tbuckley/cabot-search huggingface dataset:
Magnetic resonance analysis of malignant transformation in recurrent glioma
Authors: Llewellyn E. Jalbert, Evan Neill, Joanna J. Phillips, Janine M. Lupo, Marram P. Olson, Annette M. Molinaro, Mitchel S. Berger, Susan M. Chang, Sarah J. Nelson
Journal: Neuro-Oncology (2016)

Patients with low-grade glioma (LGG) have a relatively long survival, and a balance is often struck between treating the tumor and impacting quality of life. While lesions may remain stable for many years, they may also undergo malignant transformation (MT) at the time of recurrence and require more aggressive intervention. Here we report on a state-of-the-art multiparametric MRI study of patients with recurrent LGG. One hundred and eleven patients previously diagnosed with LGG were scanned at either 1.5 T or 3 T MR at the time of recurrence. Volumetric and intensity parameters were estimated from anatomic, diffusion, perfusion, and metabolic MR data. Direct comparisons of histopathological markers from image-guided tissue samples with metrics derived from the corresponding locations on the in vivo images were made. A bioinformatics approach was applied to visualize and interpret these results, which included imaging heatmaps and network analysis. Multivariate linear-regression modeling was utilized for predicting transformation. Many advanced imaging parameters were found to be significantly different for patients with tumors that had undergone MT versus those that had not. Imaging metrics calculated at the tissue sample locations highlighted the distinct biological significance of the imaging and the heterogeneity present in recurrent LGG, while multivariate modeling yielded a 76.04% accuracy in predicting MT. The acquisition and quantitative analysis of such multiparametric MR data may ultimately allow for improved clinical assessment and treatment stratification for patients with recurrent LGG.
Response to Letter Regarding Article, “Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A Decade in Review”
Authors: Kimberly G. Harmon, Irfan M. Asif, Joseph J. Maleszewski, David S. Owens, Jordan M. Prutkin, Jack C. Salerno, Monica L. Zigman, Rachel Ellenbogen, Ashwin Rao, Michael J. Ackerman, Jonathan A. Drezner
Journal: Circulation (2016)
False-Positive Elevations of Carcinoembryonic Antigen in Patients With a History of Resected Colorectal Cancer
Authors: Anya Litvak, Andrea Cercek, Neil Segal, Diane Reidy-Lagunes, Zsofia K Stadler, Rona D Yaeger, Nancy E Kemeny, Martin R Weiser, Melissa S Pessin, Leonard Saltz
Journal: Journal of the National Comprehensive Cancer Network (2014)

Routine monitoring of carcinoembryonic antigen (CEA) levels is standard in patients with resected colorectal cancer (CRC). The incidence of false-positives and the upper limits of false-positive elevations have not been previously well characterized. A search of medical records at Memorial Sloan-Kettering Cancer Center identified 728 patients who underwent an R0 resection of locoregional CRC between January 2003 and December 2012 and who had an increase in CEA level above the normal range after a normal perioperative CEA level. Of these, 358 had a false-positive elevation of CEA level, 335 had a true-positive elevation indicative of recurrent CRC, and 35 had a true-positive elevation indicative of the development of a new, non-CRC malignancy. Of those with false elevations, 111 had a single isolated CEA level elevation (median highest CEA level of 5.5 ng/mL) with no further abnormal measurements, whereas 247 had elevations on 2 or more readings, with a median highest level of 6.7 ng/mL. Of these 247 patients with confirmed false-positive CEA level elevations, only 5 (2%) had measurements greater than 15 ng/mL, and no confirmed elevation greater than 35 ng/mL was a false-positive. False-positive CEA test results in the range of 5 to 15 ng/mL are common. Confirmation of CEA elevation in this range before initiating imaging studies may be appropriate. False-positive results greater than 15 ng/mL are rare, and all confirmed CEA levels greater than 35 ng/mL were associated with cancer recurrence.
HCP-14GLIOBLASTOMA MULTIFORME AMONG ELDERLY: A SINGLE INSTITUTION EXPERIENCE
Authors: Sarah Lapointe, Marie Florescu, David Simonyan, Karine Michaud
Journal: Neuro-Oncology (2015)

