tbuckley/cabot-search huggingface dataset:
Efficacy and safety of rhLTα-Da with cisplatin and fluorouracil in patients with metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open-labelled, controlled, phase IIb trial.
Authors: Yu-hong Li, Wenqi Jiang, Fenghua Wang, Guo-ping Sun, Jianhua Chen, Lin Ying Cheng, Wei Liu, Rong-sheng Zheng, Jia Chen, Helong Zhang, Hai-tao Lan, Jun Qi, Yang-qing Liu, Yan-ming Deng, Heng Zhao, Jian ping Xiong, Qing Xu
Journal: Journal of Clinical Oncology (2016)

4036 Background: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is the LTα derivative without N-terminal 27 amino acid residues. Our prior studies showed that the addition of rhLTα-Da to cisplatin-based treatment was tolerable and had an encouraging response rate in metastatic esophageal squamous cell carcinoma (mESCC). This randomized, multicenter, controlled, phase II b trial was conducted to evaluate the efficacy and safety of rhLTα-Da with cisplatin and fluorouracil (PF) as the first-line therapy for mESCC (ChiCTR-TRC-11001197). Methods: Patients from 15 centers in China were randomly assigned (1:1:1) into three arms (arm A, PF + 10 μg/m2/d rhLTα-Da; arm B, PF + 20 μg/m2/d rhLTα-Da, arm C, PF alone). The primary endpoints included progression-free survival (PFS) and confirmed overall response rate (ORR). An explanatory analysis was performed to evaluate the role of serum tumor necrosis factor receptor-II (TNFR-II) in predicting the efficacy of rhLTα-Da. Results: Between September 2010 and May 2013, 150 patients were enrolled. Baseline patients characteristics were similar between arms. No significant difference in either PFS or ORR was observed between these arms. The median PFS was 3.9 months (95% confidence interval [CI]: 2.9-5.3 months) in arm A, 5.7 months (95% CI: 3.2-6.8 months) in arm B, and 4.9 months (95% CI: 3.1-6.1 months) in arm C (P = 0.248); the ORR was 27.1% in arm A, 46.8% in arm B, and 41.7% in arm C (P = 0.073). However, among patients with low levels of serum TNFR-II, the median PFS was significantly longer in arm B than in other two arms (7.2 months [95% CI: 5.1-8.6 months] in arm B vs. 3.5 months [95% CI: 1.7-5.5 months] in arm A [P= 0.022] and 4.0 months [95% CI: 3.2-6.3 months] in arm C [P = 0.027]). The addition of rhLTα-Da to PFdidn't add AEs statistically. Conclusions: Although the primary endpoint was not met, the addition of high-dose rhLTα-Da to PF regimen may prolong PFS in mESCC patients with low levels of serum TNFR-II. Further prospective study in selected patients is warranted. Clinical trial information: ChiCTR-TRC-11001197.
Quantification of intratumoral heterogeneity of HER2 status in breast cancer.
Authors: Rie Horii, Masaaki Matsuura, Hiro Nitta, Yoshinori Ito, Shinji Ohno, Takuji Iwase, Futoshi Akiyama
Journal: Journal of Clinical Oncology (2017)

