Modest single-agent activity and generally manageable adverse events were observed in heavily pretreated RCC and NHL patients. Administration Q3Wk was better tolerated than weekly dosing. Targeted ablation of CD70-positive lymphocytes was demonstrated.

Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naive patients. Patients received vadastuximab talirine IV on day 1 (5-60 µg/kg) or on days 1 and 4 (20 µg/kg) of 21-day cycles. A total of 131 patients (median age, 73 years [range, 26-89 years]) had intermediate I-II (48%) or adverse (34%) risk by European LeukemiaNet classification; 50% of patients had underlying myelodysplasia. Two dose-limiting toxicities (grade 2 pulmonary embolism and grade 4 hypocellular marrow) occurred during dose finding. Most adverse events (AEs) were consistent with myelosuppression; nonhematologic AEs included fatigue, nausea, and diarrhea. The 30-day mortality was 8%. At the recommended monotherapy dose of 40 µg/kg, the complete remission + CRi rate was 28% (5 of 18 patients); 50% of patients who responded achieved minimal residual disease negativity. In patients across dose levels who achieved CR or CRi, the median time to full count recovery was 6.4 weeks for neutrophils (≥1000/µL) and 10.6 weeks for platelets (≥100 × 10/L). Vadastuximab talirine demonstrates activity and a tolerable safety profile as a single agent in patients with AML. The recommended monotherapy dose of vadastuximab talirine is 40 µg/kg. This trial was registered at www.clinicaltrials.gov as # NCT01902329.

Aluminum hypophosphite (AP) and aluminum isobutylphosphinate (APBu) were used to flame retard polyamide 6 (PA6). Addition of either AP or APBu resulted in an increased LOI value, UL-94 V-0 rating, and decreased heat release in cone calorimetric tests. However, different chemical structures of two flame retardants caused different flame-retardant effects: APBu endowed PA6 a higher LOI value and better UL-94 result than did AP. Decomposition pathways of AP, APBu, and the corresponding composites were investigated using TGA, TG-IR, Py-GC/MS, and FTIR characterization of the residues. The introduction of AP changed the thermal stability and decomposition behavior of the composites due to the cross-linking reactions occurred, which were proved by rheological analysis and TG-DSC. APBu could not essentially affect the composition of pyrolysis products and decomposition behaviors, but mainly produced phosphorus-containing free radical scavengers in the gaseous phase, which were positive to flame retardation. Finally, the proposed flame-retardant mechanisms of such systems were summarized.

The aim of this study was to determine whether hemorrhage affects the levels of a variety of stress-related proteins and whether changes can be inhibited by drugs reported to provide protection from ischemia and reperfusion injury. Male Swiss Webster mice were subjected to a 40% hemorrhage without resuscitation. Western blot analysis indicated that c-Jun (an AP-1 protein), Kruppel-like factor 6 (KFL6), and inducible nitric oxide synthase (iNOS) were upregulated sequentially in that order. Pretreatment of mice with geldanamycin (GA) 16 h before hemorrhage effectively inhibited the expression of the proteins KLF6 and iNOS, whereas caffeic acid phenethyl ester did not. GA pretreatment increased inducible heat shock protein (HSP) 70 but not HSP90 in both sham and hemorrhagic tissues. The overexpressed inducible HSP70 formed complexes with KLF6 and iNOS. These results suggest that GA may be therapeutically useful for reducing hemorrhage-induced injury when used as a presurgical treatment or when added to resuscitation fluids.

Cytoskeletal disruption and growth arrest consistently occur in space‐flown human acute leukemic T cells (Jurkat). Although the microtubules appear to reorganize during spaceflight, cells remain nonproliferative. To test the hypothesis that spaceflight alters cytoskeletal gene expression and may thus affect cytoskeletal function, we flew Jurkat cells on Space Transportation System (STS) 95 and compared RNA message by cDNA microarray in space‐flown vs. ground controls at 24 h (4,324 genes) and 48 h (>20,000 genes). Messages for 11 cytoskeleton‐related genes, including calponin, dynactin, tropomodulin, keratin 8, two myosins, an ankyrin EST, an actinlike protein, the cytoskeletal linker (plectin), and a centriole‐associated protein (C‐NAP1), were up‐regulated in space‐flown compared with ground control cells; gelsolin precursor was down‐regulated. Up‐regulation of plectin and C‐NAP1 message in both space‐flown cells and vibrated controls is a novel finding and implies their role in vibration damage repair. This first report of cDNA microarray screening of gene expression in space‐flown leukemic T cells also identifies differential expression of genes that regulate growth, metabolism, signal transduction, adhesion, transcription, apoptosis, and tumor suppression. Based on differential expression of cytoskeletal genes, we conclude that centriole‐centriole, membrane‐cytoskeletal, and cytoskeletal filament associations are altered in the orbital phase of spaceflight.