BACKGROUND: Treatment of glioblastoma multiforme (GBM) among patients older than 70 with standard 60Gy radiotherapy (SRT) plus temozolomide (TMZ) is challenging in terms of tolerability. Hypofractionated RT (HRT) alone or combined with TMZ is proposed, but results of these prospective randomized trials with favourable KPS patients are pending. METHODS: We retrospectively reviewed all GBM patients aged over 55 treated in our institution from 2010 to 2014. Demographic and tumor characteristics were extracted. Log-rank test and Cox proportional hazards model were used to estimate Kaplan Meier survival and hazard ratio. We divided our cohort in 4 groups according to treatment: concomitant chemoradiotherapy (CCRT) with SRT; CCRT with HRT; HRT alone; TMZ alone. RESULTS: Among the 171 patients identified, the median overall survival (mOS) in patients <70 years was 14.4mo [95%CI(11.7-16.8)] compared with mOS of patients ≥70 years 11.1mo [95%CI(6.1-16.6)] (p = 0.312). 109 patients were treated with CCRT-SRT compared to 15 with CCRT-HRT, 17 with RT alone, and 7 with TMZ alone. There was no difference in the mOS of patients receiving CCRT-SRT [14.2mo 95%CI(12.2-16.8)] compared with CCRT-HRT [14.6mo 95%CI(4.0-17.9)]. Patients on TMZ monotherapy had a poor mOS [4.4mo 95%CI(1.1-7.5)], as did patients on RT alone [3.9mo 95%CI(2.2-10.2)], probably because of negative selection. After RT, 106(81.5%) patients started adjuvant TMZ and received a median of 3 cycles (0-13); 28 completed ≥6 cycles. MGMT status was known in only 24/130 CCRT patients (16 unmethylated; 8 methylated), and was not significantly associated with longer survival. However, in patients receiving an alkalyting agent, mOS in methylated patients was 10.5mo [95%CI(4.0;16.4)] vs 14.3mo [95%CI(7.0;23.6)] in unmethylated patients (p = 0.399). CONCLUSIONS: Our data suggests that either standard CCRT(60Gy) or HRT could be efficiently used in patients over 70 in a non-selected GBM population. The results of ongoing prospective studies will be needed to confirm the toxicity and overall benefit.
Phase II trial of first-line gefitinib in patients unsuitable for chemotherapy with stage III/IV non-small-cell lung cancer
Authors: D. Swinson, S. Williams, K. Beddard, L. Price, L. Reaper, M. H. Cullen, D. R. Ferry
Journal: Journal of Clinical Oncology (2005)

7256 Background: The median age of patients (pts) presenting with non-small-cell lung cancer (NSCLC) is now >70 years and the role of chemotherapy in elderly pts with performance status (PS) 2 is contentious. The epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (IRESSA) was effective and well tolerated in a small study of pretreated elderly pts with NSCLC. There are few data in the first-line setting. Methods: A Phase II clinical trial enrolled chemonaïve PS 0–2 pts with NSCLC who were unfit for or declined chemotherapy. Pts received gefitinib (250 mg/day) until progression or toxicity. Response was assessed using RECIST 1 month after starting treatment and at 2-monthly intervals thereafter. Adverse events (AEs) were assessed using NCI-CTC (version 2.0). Results: 45 pts consented (unfit for/declined chemotherapy, 25/20; male/female, 29/16; median age, 76 years (range 59–85); PS 0/1/2/3, 2/15/27/1; stage III/IV, 19/26; smoking history: 19 current, 15 ex, 9 never, 2 unknown; histology: 17 squamous, 15 adenocarcinoma, 6 unclassifiable, 3 bronchioalveolar, 3 undifferentiated, 1 adenosquamous). Of these, 41 pts received gefitinib at least once and were evaluable for response and toxicity. Partial response was achieved in 4 (9.8%) pts (median duration [range], 168 [107–170] days), 15 (36.6%) had stable disease (35 [0–112] days) and 22 (53.4%) progressed. Disease control rate was 46.4% at 1 month. Median progression-free survival was 32 days and median overall survival was 82 days; 2 pts remain alive. No association was seen between response and histology, smoking history or gender. Drug-related AEs were mild: grade 2 AEs included rash (5 pts) and diarrhoea (2). Grade 3 AEs were rash (2 pts, 1 due to penicillin allergy) and diarrhoea (1). Grade 3 interstitial pneumonitis was a serious AE in 1 pt who withdrew. No other pt withdrew due to AEs. No grade 4 AEs were reported. Conclusions: Antitumour activity was observed with gefitinib 250 mg/day in this small study of chemonaïve pts (median age, 76 years; median PS 2) who were unfit for or declined chemotherapy. Further investigation of first-line gefitinib monotherapy is warranted. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca
Plasma Levels of Risk-Variant APOL1 Do Not Associate with Renal Disease in a Population-Based Cohort
Authors: Julia Kozlitina, Haihong Zhou, Patricia N. Brown, Rory J. Rohm, Yi Pan, Gulesi Ayanoglu, Xiaoyan Du, Eric Rimmer, Dermot F. Reilly, Thomas P. Roddy, Doris F. Cully, Thomas F. Vogt, Daniel Blom, Maarten Hoek
Journal: Journal of the American Society of Nephrology (2016)

