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Philippe Colin

Publications and source records attributed to Philippe Colin.

10 recordsLinked to original sources
PubMed2006

1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase.

Oxidative stress has been suggested to be an important mediator of dopaminergic cell death in Parkinson's disease (PD). We investigated the neuroprotective potential of Cu/Zn superoxide dismutase (SOD1) overexpression in the rat substantia nigra (SN) following adenovirus-mediated gene transfer. Human dopaminergic SK-N-SH cells were transduced with adenoviral vectors expressing either human SOD1 (Ad-SOD1) or beta-galactosidase (Ad-betagal) before exposure to 1 mM of the 1-methyl-4-phenylpyridinium ion (MPP+). A strong neuroprotective effect of SOD1 gene transfer was observed in the SK-N-SH cells exposed to MPP+ compared with controls. Adult rats were then given unilateral injections of either Ad-SOD1 or Ad-betagal into the striatum, and MPP+ was administered 8 days later at the same location. Strong transgene expression was detected in the SN dopaminergic neurons, a consequence of retrograde axonal transport of the adenoviral particles. The amphetamine-induced rotational behavior of the rats was markedly lower in Ad-SOD1-injected rats than in control animals. Also, behavioral recovery significantly correlated with the number of tyrosine hydrolase-expressing neurons in the SN of the treated rats. These results are consistent with oxidative stress contributing to the MPP+ -induced neurodegenerative process. They also indicate that SOD1 gene transfer into the nigrostriatal system may be a potential neuroprotective strategy for treating PD.

1-Methyl-4-phenylpyridinium↗
PubMed2006

Colon cancer.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed2005

Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients.

PURPOSE: To optimize and reduce the toxicity of pituitary adenoma irradiation by assessing the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR). METHODS AND MATERIALS: Between 1990 and 1999, 110 consecutive patients, 47 with a functioning adenoma, were treated according to a strategy of either early surgery and FSR (n = 89) or FSR only (n = 21). Of the 110 patients, 75 had persistent macroscopic tumor and 47 persistent hormonal secretions; 15 were treated in the prophylactic setting. The linear accelerator-delivered dose was 50.4 Gy (5 x 1.8 Gy weekly), with a 2-mm safety margin. RESULTS: After a minimal follow-up of 48 months, only 1 patient had developed progression. Of the 110 patients, 27 (36%) had a complete tumor response, 67 (89.3%) had an objective tumor response, 20 (42%) had a hormonal complete response, and 47 (100%) had a hormonal objective tumor response. The proportion of patients without a complete tumor response, objective tumor response, complete hormonal response, and objective hormonal response was 85.1%, 62%, 83%, and 59.3% at 4 years and 49.3%, 9%, 59.3%, and 10.6% at 8 years, respectively. The sole unfavorable predictive factor was preoperative SSE >20 mm for tumor response (p = 0.01) and growth hormone adenoma for the hormonal response (p <0.001). No late complications, except for pituitary deficiency, were reported, with a probability of requiring hormonal replacement of 28.5% and 35% at 4 and 8 years, respectively. Nonfunctioning status was the sole unfavorable factor (p = 0.0016). CONCLUSIONS: Surgery plus FSR is safe and effective. FSR focused to the target volume seems more suitable than standard radiotherapy, and standard fractionation reduces the risk of optic neuropathy sometimes observed after single-dose radiosurgery. Therefore, FSR allows us to consider combined transrhinoseptal surgery and early radiotherapy, with a curative goal without patient selection.

Adenoma↗
PubMed2003

FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.

PURPOSE: In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B). PATIENTS AND METHODS: Previously untreated patients with assessable disease were randomly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2) or dl-LV 400 mg/m(2) followed by a FU bolus 400 mg/m(2) and 46-hour infusion 2,400 to 3,000 mg/m(2) every 46 hours every 2 weeks, either with irinotecan 180 mg/m(2) or with oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 1. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B). RESULT: Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI (P =.99). Median second progression-free survival (PFS) was 14.2 months in arm A versus 10.9 in arm B (P =.64). In first-line therapy, FOLFIRI achieved 56% response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54% RR and 8.0 months median PFS (P =.26). Second-line FOLFIRI achieved 4% RR and 2.5 months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI, and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6. CONCLUSION: Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.

Adult↗
PubMed2003

Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial.

PURPOSE: This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer. PATIENTS AND METHODS: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion. RESULTS: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001). CONCLUSION: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.

Adenocarcinoma↗
PubMed2003

Transforming growth factor beta1 overexpression in the nigrostriatal system increases the dopaminergic deficit of MPTP mice.

Idiopathic Parkinson's disease (PD) is characterized by mesencephalic dopaminergic neuron cell death and striatal dopamine (DA) depletion. The factors involved in the pathogenesis of the disease are still unknown. Transforming growth factor beta1 (TGFbeta1) is increased in the striatum of patients with PD. However, the effect of this increase is not known. Here, we show that overexpression of TGFbeta1, by recombinant adenovirus TGFbeta1 gene transfer, in the mesostriatal system of an MPTP mouse model of PD decreased the number of mesencephalic dopaminergic neurons. This effect also involved more extensive DA depletion in the striatum. Striatal enkephalin mRNA levels are augmented, suggesting a decrease in dopaminergic transmission to the postsynaptic target. In the absence of MPTP, TGFbeta1 greatly decreased the number of dopaminergic neurons in the ventral mesencephalon of fully mature mice. These results show that an increase in TGFbeta1 levels aggravate the parkinsonian status of MPTP mice and may therefore be a risk factor for the development of PD.

Animals↗
PubMed2003

Targeting conditional gene modification into the serotonin neurons of the dorsal raphe nucleus by viral delivery of the Cre recombinase.

Delivery of viral vectors encoding the Cre recombinase is showing promise to target gene modification in specific brain regions. Here we describe the targeting of the dorsal raphe nucleus (DRN), which contains the majority of the serotonin (5-HT) neurons projecting to the forebrain. First, we demonstrate successful transgene expression in the mouse DRN by stereotaxic delivery of the AdnlslacZ adenoviral vector. Second, we show that expression of the Cre recombinase can be achieved in the 5-HT neurons by optimized injection of the Adcre vector. Using reporter mice in which Cre activity induces beta-galactosidase (beta-gal) expression, we demonstrate efficient Cre-mediated recombination and persistence of beta-gal positive 5-HT neurons at least 1 month postinjection. Together, these results demonstrate that viral delivery provides a valuable method to target Cre recombination throughout the murine DRN and thus to study 5-HT neurotransmission by conditional gene modification.

Adenoviridae↗
PubMed2002

Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial.

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.

Adolescent↗