This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.

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for the Foie-Alcool group of the Association Française pour l'Etude du Foie (AFEF)** Tumor necrosis factor-␣ (TNF-␣) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH. Patients with severe AAH (Maddrey score >32) were randomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) in weeks 0, 2, and 4; or group B receiving a placebo at the same times. All patients received prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacities were monitored over 28 days. After randomization of 36 patients, seven patients from group A and three from group B died within 2 months. The probability of being dead at 2 months was higher (not significant [NS]) in group A (39% ؎ 11%) than in group B (18% ؎ 9%). The study was stopped by the follow-up committee and the sponsor (Assistance Publique-Hôpitaux de Paris). The frequency of severe infections within 2 months was higher in group A than in group B (P < .002). This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils. There were no differences between the two groups in terms of Maddrey scores at any time point. In conclusion, three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections.

TMZ is well tolerated and provides a substantial rate of response in LGOT. Chromosome 1p loss is correlated with radiographic response and could be a helpful marker for guiding therapeutic decision making in LGOT.

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The phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition. Ninety-two patients with primary AML were analyzed for PI3K/Akt constitutive activation. Fifty percent of the patients presented with constitutive PI3K activation (PI3K ؉ ). No difference was observed between PI3K ؉ and PI3K ؊ groups concerning age, sex, white blood cell count, lactate dehydrogenase (LDH) level, bone marrow blast cells, French-American-British (FAB) classification, cytogenetics, RAS or nucleophosmin (NPM) mutations. Slightly more FLT3-ITD was detected in the PI3K ؊ group (P ‫؍‬ .048). The complete remission rate was similar between the 2 groups. With a median follow-up of 26 months, we observed for PI3K ؉ and PI3K ؊ patients, respectively, 56% and 33% overall survival (P ‫؍‬ .001) and 72% and 41% relapse-free IntroductionSeveral recent articles have highlighted that the class IA phosphoinositide 3-kinase/serine-threonine kinase (PI3K)/Akt pathway is activated in acute myelogenous leukemia (AML), both in blast cells and in the immature CD34 ϩ , CD38 Low , and CD123 ϩ population. 1-4 Most PI3K activity in AML is caused by the p110␦ isoform of PI3K, the activity of which can be specifically inhibited by IC87114. 5,6 The mechanisms leading to PI3K activation are unclear and no activating mutation in the PI3KCD gene coding this isoform has been identified. 7 Two studies have suggested that the prognosis of AML patients with an upregulated PI3K/Akt pathway is worst, suggesting that this pathway could constitute a therapeutic target. 2,8 To ascertain this hypothesis, we prospectively studied constitutive PI3K/Akt/ FOXO3A activation in 92 de novo AML patients. Patients, materials, and methods PatientsNinety-two patients with de novo AML treated in the AML-2001 trial from the Groupe Ouest-Est des Leucémies et Autres Maladies du Sang (GOELAMS) were included, after approval by the GOELAMS Institutional Review Board and receipt of signed informed consent in accordance with the Declaration of Helsinki. The patients received cytosine-arabinoside (200 mg/m 2 , days 1-7) and daunorubicin (60 mg/m 2 , days 1-3) or idarubicin (8 mg/m 2 , days 1-5), and a second course (daunorubicin 35 mg/m 2 , days 17-18 or idarubicin 8 mg/m 2 , days 17-18, and cytosine-arabinoside 1 g/m 2 every 12 hours days 17-20) if bone marrow blasts were more than 5% at day 15. All patients in complete remission received low-dose consolidation with daunorubicin (60 mg/m 2 , days 1-2) or idarubicin (12 mg/m 2 , days 1-2), and cytosine-arabinoside (100 mg/m 2 , days 1-7). Patients with HLAidentical siblings underwent allogenic stem cell transplant (up front until 50 years old; after a consolidation and with a reduced intensity conditioning after 51 years old). Other patients received one consolidation (idarubicin 12 mg/m 2 or daunorubicin 60 mg/m 2 , days 1-2 and cytosine-arabinoside 3g/m 2 every 12 hours days 1-4), followed by autologous stem cell transplantation or high-dose chemotherapy in favorable-ri...

BackgroundDespite a typically good response to first-line combination chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor because of acquired chemoresistance. The use of targeted therapies such as trastuzumab may potentially improve outcomes for patients with ovarian cancer. HER2 overexpression/amplification has been reported in ovarian cancer, but the exact percentage of HER2-positive tumors varies widely in the literature. In this study, HER2 gene status was evaluated in a large, multicentric series of 320 patients with advanced ovarian cancer, including 243 patients enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin-based chemotherapy.Methodology/Principal FindingsThe HER2 status of primary tumors and metastases was evaluated by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis of paraffin-embedded tissue on conventional slides. The prognostic impact of HER2 expression was analyzed. HER2 gene was overexpressed and amplified in 6.6% of analyzed tumors. Despite frequent intratumoral heterogeneity, no statistically significant difference was detected between primary tumors and corresponding metastases.Conclusions/SignificanceOur results show that the decision algorithm usually used in breast cancer (IHC as a screening test, with equivocal results confirmed by FISH) is appropriate in ovarian cancer. In contrast to previous series, HER2-positive status did not influence outcome in the present study, possibly due to the fact that patients in our study received paclitaxel/carboplatin-based chemotherapy. This raises the question of whether HER2 status and paclitaxel sensitively are linked.

A b s t r a c tRecent studies suggest that the incidence of primary central nervous system lymphomas (PCNSLs) is increasing. A few decades ago, PCNSLs accounted for only 1% of all primary intracranial neoplasms. Today, however, they represent between 2% and 6% of all primary brain neoplasms and more than 1% of all non-Hodgkin lymphomas. This trend does not seem totally explained by improved diagnostic techniques or by HIV infection. A substantial increase in PCNSLs among immunocompetent patients has been observed.'"* Most PCNSLs are characterized by a diffuse proliferation of large B cells. 7 Follow-up usually shows a rapid local relapse. Systemic dissemination has been described only rarely. The prognosis remains poor even though some long-term survival has been reported. 38The frequency of each histologic subtype is variable from 1 series to another, and little is known about their biologic characteristics. In a previous article, 9 we reported the major features of 51 AIDS-related PCNSLs. In the present study, we reviewed 72 PCNSLs occurring in immunocompetent patients and studied their clinical and morphologic characteristics, immunophenotype (including expression of bcl-2 and p53), and Epstein-Barr virus (EBV) status. We also studied the impact of these different variables on patient survival. Material and Methods PatientsSeventy-two PCNSLs were studied, including 40 in patients who were part of the lymphomes cerebraux primitifs