twenty Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome patients underwent creation of a neovagina using Vecchietti's operation by laparotomy (17 cases) and laparoscopy (3 cases). RESULTS: The mean age of the patients was 21 years (16-34). After 66 months (24-156) of follow-up, the mean length x diameter of the neovagina was 8.2 cm x 2.8 cm. The neovaginal epithelium was macroscopically similar to normal vaginal mucosa, except for one patient who had subsequently undergone insertion of skin graft. Post-operative sexual behavior revealed sexual desire and pleasure (100%), lubrication (94%), clitoral orgasm (87%) and vaginal-mediated orgasm (69%). Finally, 16 patients out of 18 (89%) were completely satisfied with the results of the operation. CONCLUSION: Vecchietti's operation may be suggested as one of the choice of treatments to correct vaginal aplasia in young MRKH syndrome patients.     

Rapid detection of common autosomal aneuploidies by quantitative fluorescent PCR on uncultured amniocytes

Prenatal diagnosis of chromosomal abnormalities by cytogenetic analysis is time consuming, expensive, and requires highly qualified technicians. Rapid diagnosis of aneuploidies followed by reassurance for women with normal results can be performed by molecular analysis of uncultured foetal cells in less than 24 h. Today, all molecular techniques developed for a fast diagnosis of aneuploidies rely on the semi-quantification of fluorescent PCR products from short tandem repeat (STR) polymorphic markers. Our objective was to test a chromosome quantification method based on the analysis of fluorescent PCR products derived from non-polymorphic target genes. An easy to set up co-amplification of portions of DSCR1 (Down Syndrome Critical Region 1), DCC (Deleted in Colorectal Carcinoma), and RB1 (Retinoblastoma 1) allowed the molecular detection of aneuploidies for chromosomes 21, 18 and 13 respectively. Quantitative analysis was performed in a blind prospective study of 400 amniotic fluids. Four samples (1%) could not be analysed by PCR probably because of a low concentration of foetal DNA. Follow up karyotype analysis was done on all samples and molecular results were in agreement with the cytogenetic data with no false-positive or false-negative results. Our gene based fluorescent PCR approach is an alternative molecular method for a rapid and reliable detection of aneuploidies which can be helpful for the clinical management of high-risk pregnancies.     

Analysis of undetectable HIV RNA using survival analysis: results must be interpreted carefully

This methodological note exemplifies the drawbacks of conventional survival analysis for studying the determinants of the evolution of HIV RNA after the initiation of a HAART regimen in observational cohort studies. The potential for loss of information might yield differential misclassification biases and therefore unreliable results. Longitudinal models are better suited to analyze the repeated measures of a continuous outcome such as HIV RNA.     

Effects of estradiol,phytoestrogens, and Ginkgo biloba extracts against 1-methyl-4-phenyl-pyridine-induced oxidative stress

Oxidative stress has been recently considered as a mediator of nerve cell death in several neurodegenerative diseases. We studied the effect of the parkinsonism-inducing toxine 1-methyl-4-phenyl-pyridine (MPP+) on several parameters of cell distress using native and neuronal PC12 cells. Then, since estrogens have been reported to prevent neuronal degeneration caused by oxidative damage, we investigated the ability of 17beta- estradiol (E2); two Ginkgo biloba extracts, EGb 761 and Cp 202; as well as two flavonoids, quercetin and kaempferol, to rescue PC12 cells submitted to MPP+- induced oxidative stress. Our results consistently show that both Ginkgo biloba extracts could prevent cell death in native and neuronal PC12 cells, while in neuronal PC12 cells also quercetin and E2 could reverse MPP+ neurotoxic effet. Western blot analysis demonstrated that MPP+ injuries might modulate dopamine transporter (DAT) protein expression but not estrogen receptor beta (ERbeta) protein expression. EGb 761 and Cp 202 also modulate DAT and ERbeta protein expression in neuronal cells. From these studies, we outline the importance of testing estrogen-like plant-derived molecules as potent antioxidants and examine their effect on protein expression.