tbuckley/cabot-search huggingface dataset:
CBIO-23. A NOVEL ANTI-APOPTOTIC ROLE OF PON2 IN GLIOMA
Authors: Edlira Hoxha
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) represents the most common primary malignant brain tumor with dismal prognosis. Apoptosis evasion is one of the major contributors to treatment failure in GBM. PON2 (Paraoxonase-2), a member of paraoxonase family, is an anti-oxidant enzyme that is implicated in atherosclerosis, diabetes, and neurodegenerative diseases. Recent evidence showed that PON2 promotes apoptosis resistance in the selected tumor cells. However, expression or function of PON2 in brain tumor is unknown. Mining through multiple independent glioma datasets, we showed that PON2 is upregulated in gliomas compared to non-tumor brains. In addition, PON2 protein level was high in human gliomas and patient-derived glioma sphere cultures (GSC). Using transcriptome- and genome-wide analysis, we showed that PON2 expression is positively regulated by NFIA (Nuclear Factor I-A), a glioma-promoting transcription factor, and that PON2 and NFIA expression is highly correlated in GBM. Moreover, functional studies showed that PON2 prevents GSC from etoposide-induced cell death, which is reversed by genetic knockdown of NFIA. NFIA positively regulated PON2 transcription through direct binding to the PON2 promoter. Together, these data suggest that the anti-apoptotic effect of PON2 is at least partly mediated by NFIA in GBM, advancing our understanding of the emerging role of PON2 in glioma, which may open new insights into therapy by targeting relevant pathways.
Whole Genome Sequencing Identifies Four Novel Variants in the Epidermal Differentiation Complex That Increase Risk and Severity for Atopic Dermatitis
Authors: Rasika A. Mathias, Sameer Chavan, Meher Boorgula, William O.C. Cookson, Saffron Willis-Owen, Nicholas M. Rafaels, Jon M. Hanifin, Amy Paller, Lynda C. Schneider, Richard Gallo, Emma Guttman-Yassky, Peck Y. Ong, Ingo Ruczinski, Terri Beaty, Li Gao, Lisa A. Beck, Miriam Moffat, Donald Y.M. Leung, Kathleen C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2017)
Chromosome 14 Copy Number-Dependent IGH Gene Rearrangement Patterns in High Hyperdiploid Childhood B Cell Precursor ALL: Implications for Leukemia Biology and Minimal Residual Disease Analysis.
Authors: Eva Csinady, Vincent van der Velden, Ulrike Kaindl, Ruth Joas, Jelteje de Vries, Berna Beverloo, Jacques van Dongen, Georg Mann, Oskar A. Haas, Renate Panzer-Grümayer
Journal: Blood (2008)
Nonconvulsive status epilepticus in cancer patients with altered mental status.
Authors: Barbara Jane O'Brien, Jacob Joseph Mandel, Tummala Sudhakar, John Frederick De Groot
Journal: Journal of Clinical Oncology (2014)

e13028 Background: Non-convulsive status epilepticus (NCSE) is a potentially treatable etiology of unexplained altered mental status (AMS) in cancer patients. NCSE may be under-recognized clinically making electroencephalogram (EEG) essential for diagnosis. The purpose of this study was to determine the incidence of NCSE among patients with cancer undergoing inpatient neurology consultation for AMS, and to characterize their clinical features. Methods: We retrospectively reviewed the clinical records of 512 patients undergoing neurology consult for AMS between 1/1/2010-12/30/2011, and identified those with a diagnosis of NCSE. Basic demographics, primary cancer, clinical presentation, clinical course, and outcomes data were collected. Results: 21 patients were diagnosed with NCSE by EEG, an incidence of 4%. Of the 21, 3 had prior history of seizures and were maintained on antiepileptic drugs (AEDs). Ten had a solid primary cancer, 11 had a hematologic primary cancer, of which 6 were post-transplant. Eleven were on active cancer treatment, and 5 were in remission. Eight (38%) had new or progressing CNS disease identified on neuroimaging. Toxic-metabolic, infectious, and CNS disease etiologies were the most commonly proposed inciting factors. Six (29%) were admitted with AMS, while 15 (71%) developed AMS during their hospitalization. Two experienced convulsive seizures during the hospitalization, prior to developing NCSE. Five were awake at time of consult, 7 were lethargic, and 9 were in a coma. Eight required intubation and/or EEG burst suppression (anesthetic suppression of epileptic activity) for control; 3 were refractory to AEDs. Eleven (52%) died or were placed in hospice during hospitalization, and died a median of 20 days following NCSE; 5 had new or progressive CNS disease. Nine of the 10 not placed in hospice died, at a median of 232 days. Of all patients, 30-day mortality was 29% (6/21) following NCSE, and 90-day mortality was 57% (12/21). Conclusions: Our findings suggest that NCSE is an important consideration for any patient with cancer and AMS. While treatment with AEDs may control NCSE, the diagnosis may suggest a poor prognosis. Further study identifying the benefit of early EEG and AEDs is warranted.
