On March 8, 2019, the FDA granted accelerated approval to atezolizumab in combination with paclitaxel protein-bound for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 [PD-L1 stained tumor-infiltrating immune cells (IC) of any intensity covering ≥1% of the tumor area], as determined by an FDA-approved test. Approval was based on data from IMpassion130, which randomized patients to receive atezolizumab...
Fri May 15, 2020 10:05
Purpose:Although stereotactic body radiotherapy (SBRT) is effective in early-stage non–small cell lung cancer (NSCLC), approximately 10%–15% of patients will fail regionally and 20%–25% distantly. We evaluate a novel circulating tumor cell (CTC) assay as a prognostic marker for increased risk of recurrence following SBRT. Experimental Design:Ninety-two subjects (median age, 71 years) with T1a (64%), T1b (23%), or T2a (13%) stage I NSCLC treated with SBRT were prospectively enrolled. CTCs were enumerated...
Fri May 15, 2020 10:05
Purpose:Immune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART). Patients and Methods:We performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort...
Fri May 15, 2020 10:05
Purpose:Pancreatic cancer remains a disease of high mortality despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic cancers. MUC1 and MUC4 expression are related to the aggressive behavior of human neoplasms and a poor patient outcome. In contrast, MUC2 is a tumor suppressor, and we have previously reported that MUC2 is a favorable prognostic factor in pancreatic neoplasia. This study investigates whether the methylation status...
Fri May 15, 2020 10:05
Purpose:Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL). Improving outcomes by targeting mechanisms of drug resistance is a potential solution. Patients and Methods:We report results investigating the epigenetic modulators decitabine and vorinostat with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase for pediatric patients with relapsed or refractory B-cell ALL (B-ALL). Twenty-three patients, median age 12 years (range,...
Fri May 15, 2020 10:05
Fri May 15, 2020 10:05
Purpose:ABBV-838 is an antibody–drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-838 in patients with relapsed and refractory multiple myeloma (RRMM). Patients and Methods:Eligible patients (≥18 years) received ABBV-838 (3+3 design) intravenously starting from...
Fri May 15, 2020 10:05
Purpose:We aimed to analyze and compare leukocyte telomere length (LTL) and age-dependent LTL attrition between childhood cancer survivors and noncancer controls, and to evaluate the associations of LTL with treatment exposures, chronic health conditions (CHC), and health behaviors among survivors. Experimental Design:We included 2,427 survivors and 293 noncancer controls of European ancestry, drawn from the participants in St. Jude Lifetime Cohort Study (SJLIFE), a retrospective hospital-based...
Fri May 15, 2020 10:05
Purpose:The effectiveness of immune checkpoint inhibitors (ICI) is limited in pancreatic ductal adenocarcinoma (PDAC). We conducted a phase I study to evaluate the safety of ICI with stereotactic body radiation therapy (SBRT) in patients with metastatic PDAC. Patients and Methods:Patients enrolled must have received at least one line of prior systemic chemotherapy for metastatic disease. Cohorts A1 and A2 received durvalumab every 2 weeks plus either 8 Gy in one fraction of SBRT on day 1 or 25 Gy...
Fri May 15, 2020 10:05
Purpose:To examine the effect of oncolytic herpes simplex virus (oHSV) on NOTCH signaling in central nervous system tumors. Experimental Design:Bioluminescence imaging, reverse phase protein array proteomics, fluorescence microscopy, reporter assays, and molecular biology approaches were used to evaluate NOTCH signaling. Orthotopic glioma-mouse models were utilized to evaluate effects in vivo. Results:We have identified that herpes simplex virus-1 (HSV-1; oncolytic and wild-type)-infected glioma...
Fri May 15, 2020 10:05
Purpose:Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods:Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone....
Fri May 15, 2020 10:05
Purpose:Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant–comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with acute myeloid leukemia and myelodysplastic syndrome. Here we aimed to validate and prove the generalizability...
Fri May 15, 2020 10:05
Purpose:Patients with recurrent or metastatic neuroendocrine neoplasms (NEN) had a poor prognosis and few treatment options. Toripalimab, a humanized IgG4 antibody specific for human PD-1 receptor, was first approved to treat second-line metastatic melanoma in China in 2018. Patients and Methods:The multiple-center phase Ib trial enrolled patients with NENs (Ki-67 ≥ 10%) after failure of first-line therapy received 3 mg/kg toripalimab once every two weeks. The primary objective was objective response...
Fri May 15, 2020 10:05
Purpose:Copy-number changes and translocations have been studied extensively in many datasets with long-term follow-up. The impact of mutations remains debated given the short time to follow-up of most datasets. Experimental Design:We performed targeted panel sequencing covering 125 myeloma-specific genes and the loci involved in translocations in 223 newly diagnosed myeloma samples recruited into one of the total therapy trials. Results:As expected, the most commonly mutated genes were NRAS, KRAS,...
Fri May 15, 2020 10:05
Purpose:Ruxolitinib with lenalidomide and dexamethasone shows antimyeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. Therefore, a phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory multiple myeloma (RRMM) who had been treated with lenalidomide/steroids...
Fri May 15, 2020 10:05
Purpose:The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non–small cell lung cancer (mNSCLC) has not been explored. Experimental Design:A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.gov identifier: NCT03047616)....
Fri May 15, 2020 10:05
Fri May 15, 2020 10:05
Overexpression of survivin plays a crucial role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, survivin has been proposed as an attractive target for new anti-tumor interventi...
Thu May 14, 2020 03:00
Abstract Objectives Since the third century CE, a series of nomadic tribes have been active on the eastern part of the Mongolian Plateau. Characterizing the genetic compositions of past nomadic people is significant for research on the nomadic cultures of the Eurasian Steppe region. Ancient DNA analysis facilitates a deeper understanding of the relationship between historical and modern nomadic populations. Materials and methods Whole‐genome shotgun sequencing and capture sequencing of...
Thu May 14, 2020 17:45
Aim/Objectives/Background: To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation. Methods: The ACR–ASTRO Practice...
Tue May 12, 2020 03:00
The Journal of Antibiotics, Published online: 15 May 2020; doi:10.1038/s41429-020-0313-6N-Terminal guanidine derivatives of teicoplanin antibiotics strongly active against glycopeptide resistant Enterococcus faecium
Fri May 15, 2020 03:00
Abstract Polyhydroxyalkanoates (PHA), polyesters accumulated by numerous prokaryotes in the form of intracellular granules, have been for decades considered being predominantly storage molecules. However, numerous recent discoveries revealed and emphasized their complex biological role for microbial cells. Most of all, it was repeatedly reported and confirmed that the presence of PHA granules in prokaryotic cells enhances stress resistance and robustness...
Fri May 15, 2020 08:48
This corrects the article "Emerging technologies for the pretreatment of lignocellulosic materials for bio-based products” in volume 104, with page no 455–473, (https://doi.org/10.1007/s00253-019-10158-w).
Fri May 15, 2020 08:48
Abstract Serine protease inhibitors (serpins) are involved in inflammation, coagulation, fibrinolysis, tumor suppression, molecular chaperone, chromatin densification, and hormone transport. However, their anti-intoxication activity has not been determined. Here, we heterologously expressed the serpin gene from Lentinula edodes in Escherichia coli and purified the recombinant serpin protein from L. edodes (rLeSPI). Then, we administered alcohol and active protein or Haiwangjinzun...
Fri May 15, 2020 08:48
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