Non-segmented negative-strand RNA viruses, such as measles, ebola and Newcastle disease viruses (NDV), encapsidate viral genomic RNAs into helical nucleocapsids, which serve as the template for viral replication and transcription. Here, the clam-shaped nucleocapsid structure, where the NDV viral genome is sequestered, was determined at 4.8 Å resolution by cryo-electron microscopy. The clam-shaped structure is composed of two single-turn spirals packed in a back-to-back mode. This tightly packed structure functions as a seed for the assembly of a nucleocapsid from both directions, facilitating the growth of double-headed filaments with two separate RNA strings inside. Disruption of this structure by mutations in its loop interface yielded a single-headed unfunctional filament.

PurposeThis prospective phase II, open label, study was designed to assess the efficacy and safety of D-CAG induction treatment for elderly patients with newly diagnosed AML.Experimental DesignAll patients in this study were treated with decitabine of 15 mg/m2 for 5 days and G-CSF for priming, in combination with cytarabine of 10-mg/m2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days (D-CAG).ResultsAmong 85 evaluable patients, overall response rate (ORR) and complete remission (CR) were 82.4% and 64.7%, respectively, after 1 cycle of therapy. The ORR in patients aged <70 years was 83.0% and 81.6% in patients aged ≥70 years. There was a significantly longer median overall survival (OS) in patients with response (16 months) than in those without response (7 months, p< 0.0001). The OS for patients aged ≥70 years and 60-69 years was 10 months and 12 months, respectively (p=0.4994). The two-year OS probability was 19.2% and the twenty-month survival rate was 33.8%. Induction mortality of D-CAG treated elderly patients with AML is 4.4%.ConclusionD-CAG regimen was well tolerated and showed a promising clinic efficacy in elderly patients with AML (≥70 years).

Human telomerase is highly active in more than 85% of primary cancers, regardless of their tissue origins, but not in most differentiated somatic tissues. Because of this, telomerase recently has become a popular target of anticancer therapy and has been used as a marker of cancer. Similarly, telomerase promoters, especially telomerase reverse transcriptase (TERT) promoter, have been zealously tested for targeted cancer gene therapy. In vitro and in vivo studies have demonstrated that the human TERT (hTERT) promoter is highly active in human and murine cancer cells but not in normal differentiated human cells, normal human CD34 + progenitor cells, normal mouse fibroblasts, or normal mouse livers. Moreover, transcription factors can dramatically augment transgene expression from the hTERT promoter without the promoter losing its specificity. Thus far, telomerase promoters have been tested for targeted cancer gene therapy with proapoptotic, cytotoxic, and prodrug-activating genes and with replication-competent viral vectors. Here, we review recent achievements in telomerase promoter-based targeted cancer gene therapy.

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Purpose: Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome–positive chronic myeloid leukemia (CML-CP). Patients and Methods: In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n = 196) or imatinib 400 mg once daily (n = 198) groups. Results: The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; P = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; P = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; P &lt; 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P = 0.0358; 16.8% vs. 5.1%, P = 0.0002; and 23.0% vs. 11.7%, P = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm. Conclusions: Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644. See related commentary by Müller, p. 3