Primary analysis of a randomized phase II, multicenter trial: Neoadjuvant weekly nab-paclitaxel 100mg/m<sup>2</sup> followed by FE<sub>100</sub>C compared with docetaxel 75mg/m<sup>2</sup> followed by FE<sub>100</sub>C for early breast cancer in Japan.
Authors: Takashi Kuwayama, Hideko Yamauchi, Toshimi Takano, Koichiro Tsugawa, Takanobu Sato, Akira Kitani, Naoki Hayashi, Hiromi Okuyama, Seigo Nakamura
Journal: Journal of Clinical Oncology (2015)

136 Background: Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) is a new solvent free taxane-based anticancer drug. According to CA024 trial, nab-PTX 100mg/m 2 demonstrated superior response to docetaxel (DTX) in patients with metastatic breast cancer. Besides, nab-PTX 100mg/m 2 was less toxicity. In operable breast cancer, GeparSepto study was reported that the pCR rate were significantly higher with nab-PTX 125/150 mg/m 2 compared to paclitaxel. We planned the randomized parallel design phase II trial to evaluate nab-PTX 100mg/m 2 in early breast cancer. Methods: Stage II-III HER2-negative breast cancer patients were included in this trial and received either 4 cycles of DTX (75 mg/m 2 day1) q 3 w or 4 cycles of nab-PTX (100 mg/m 2 day1/8/15) q4w followed by 4 cycles of FE 100 C. The primary end point is pCR (ypT0/is ypN0) rate, and the secondary end points are response rate, histological effect of treatment, breast conservation rate, and toxicity. Results: Between March 2011 to March 2014, 152 eligible patients were enrolled at 6 centers (75 pts were allocated for nab-PTX). Baseline characteristics were well balanced; median age was 51/49 years (DTX/nab-PTX), 61/61% of the patients with ER positive, 38/36% triple negative breast cancer, 57/65% Ki67 &gt; 20%. Clinically response rate was similar to each drug. (53/57%) The pCR rate was 12/17% (p = 0.323). In TNBC group, the pCR rate was 28/30% (p = 0.866). In Ki67 &gt; 20% group, the pCR rate was significantly higher, 16/48% (p = 0.021) with nab-PTX arm. The most common grade3-4 adverse event was neutropenia, which was observed in 40/36% of cases. Non-hematological adverse events of any grade were; 34/32% myalgia (DTX/nab-PTX), 42/35% arthralgia, 55/65% peripheral sensory neuropathy. No Grade3-4 peripheral sensory neuropathy was observed in nab-PTX arm. Infusion reaction of DTX occurred in 1 patient. Conclusions: In this initial effectively analysis, neoadjuvant weekly nab-paclitaxel 100mg/m 2 were promising drug in HER2-negative operable breast cancer patients. Larger studies will be needed to evaluate neoadjuvant weekly nab-paclitaxel compared with DTX. Clinical trial information: 000005388.
Influence of HLA-C Matching on aGvHD of Unrelated and Family Donor Hematopoietic Stem Cell Transplantation in Pediatric Patients with Hematologic Malignancies.
Authors: Juergen Enczmann, Roland Meisel, Karsten Ogrzewalla, Gesine Kögler, Hans-Jürgen Laws, Christof Kramm, Benedikt Bernbeck, Anja Tröger, Peter Wernet, Ulrich Göbel, Dagmar Dilloo
Journal: Blood (2005)
Evaluation of the radiosensitizing potential of clofarabine in six xenograft models.
