Intérêt de l anticorps Immunoglobulines G Anti Hsp70.1 dans le diagnostic de toxoplasmose oculaire

La toxoplasmose oculaire est la première cause d uvéite postérieure, dont le retentissement peut conduire à la cécité. L objectif de cette étude était d améliorer le diagnostic des formes atypiques de toxoplasmose oculaire (TO) grâce au dosage sérique d un nouveau marqueur l anticorps Immunoglobulines G Anti Hsp70.1 (Ac IgG Anti Hsp70.1). Cette étude prospective et multicentrique a inclus 21 patients atteints de TO confirmés par la biologie, 30 patients suspects de toxoplasmose présentant une choriorétinite et 42 patients témoins (atteints de cataracte). La confirmation biologique faisait appel au coefficient de Goldmann-Witmer, Western Blot ou la PCR. Les taux d anticorps ont été déterminés par méthode ELISA. La valeur sérique de l Ac IgG anti Hsp70.1 était significativement différente selon la zone de rétine atteinte (p=0.006) ainsi qu en fonction de la taille de la lésion choriorétinienne (p=0.03). La détermination par la méthode de la courbe ROC d un seuil de l Ac IgG anti Hsp70.1 à partir des valeurs des Anticorps anti toxoplasmose dans l humeur aqueuse n a pas montré de différence entre nos 3 groupes (p=0.57). Dans le groupe suspect de toxoplasmose, la mesure de l Ac IgG anti Hsp70.1 a permis de confirmer biologiquement 10 patients sur 18 présentant une TO clinique. En conclusion, l Ac IgG Anti Hsp 70.1 peut être utilisé, en complément des autres méthodes biologiques, pour confirmer l étiologie toxoplasmique d une choriorétinite. Une étude complémentaire de son dosage dans l humeur aqueuse devrait permettre de mieux appréhender la relation entre l Ac IgG Anti Hsp 70.1 et le diagnostic, ainsi que la sévérité de la toxoplasmose oculaire.Laboratory diagnosis of ocular toxoplasmosis (OT) needs to be improved mainly in clinical atypical cases. In a retrospective previous study, infected patients could display serum IgG anti-Hsp70.1 antibodies and that these antibodies could be used to improve the diagnosis of OT. The purpose of this multicentre prospective case-control study was to correlate clinical features with IgG anti-Hsp70 antibodies. We have included patients with confirmed (Group A1) or suspected OT (Group A2), and with cataract (Control Group B). The diagnosis was based on the ocular presentation, Goldmann-Witmer s coefficient, immunoblotting and/or PCR. Serum and aqueous humour (AH) were sampled at the time of uveitis. ELISA was used to measure serum anti-Hsp70.1-antibody levels. The OT patients were clinically followed up to six months and laboratory monitored up to three months. Serum IgG anti-Hsp70.1 antibody levels were related to the affected retinal zone (p=0.006) and were correlated significantly to the retinal lesion size (p<0.05). Serum anti-Hsp70.1 and AH IgG anti-Toxoplasma antibodies were respectively positive in 10 and 5 out of 18 cases of Group A2 that were finally classified as true-clinically suspected OT. Anti-Hsp70 may be involved directly or indirectly in the retinal lesions during ocular Toxoplasma infection and related to the affected retinal zone. Anti-Hsp70.1 antibody may confirm biologically suspected OT with an increasing specificity when associated with the presence of AH IgG anti-Toxoplasma antibodies. The value of AH anti-Hsp-70 antibody levels in the laboratory diagnosis of OT will further evaluated.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial

International audienceBACKGROUND:The primary aim of this trial was to determine the recommended phase II dose (RP2D) of weekly paclitaxel (wP) administered in combination with oral metronomic cyclophosphamide (OMC).METHODS:Patients ≥ 18 years of age with refractory metastatic cancers were eligible if no standard curative measures existed. Paclitaxel was administered IV weekly (D1, D8, D15; D1 = D28) in combination with a fixed dose of OMC (50 mg twice a day). A 3 + 3 design was used for dose escalation of wP (40 to 75 mg/m2) followed by an expansion cohort at RP2D. Dose-limiting toxicity (DLT) was defined over the first 28-day cycle as grade ≥ 3 non-hematological or grade 4 hematological toxicity (NCI-CTCAE v4.0) or any toxicity leading to a dose reduction.RESULTS:In total, 28 pts. (18 in dose-escalation phase and 10 in expansion cohort) were included, and 16/18 pts. enrolled in the dose-escalation phase were evaluable for DLT. DLT occurred in 0/3, 1/6 (neuropathy), 0/3 and 2/4 pts. (hematological toxicity) at doses of 40, 60, 70 and 75 mg/m2 of wP, respectively. The RP2D of wP was 70 mg/m2; 1/10 patients in the expansion phase had a hematological DLT. At RP2D (n = 14), the maximal grade of drug-related adverse event was Gr1 in three patients, Gr2 in six patients, Gr3 in one patient and Gr4 in one patient (no AE in three patients). At RP2D, a partial response was observed in one patient with lung adenocarcinoma.CONCLUSION:The combination of OMC and wP resulted in an acceptable safety profile, warranting further clinical evaluation.TRIAL REGISTRATION:TRN: NCT01374620 ; date of registration: 16 June 2011

Additional file 1 of Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial

Table S1. Adverse events (treatment related or not) reported over the entire treatment duration (all patients, N = 28). Table S2. Characteristics and outcome of patient with lung cancer. (DOCX 31 kb

Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers.

INTRODUCTION:Onapristone is a type I progesterone receptor (PR) antagonist, which prevents PR- mediated DNA transcription. Onapristone is active in multiple preclinical models and two prior studies demonstrated promising activity in patients with breast cancer. We conducted a study of extended release (ER) Onapristone to determine a recommended dose and explore the role of transcriptionally-activated PR (APR), detected as an aggregated subnuclear distribution pattern, as a predictive biomarker. METHODS:An open-label, multicenter, randomized, parallel-group, phase 1 study (target n = 60; NCT02052128) included female patients ≥18 years with PRpos tumors. APR analysis was performed on archival tumor tissue. Patients were randomized to five cohorts of extended release (ER) onapristone tablets 10, 20, 30, 40 or 50 mg BID, or immediate release 100 mg QD until progressive disease or intolerability. Primary endpoint was to identify the recommended phase 2 dose. Secondary endpoints included safety, clinical benefit and pharmacokinetics. RESULTS:The phase 1 dose escalation component of the study is complete (n = 52). Tumor diagnosis included: endometrial carcinoma 12; breast cancer 20; ovarian cancer 13; other 7. Median age was 64 (36-84). No dose limiting toxicity was observed with reported liver function test elevation related only to liver metastases. The RP2D was 50 mg ER BID. Median therapy duration was 8 weeks (range 2-44), and 9 patients had clinical benefit ≥24 weeks, including 2 patients with APRpos endometrial carcinoma. CONCLUSION:Clinical benefit with excellent tolerance was seen in heavily pretreated patients with endometrial, ovarian and breast cancer. The data support the development of Onapristone in endometrial endometrioid cancer. Onapristone should also be evaluated in ovarian and breast cancers along with APR immunohistochemistry validation