1036 Background: Intratumoral heterogeneity (ITH) occurs as a consequence of epigenetic aberrations in tumor cells with genetic diversity. HER2 ITH can be classified into genetic (a mixture of tumor cells with and without HER2 gene amplification) and epigenetic ITH (a mixture of HER2 gene-amplified tumor cells with and without HER2 protein overexpression). However, the both effects of genetic and epigenetic ITH on HER2-targeted therapy have not been clearly demonstrated. In order to implement ITH as a referenced factor for treatment selection, the ITH quantification is necessary. Gene-protein assay (GPA), in which immunohistochemistry and dual in situ hybridization are simultaneously performed on a single slide, allows bright-field analyses of both gene and protein status. We aimed to quantify HER2 ITH by the combination of gene and protein status and clarify its clinical significance. Methods: Fifty three patients with HER2-positive breast cancer, who underwent neoadjuvant trastuzumab with chemotherapy, were examined. Five representative microscopic images were captured from a GPA slide of a pre-therapeutic biopsy material. All evaluable tumor cells in the images were scored according to the HER2 status determined by the combination of gene copy number and protein expression (Table). We investigated the relationship between the HER2 scores and pathological complete response (pCR) to the neoadjuvant treatment by the logistic analysis. Results: The average of HER2 scores, indicating the degree of the HER2 status, varied from 2.21 to 5.98. It was significantly related to pCR (Estimate: 1.21, Std. error: 0.46, RR: 3.34, P=0.009, 95%CI: 1.35-8.25). The standard deviation of HER2 scores, indicating the degree of the HER2 ITH, varied from 0.13 to 1.37. It was significantly related to pCR (Estimate: -2.09, Std. error: 0.83, RR: 0.12, P=0.012, 95%CI: 0.02-0.63). Conclusions: HER2 ITH, quantified by GPA, is a predictive factor for the therapeutic effect to trastuzumab-based treatment in HER2-positive breast cancer. [Table: see text]
Endothelin-1 promotes vascular smooth muscle cell migration across the artery wall: a mechanism contributing to vascular remodelling and intimal hyperplasia in giant-cell arteritis
Authors: Ester Planas-Rigol, Nekane Terrades-Garcia, Marc Corbera-Bellalta, Ester Lozano, Marco A Alba, Marta Segarra, Georgina Espígol-Frigolé, Sergio Prieto-González, José Hernández-Rodríguez, Sara Preciado, Rodolfo Lavilla, Maria C Cid
Journal: Annals of the Rheumatic Diseases (2017)

Background Giant-cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries, frequently involving the temporal arteries (TA). Inflammation-induced vascular remodelling leads to vaso-occlusive events. Circulating endothelin-1 (ET-1) is increased in patients with GCA with ischaemic complications suggesting a role for ET-1 in vascular occlusion beyond its vasoactive function. Objective To investigate whether ET-1 induces a migratory myofibroblastic phenotype in human TA-derived vascular smooth muscle cells (VSMC) leading to intimal hyperplasia and vascular occlusion in GCA. Methods and results Immunofluorescence/confocal microscopy showed increased ET-1 expression in GCA lesions compared with control arteries. In inflamed arteries, ET-1 was predominantly expressed by infiltrating mononuclear cells whereas ET receptors, particularly ET-1 receptor B (ET B R), were expressed by both mononuclear cells and VSMC. ET-1 increased TA-derived VSMC migration in vitro and α-smooth muscle actin (αSMA) expression and migration from the media to the intima in cultured TA explants. ET-1 promoted VSMC motility by increasing activation of focal adhesion kinase (FAK), a crucial molecule in the turnover of focal adhesions during cell migration. FAK activation resulted in Y397 autophosphorylation creating binding sites for Src kinases and the p85 subunit of PI3kinases which, upon ET-1 exposure, colocalised with FAK at the focal adhesions of migrating VSMC. Accordingly, FAK or PI3K inhibition abrogated ET-1-induced migration in vitro. Consistently, ET-1 receptor A and ET B R antagonists reduced αSMA expression and delayed VSMC outgrowth from cultured GCA-involved artery explants. Conclusions ET-1 is upregulated in GCA lesions and, by promoting VSMC migration towards the intimal layer, may contribute to intimal hyperplasia and vascular occlusion in GCA.
Notch Signaling in Bone Marrow Nestin-Expressing Cells Controls Balance of Erythropoiesis at the Bone Marrow and Spleen
Authors: Tatsuhiro Sakamoto, Naoshi Obara, Takayasu Kato, Luan Cao Sy, Hidekazu Nishikii, Mamiko Sakata-Yanagimoto, Satoru Takahashi, Shigeru Chiba
Journal: Blood (2016)
Cooperative Epigenetic Remodeling By TET2 Loss and NRAS Mutation Drives Myeloid Transformation and MEK Inhibitor Sensitivity
Authors: Hiroyoshi Kunimoto, Cem Meydan, Abbas Nazir, Kaitlyn Shank, Rebecca Maher, Franck Rapaport, Elodie Pronier, Ari Melnick, Ross L. Levine, Alan H. Shih
Journal: Blood (2016)
A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis
Authors: Melody C. Carter, Avanti Desai, Hirsh D. Komarow, Yun Bai, Sarah T. Clayton, Alicia S. Clark, Karina N. Ruiz-Esteves, Lauren M. Long, Daly Cantave, Todd M. Wilson, Linda M. Scott, Olga Simakova, Mi-Yeon Jung, Jamie Hahn, Irina Maric, Dean D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (2017)
Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain
Authors: Udo Hoffmann, Maros Ferencik, James E. Udelson, Michael H. Picard, Quynh A. Truong, Manesh R. Patel, Megan Huang, Michael Pencina, Daniel B. Mark, John F. Heitner, Christopher B. Fordyce, Patricia A. Pellikka, Jean-Claude Tardif, Matthew Budoff, George Nahhas, Benjamin Chow, Andrzej S. Kosinski, Kerry L. Lee, Pamela S. Douglas
Journal: Circulation (2017)

Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing.
MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia
Authors: Yufei Chen, Konstantinos Anastassiadis, Andrea Kranz, A. Francis Stewart, Kathrin Arndt, Claudia Waskow, Akihiko Yokoyama, Kenneth Jones, Tobias Neff, Yoo Lee, Patricia Ernst
Journal: Cancer Cell (2017)
Authors’ response to a reply to: Re: Routine usage of sentinel node biopsy in melanoma management must cease
Authors: A. Dixon, H. Steinman, S. Anderson, A. Nirenberg, J. Dixon, M. Sladden
Journal: British Journal of Dermatology (2017)

We thank Mr. Saleh for his comments and are pleased he agrees that acceptance into melanoma therapeutic trials should not be contingent on undergoing sentinel node biopsy (SNB). We disagree with his assertion that SNB still has a viable role in melanoma management. Suppose SNB followed by completion lymphadenectomy (CL) was a drug therapy for melanoma, subjected to a ten-year randomized controlled trial involving 2000 patients where a survival benefit was not found.

This article is protected by copyright. All rights reserved.
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non–Small Cell Lung Cancer
Authors: Chana Weinstock, Sean Khozin, Daniel Suzman, Lijun Zhang, Shenghui Tang, Sakar Wahby, Kirsten B. Goldberg, Geoffrey Kim, Richard Pazdur
Journal: Clinical Cancer Research (2017)

On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR.
Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells
Authors: Guinevere Q Lee, Nina Orlova-Fink, Kevin Einkauf, Fatema Z Chowdhury, Xiaoming Sun, Sean Harrington, Hsiao-Hsuan Kuo, Stephane Hua, Hsiao-Rong Chen, Zhengyu Ouyang, Kavidha Reddy, Krista Dong, Thumbi Ndung'u, Bruce D Walker, Eric S Rosenberg, Xu G Yu, Mathias Lichterfeld
Journal: Journal of Clinical Investigation (2017)

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.
Longitudinal assessment of cancer-related cognitive impairment (CRCI) up to six-months post-chemotherapy with multiple cognitive testing methods in 943 breast cancer (BC) patients and controls.
Authors: Michelle Christine Janelsins, Charles E. Heckler, Luke Joseph Peppone, Supriya Gupta Mohile, Karen Michelle Mustian, Tim Ahles, Oxana Palesh, Ann M. O'Mara, Lori M. Minasian, AnnaLynn Williams, Allison Magnuson, Karen Schmidt, Shaker R. Dakhil, Judith O. Hopkins, Gary R. Morrow
Journal: Journal of Clinical Oncology (2017)