Authors: Murray Stackhouse, Karen Gilbert, Jeffrey Scoggins, William Waud
Journal: Cancer Research (2008)

421  We have previously shown that clofarabine radiosensitizes DLD-1 colon tumor xenografts (Proc. Amer. Assoc. Cancer Res. 48: 1196). The purpose of the current study was to determine whether other tumor xenograft histiotypes can be radiosensitized by clofarabine. Gemcitabine was used as a comparison for radiosensitization in all studies. We investigated six other xenograft models: NCI-H460 lung, SR475HN head and neck, SF-295 glioblastoma, DU-145 prostate, PANC-1 pancreatic, and HCT-116 colon. Mice were implanted with tumor fragments subcutaneously from an in vivo passage and the tumors were allowed to grow. Mice with tumors in the designated size range were selected for the studies. The NCI-H460 and SF-295 studies used 12 Gy total radiation delivered in four, 3 Gy fractions every three days combined with clofarabine injected by intraperitoneal (ip) injection daily for 10 days at a dosage of 30 mg/kg/injection. The remaining tumor models were given 20 Gy, in 2 Gy fractions daily for five days for two weeks combined with clofarabine injected ip daily for 12 days at a dosage of 30 mg/kg/injection. Clofarabine had no effect on the growth of SF-295 glioblastoma which was not enhanced by radiation. There was no difference between radiation alone and radiation combined with clofarabine in DU-145 prostate xenografts. The combined effect on NCI-H460 lung tumors appeared to be additive with T-C values (based on time to 3 tumor doublings) of 4.6, 9.4, and 16.9 days for clofarabine, radiation, and the combination, respectively. SR475HN head and neck tumors were radiosensitized by clofarabine with T-C values (based on 2 tumor doublings) of 16.7, 73.2, and >162 days for clofarabine, radiation, and the combination, respectively. PANC-1 pancreatic tumors were radiosensitized by clofarabine with T-C values (based on 2 tumor doublings) of 17.2, 1.7, and 62.9 days for clofarabine, radiation, and the combination, respectively. HCT-116 colon tumors were radiosensitized by clofarabine with T-C values (based on 3 tumor doublings) of 24.2, 29.3, and >78.9 days for clofarabine, radiation, and the combination, respectively. The radiosensitizing capacity of gemcitabine tracked with the clofarabine results. Three out of the six tumor models tested showed marked radiosensitization with clofarabine while another tumor model showed an additive effect. Two out of the six models tested showed no evidence of an interaction between clofarabine and radiation. Clofarabine has potential as a radiosensitizing cancer treatment.
Challenges in the implementation of survivorship care plans in an NCI-designated cancer center.
Authors: Mary Mendelsohn, Joanne E. Mortimer, Leslie Popplewell, Lily L. Lai, Ellie Maghami, Denice Economou
Journal: Journal of Clinical Oncology (2016)

68 Background: The development and initiation of Survivorship Care Plans (SCPs) across all disease sites was identified as a Strategic Initiative Goals for 2015 by the Clinical Cancer Committee. The 2012 Commission on Cancer requirements for certification provided an additional incentive to meet this goal. Establishing a process that includes the development and distribution of a SCP’s within the electronic medical record (EMR) is necessary to improve on the completion of SCP’s and to improve the utilization of surveillance tests in cancer survivors. We describe the process developed at a free-standing NCI cancer center to meet the standard of SCP provision to all cancer patients. Methods: A multi-disciplinary subcommittee of the Cancer Committee was designated to develop the overall strategic plan for the implementation of this standard. It met with disease teams to facilitate a treatment summary from Cancer Registry data, identify patient reported symptoms using a self report tablet (SupportScreen). Electronic care plans were created using survivorship research program templates and ASCO framework for each disease site team. The disease team Nurse Care Coordinator inputs information into the eSCP. Results: Templates have been established within the EMR in the documents section under survivorship care plan title. These can be initiated and modified when the Nurse Care Coordinator chooses to start them. The disease teams have established their time points for SCP presentation to their patients. Using the cancer registry to provide data related to staging, treatments and genetic testing has helped minimize development time. Individual survivor’s concerns will be reflected in patient reports and physician symptom documentation. This eSCP completion process is a pilot program within the breast cancer disease team and will be expanded to include patients with head &amp; neck and hematologic malignancies with a goal of including all patients by mid 2016. Conclusions: The goal of improving survivorship care coordination and compliance with surveillance guidelines is challenging. Maximizing available interdisciplinary resources has helped to create a viable Survivorship Care plan at our institution.
Evidence of reactivation of hepatitis B virus in patients receiving chemotherapy for malignancies
Authors: Masafumi Ikeda, Hideaki Takahashi, Yusuke Hashimoto, Izumi Ohno, Shuichi Mitsunaga, Kumiko Umemoto, Kazuo Watanabe, Takuji Okusaka
Journal: Annals of Oncology (2016)
A Novel Functional Role for Soluble CD27 in the Pathogenesis of Waldenstrom’s Macroglobulinemia.
