The Tumor Microenvironment: The Making of a Paradigm

What has been will be again, what has been done will be done again; there is nothing new under the su

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

PLASMA FROM PATIENTS WITH SEVERE LASSA FEVER PROFOUNDLY MODULATES F-MET-LEU-PHE INDUCED SUPEROXIDE GENERATION IN NEUTROPHILS

In the last years, the number of studies performed by wholly independent research groups that confirm the permanent magnetism, first observed in our research lab, for thiol-capped Au nanoparticles (NPs) has rapidly increased. Throughout the years, the initial magnetometry studies have been completed with element-specific magnetization measurements based on, for example, the x-ray magnetic circular dichroism technique that have allowed the identification of gold as the magnetic moment carrier. In the research work here presented, we have focused our efforts in the evaluation of the magnetic behavior and iron impurities content in the synthesized samples by means of superconducting quantum interference device magnetometry and electron paramagnetic resonance spectrometry, respectively. As a result, hysteresis cycles typical of a ferromagnetic material have been measured from nominally iron-free gold NPs protected with thiol, phosphine, and chlorine ligands. It is also observed that for samples containing both, capped gold NPs and highly diluted iron concentrations, the magnetic behavior of the NPs is not affected by the presence of paramagnetic iron impurities. The hysteresis cycles reported for phosphine-chlorine-capped gold NPs confirm that the magnetic behavior is not exclusively for the metal-thiol system.Ministerio de Ciencia e Innovación CSD2007-00010Junta de Andalucía P06-FQM-02254, P09-FQM-455

Clinical Activity and Tolerability of a 14-Day Infusional Ifosfamide Schedule in Soft-Tissue Sarcoma

Background. Soft-tissue sarcomas (STS) are a heterogeneous group of diseases with lack of effective treatments in most cases. Previous data suggest that continuous infusional ifosfamide regimens might improve cytotoxicity and tolerability compared to standard schedules. Methods. We retrospectively report the outcome of 35 patients affected by STS treated with a 14-day infusional ifosfamide regimen (1000 mg/m(2)/day) in our institution. Predictive factors for toxicity were also explored. Results. Median age was 53 years. There were 16 males and 19 females. Classification by histology was dedifferentiated liposarcoma (DDLPS): 22 (62.8%), synovial sarcoma: 7 (20%), myxoid/round-cell liposarcoma: 3 (8.5%), and others: 3 (8.5%). Overall, 7 patients (20%) achieved partial response (PR) and 10 patients (29%) achieved stable disease (SD). DDLPS showed special sensitivity: 5 patients (22.7%) had PR, 7 patients (31.8%) had SD, and disease control rate was 54.5%. Median progression-free survival and overall survival were 4.2 and 11.2 months, respectively. The most common toxicities were fatigue, nausea, and vomiting (all grades: 85.7%, 83%, and 54.3%, resp.). Neither hypoalbuminaemia nor gender was found to predict toxicity, although encephalopathy predominantly affected females. Conclusion. Ifosfamide administered as a 14-day continuous infusion is a safe regimen in STS with notable activity in DDLPS