10014 Background: Large nationwide studies are needed to assess CRCI. Methods: NCORPs recruited BC patients and age-matched non-cancer controls. Computerized ((CANTAB Delayed Match to Sample (DMS), Rapid Visual Processing (RVP), Verbal Recognition Memory (VRM)), paper-based ((Controlled Oral Word Association (COWA), and Trail Making Test (TMT)) , and phone-based (category fluency, word recall, backward counting and digits backward) cognitive assessments of memory, attention, and executive function at pre-chemotherapy, post-chemotherapy, and 6 months follow-up (or time-equivalent for controls) were completed. Longitudinal mixed model (LMM)s included group, time, time*group, and adjusted for age, education, reading, anxiety, and depression. Results: 580 BC patients (mean age = 54) and 363 controls (mean age = 53) were assessed. In all LMMs, there was a significant group*time interaction depicting lower scores in patients compared to controls (p &lt; 0.005) except for TMT (p = 0.09). For longitudinal change on the DMS memory test (primary aim), we observed no significant difference between groups from pre- to post-chemotherapy but did observe a significant difference from pre-chemotherapy to follow-up (p = 0.017) where patients significantly declined (p = 0.005) and controls did not change. We observed similar results for RVP. For VRM, there was a significant pre- to post-chemotherapy group difference (p = 0.003). For COWA, patients significantly declined and controls significantly improved reflecting a significant between group difference (p &lt; 0.001) from pre- to post-chemotherapy. For TMT, both groups significantly improved with patients improving less than controls reflected by a significant between group difference (p = 0.04) that remained a trend at follow-up (p = 0.06). On all phone tests, there was a significant between group effect from both pre- to post-chemotherapy and at follow-up with patients doing less well than controls (all p &lt; 0.001). Conclusions: This nationwide study shows CRCI in BC patients persists in multiple cognitive domains up to 6 months post-chemotherapy compared to controls. Clinical trial information: NCT01382082.
Cardiologist convicted of presenting false prescription escapes suspension
Authors: Clare Dyer
Journal: BMJ (2017)

A consultant cardiologist who was convicted of presenting false prescriptions in colleagues’ and friends’ names to support his own addiction to painkillers has had conditions imposed on his registration for 12 months.

A medical practitioners’ tribunal in Manchester also found that Martin Royle, 45, carried out five transoesophageal echocardiograms after his employer had told him to refrain from the procedure. He was also found to have worked in private practice on six occasions when on call for the NHS.

Almost all of the hearing was conducted in private, and some of the tribunal’s written determination was redacted, as is usual when a doctor’s personal health issues are germane to …
Obesity's effect on asthma extends to diagnostic criteria
Authors: Njira Lugogo, Cynthia L. Green, Noah Agada, Siyi Zhang, Susanne Meghdadpour, Run Zhou, Siyun Yang, Kevin J. Anstrom, Elliot Israel, Richard Martin, Robert F. Lemanske, Homer Boushey, Stephen C. Lazarus, Stephen I. Wasserman, Mario Castro, William Calhoun, Stephen P. Peters, Emily DiMango, Vernon Chinchilli, Susan Kunselman, Tonya S. King, Nikolina Icitovic, Monica Kraft
Journal: Journal of Allergy and Clinical Immunology (2017)
Native T1 Mapping and Extracellular Volume Mapping for the Assessment of Diffuse Myocardial Fibrosis in Dilated Cardiomyopathy
Authors: Shiro Nakamori, Kaoru Dohi, Masaki Ishida, Yoshitaka Goto, Kyoko Imanaka-Yoshida, Taku Omori, Itaru Goto, Naoto Kumagai, Naoki Fujimoto, Yasutaka Ichikawa, Kakuya Kitagawa, Norikazu Yamada, Hajime Sakuma, Masaaki Ito
Journal: JACC. Cardiovascular imaging (2017)
A Mitochondrial Etiology of Neuropsychiatric Disorders
Authors: Douglas C. Wallace
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Metformin use and survival in diabetic patients with renal cell carcinoma (RCC).
Authors: Nilay Shah, Farhad Khimani, Brendan F. Curley, Michael David Newton, Thomas F. Hogan, Sijin Wen, Yanqing Hu, Manish Monga
Journal: Journal of Clinical Oncology (2014)