Authors: Allen W. Ho, Xavier Leleu, Evdoxia Hatjiharissi, Olivier Tournilhac, Lian Xu, Kelly O’Connor, Robert Manning, Daniel Santos, Mariana Chemaly, Andrew Branagan, Zachary Hunter, Christopher Patterson, Kenneth C. Anderson, Steven P. Treon
Journal: Blood (2005)
STMC-06. QKI DELETION ENHANCES SELF-RENEWAL OF GLIOMA STEM CELLS AND PROMOTES GLIOMAGENESIS
Authors: Jian Hu, Takashi Shingu
Journal: Neuro-Oncology (2016)

Glioma stem cells (GSCs) have higher self-renewal capacity than neural stem cells (NSCs). However it is still not clear how GSCs enhance their self-renewal and whether or not enhanced self-renewal alone without affecting cell proliferation can promote gliomagenesis. Here we report the generation of a novel conditional KO allele of QKI, a tumor suppressor in GBM with RNA binding motif. When QKI was deleted in NSCs isolated from subventricular zone of Nestin-CreERT2 QKIL/L mice, multiple NSC markers were dramatically increased. When QKI was deleted in adult Nestin-CreERT2 QKIL/L mice, the NSC population, which is characterized by long-term BrdU retention and GFAP+/Nestin+ double positive staining, was greatly increased, indicating that deletion of QKI enhances NSC self-renewal. To determine whether QKI deletion promotes gliomagenesis, we generated a Nestin-CreERT2 QKIL/LPtenL/LP53L/L cohort, in which 92% of the mice developed glioblastoma starting at 2 months. However, the Nestin-CreERT2 PtenL/LP53L/L cohort did not develop any glioma up to a year; therefore QKI deletion greatly promotes gliomagenesis. Transcriptomic and proteomic profiling coupled with PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) analyses revealed that genes involved in receptor trafficking were greatly enriched by QKI deletion. Specifically, 34% of the genes up-regulated by QKI deletion are involved in receptor delivery, and 39% of the genes down-regulated by QKI deletion are subunits of receptor degradation machineries such as endosomes and lysosomes. High level of receptor delivery and low level of receptor degradation concomitantly enrich receptors on the membrane and enhance the activity of the receptors that are involved in maintaining stemness, including RTK, Notch1 and Frizzled. Inhibition of the activity of receptors can diminish the enhanced self-renewal and decreased differentiation caused by QKI deletion. Taken together, our data suggest that QKI deletion increases receptor delivery and decreases endocytosis-mediated degradation, consequently enhancing the receptor activity and self-renewal capacity.
Impact of FLT3-ITD Mutational Burden in 469 Acute Myeloid Leukemia (AML) Patients
Authors: Pierre Hirsch, Myriam Labopin, Christophe Marzac, Anne-Claire Mamez, Ruoping Tang, Françoise Isnard, Simona Lapusan, Anne Vekhoff, Norbert C Gorin, Jean-Pierre Marie, Mohamad Mohty, Ollivier Legrand
Journal: Blood (2014)
Potential Impact of Pathologic Review on Therapy in Non-Hodgkin’s Lymphoma (NHL): Analysis from the National Comprehensive Cancer Network (NCCN) NHL Outcomes Project.
Authors: Ann LaCasce, Joyce Niland, Michelle E. Kho, Anna terVeer, Jonathan W. Friedberg, Maria A. Rodriguez, Myron S. Czuczman, Michael Millenson, Andrew D. Zelenetz, Auayporn P. Nademanee, Jane C. Weeks
Journal: Blood (2005)
149O The National University Cancer Institute, Singapore (NCIS) Integrated Molecular Analysis of Cancer (IMAC) precision oncology programme: Frequency of actionable mutations and outcomes following matched therapy in an Asian Cancer Centre
Authors: N. Syn, V. Heong, X.W. Lee, N.S. Sapari, X.Q. Koh, Z. Fazreen, J.S.Y. Lim, B. Pang, D. Lim, A.L-A. Wong, R.A. Soo, W-P. Yong, C-E. Chee, S-C. Lee, B-C. Goh, R. Soong, D.S. Tan
Journal: Annals of Oncology (2016)
Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas
Authors: Hannah Wang, Pauline Funchain, Gurkan Bebek, Jessica Altemus, Huan Zhang, Farshad Niazi, Charissa Peterson, Walter T. Lee, Brian B. Burkey, Charis Eng
Journal: Genome Medicine (2017)

While the role of the gut microbiome in inflammation and colorectal cancers has received much recent attention, there are few data to support an association between the oral microbiome and head and neck squamous cell carcinomas. Prior investigations have been limited to comparisons of microbiota obtained from surface swabs of the oral cavity. This study aims to identify microbiomic differences in paired tumor and non-tumor tissue samples in a large group of 121 patients with head and neck squamous cell carcinomas and correlate these differences with clinical-pathologic features. Total DNA was extracted from paired normal and tumor resection specimens from 169 patients; 242 samples from 121 patients were included in the final analysis. Microbiomic content of each sample was determined using 16S rDNA amplicon sequencing. Bioinformatic analysis was performed using QIIME algorithms. F-testing on cluster strength, Wilcoxon signed-rank testing on differential relative abundances of paired tumor-normal samples, and Wilcoxon rank-sum testing on the association of T-stage with relative abundances were conducted in R. We observed no significant difference in measures of alpha diversity between tumor and normal tissue (Shannon index: p = 0.13, phylogenetic diversity: p = 0.42). Similarly, although we observed statistically significantly differences in both weighted (p = 0.01) and unweighted (p = 0.04) Unifrac distances between tissue types, the tumor/normal grouping explained only a small proportion of the overall variation in the samples (weighted R2 = 0.01, unweighted R2 < 0.01). Notably, however, when comparing the relative abundances of individual taxa between matched pairs of tumor and normal tissue, we observed that Actinomyces and its parent taxa up to the phylum level were significantly depleted in tumor relative to normal tissue (q < 0.01), while Parvimonas was increased in tumor relative to normal tissue (q = 0.01). These differences were more pronounced among patients with more extensive disease as measured by higher T-stage. Matched pairs analysis of individual tumor-normal pairs revealed significant differences in relative abundance of specific taxa, namely in the genus Actinomyces. These differences were more pronounced among patients with higher T-stage. Our observations suggest further experiments to interrogate potential novel mechanisms relevant to carcinogenesis associated with alterations of the oral microbiome that may have consequences for the human host.
321P Clinical course comparison between patients with type 1 and type 2 uterine endometrial cancers
Authors: Y. Takehara, M. Yunokawa, S. Sasada, E. Noguchi, A. Shimomura, T. Shimoi, K. Yonemori, C. Shimizu, T. Kato, K. Tamura
Journal: Annals of Oncology (2016)
Activity of single-agent bevacizumab (B) in patients with metastatic renal cell carcinoma (RCC) previously treated with VEGF- and mTOR-based therapies.
Authors: Andrew J. Armstrong, James D. Turnbull, Julien Cobert, Tracy Jaffe, Michael Roger Harrison, Daniel J. George
Journal: Journal of Clinical Oncology (2012)

435 Background: Given a lack of clinical information on therapeutic efficacy of agents following progression after vascular endothelial growth factor (VEGF) tyrosine kinase inhibition (TKI) and mammalian target of rapamycin (mTOR) inhibition in metastatic renal cell carcinoma (mRCC), we investigated the activity of single agent bevacizumab (B) in this setting. Methods: We conducted a retrospective analysis of single agent B-treated patients with mRCC in the second/third line setting, and identified 21 subjects who met inclusion criteria. The primary endpoint was progression-free survival (PFS). Baseline characteristics, survival, response efficacy outcomes, and toxicities were assessed and summarized. Results: 21 patients (15 women/6 men) were treated with B at a dose of 5 mg/kg/week, dosed q2-3 weeks. Median age was 63, 80% were white, 14% black; 80% had clear cell histology. Median time from diagnosis to B therapy was 3 years (range 1-18); 100% had prior VEGF TKI therapy; 43% had prior mTOR inhibitor; 43% had prior IFN and 19% prior IL-2; median number of prior therapies was 3 (range 1-7); 100% were considered Motzer intermediate risk. Median PFS on B for all subjects was 4.4 mo (95% CI 2.8-9.6) and median OS was 19.4 mo (95% CI 9.9-NR) from start of B therapy. ORR was 2 CR/PR (9.5%), 11 SD (52%), 5 PD, 3 NE. For subjects treated with prior VEGF and mTOR inhibitors, median PFS and OS were 4.4/13.2 mo. Toxicities were as expected and severe adverse events included grade 3-4 fatigue (6), grade 3-4 dehydration (5), and grade 4 failure to thrive (2), grade 4 constipation (2), and grade 3 muscle weakness (2). Conclusions: Single agent B therapy has acceptable toxicity and moderate disease stabilizing activity in selected patients with mRCC who have failed prior VEGF TKI and mTOR inhibitor therapy, and suggests a benefit to continued ongoing VEGF inhibition. Further prospective study of B alone, in combination with mTOR inhibition, or with alternative targeted agents is warranted.
448PD Association between EGFR T790M status and progression patterns during initial EGFR-TKIs treatment in patients harboring EGFR mutation
Authors: Y. Oya, T. Yoshida, K. Tanaka, H. Kuroda, J. Shimizu, Y. Horio, Y. Sakao, Y. Inaba, T. Hida, Y. Yatabe
Journal: Annals of Oncology (2016)