e15612 Background: Diabetes Mellitus (DM) is independently associated with decreased overall survival in patients with RCC. Metformin has shown to decrease recurrence and improve survival in diabetic patients with various cancers. At present there are many clinical trials ongoing with metformin in non-diabetic patients to prevent or treat cancer. Methods: We performed an IRB approved retrospective chart review of all patients who were diagnosed with RCC at West Virginia University from 2002-2012. 598 patients with RCC were selected and stratified into two cohorts based on the presences or absence of diabetes mellitus type II (DM). The diabetic cohort was further stratified into two cohorts based on metformin use. We compared patients by age, clear cell RCC vs other histology, pathologic stage, whether or not nephrectomy was performed, smoking & alcohol use, and body mass index (BMI). Statistical analysis was performed with S-PLUS Version 7.0. Results: Of the 598 patients identified with RCC, 148 (25%) had DM and 67 (45%) of the DM patients were receiving metformin at time of RCC diagnosis. When compared to non-DM patients with RCC, the DM-RCC patients were significantly older (≥60yrs; p <0.0001), had fewer nephrectomies (p = 0.035), had less alcohol use (p = 0.018), had higher BMI (≥30; p <0.0001), and had a median OS of only 5.6 yrs vs 8.0 yrs in non-DM patients (p = 0.053). When we compared the 67 DM-metformin patients to 81 DM-non-metformin patients, there was a significant trend favoring overall survival with metformin, where users had a median OS of 7.0 yrs versus 4.6 yrs in non-users (p = 0.58). Conclusions: Based on this single institution 10-year data set, patients with DM and RCC had a significantly worse median OS as compared to their non-diabetic counterparts. Although not reaching statistical significance, diabetic RCC patients on metformin appeared to have a longer median OS as compared to those not on metformin, with a median 7.0 yr OS, fairly similar to the 8.0 yr OS in our non-diabetic patients with RCC. We believe our sample size is too small to reach a level of statistical significance and much larger studies are needed to further explore the activity of metformin in diabetics with RCC.
A phase I study of niraparib in combination with temozolomide (TMZ) in patients with advanced cancer.
Authors: Razelle Kurzrock, Evanthia Galanis, Derek Richard Johnson, Vikram Kansra, Keith Wilcoxen, Ty Mcclure, Robert E. Martell, Shefali Agarwal
Journal: Journal of Clinical Oncology (2014)

2092 Background: Niraparib (Np) is an oral, highly potent and selective PARP1/2 inhibitor. The hypothesis for this study is 1) PARP inhibition of DNA repair damage is potentiated with TMZ. 2) PARP inhibition restores sensitivity to TMZ mismatch repair-deficient tumors. Methods: This was a multi-center (3), open-label, non-randomized two-part study in patients with advanced cancers. Patients were treated with Np (once daily continuously) + TMZ (once daily for first five days) in 28-day treatment cycles. In Part A, the objective was to determine the preliminary MTD of the two drugs in combination. Part B was to explore the efficacy and tolerability of this combination in two cohorts (recurrent GBM and melanoma). The study was closed after defining MTD in Part A. Results: There were 19 patients treated in Part A with Np at 3 dose levels 30 mg (6 subjects), 40 mg (10 subjects), and 70 mg (3 subjects) and 150 mg/m2 TMZ once daily. The MTD and RP2D was determined to be 40 mg Np and 150 mg/m2 TMZ. The DLT of Grade 4 Thrombocytopenia occurred in 2/10 patients at the 40 mg dose level for Np. The DLT of Grade 4 neutropenia occurred in 1/3 patients at the 70 mg dose level for Np. At this dose level all 3 patients enrolled experienced Grade 4 thrombocytopenia with only one patient meeting protocol-specified DLT criteria. The most frequently reported AEs were thrombocytopenia (78.9%), anemia (68.4%), and leukopenia (57.9%). The most common ≥ grade 3 AEs were thrombocytopenia (52.6%), neutropenia (31.6%), and neoplasm progression (15.8%). Based on the in vitro metabolism data, the likelihood of a drug interaction between Np and TMZ is highly unlikely. Out of 16 evaluable subjects, 1 subject reported a PR (Glioblastoma), 2 subjects experienced SD (Malignant melonama and Serous ovarian carcinoma) and 13 subjects had PD. Conclusions: Niraparib, dosed at 40 mg continuously in combination with 150mg/m2 TMZ was tolerable and demonstrated antitumor activity. 40 mg Np and150 mg/m2 TMZ was considered an MTD and RP2D. A future study will evaluate full dose, 300 mg daily Np in combination with escalating TMZ dose levels. Clinical trial information: NCT01294735.