Two common missense variants in APOL1 (G1 and G2) have been definitively linked to CKD in black Americans. However, not all individuals with the renal-risk genotype develop CKD, and little is known about how APOL1 variants drive disease. Given the association of APOL1 with HDL particles, which are cleared by the kidney, differences in the level or quality of mutant APOL1‑HDL particles could be causal for disease and might serve as a useful risk stratification marker. We measured plasma levels of G0 (low risk), G1, and G2 APOL1 in 3450 individuals in the Dallas Heart Study using a liquid chromatography-MS method that enabled quantitation of the different variants. Additionally, we characterized native APOL1‑HDL from donors with no or two APOL1 risk alleles by size-exclusion chromatography and analysis of immunopurified APOL1‑HDL particles. Finally, we identified genetic loci associated with plasma APOL1 levels and tested for APOL1 -dependent association with renal function. Although we replicated the previous association between APOL1 variant status and renal function in nondiabetic individuals, levels of circulating APOL1 did not associate with microalbuminuria or GFR. Furthermore, the size or known components of APOL1‑HDL did not consistently differ in subjects with the renal-risk genotype. Genetic association studies implicated variants in loci harboring haptoglobin-related protein ( HPR ), APOL1 , and ubiquitin D ( UBD ) in the regulation of plasma APOL1 levels, but these variants did not associate with renal function. Collectively, these data demonstrate that the risk of renal disease associated with APOL1 is probably not related to circulating levels of the mutant protein.
METB-09IDENTIFYING NOVEL VULNERABILITIES IN OXIDATIVE STRESS PATHWAYS IN IDH1 MUTANT GLIOMA
Authors: Fred Fack, Guillaume Hochart, Anais Oudin, William Leenders, Eyal Gottlieb, Rolf Bjerkvig, Jonathan Stauber, Simone Niclou
Journal: Neuro-Oncology (2015)

BACKGROUND: Glial tumors presenting a heterozygous point mutation in isocitrate dehydrogenase (IDH) accumulate the oncometabolite D-2-hydroxyglutarate (2-HG) leading to a hypermethylation phenotype through inhibition of α-ketoglutarate (α-KG) dependent demethylases. However the direct effect of the IDH mutation on metabolic dysregulation remains poorly understood. IDH mutant glioma cells are notoriously difficult to grow in vitro and only a handful of laboratories, including ours, have been able to generate patient derived xenograft models in vivo. Here we aimed to get insight into the major metabolic aberrations observed in human IDH mutant gliomas with a special emphasis on the energy metabolism, oxidative stress and glutamine/glutamate pathways. METHODS: In situ high resolution mass spectrometric imaging (MSI) was performed on IDH1 mutant xenograft sections derived from human oligodendroglial tumors with 1p19q deletion, providing a detailed metabolic profiling and anatomical localization in tumor sections. Key enzymes of the perturbed metabolic pathways were monitored by Western blot and immunohistochemistry. Liquid chromatography mass spectrometry (LC-MS) was applied to validate findings in clinical specimen. RESULTS: 2-HG was specifically localized in the tumor bed but not in the surrounding brain parenchyma, while α-KG levels were not significantly altered in IDH1 mutant tumors. We identified a large set of differential metabolites in IDH1-mutant tumors, including changes in lipid metabolism, in the methylation and the glutathione pathway. CONCLUSIONS: We provide a detailed metabolic mapping of human IDH mutant gliomas with high anatomical resolution in situ. Our data point to the importance of oxidative stress regulation and its possible link to epigenetic dysregulation in IDH mutant gliomas.
Unmasking the surgeons: the evidence base behind the use of facemasks in surgery
Authors: Charlie Da Zhou, Pamela Sivathondan, Ashok Handa
Journal: Journal of the Royal Society of Medicine (2015)

The use of surgical facemasks is ubiquitous in surgical practice. Facemasks have long been thought to confer protection to the patient from wound infection and contamination from the operating surgeon and other members of the surgical staff. More recently, protection of the theatre staff from patient-derived blood/bodily fluid splashes has also been offered as a reason for their continued use. In light of current NHS budget constraints and cost-cutting strategies, we examined the evidence base behind the use of surgical facemasks. Examination of the literature revealed much of the published work on the matter to be quite dated and often studies had poorly elucidated methodologies. As a result, we recommend caution in extrapolating their findings to contemporary surgical practice. However, overall there is a lack of substantial evidence to support claims that facemasks protect either patient or surgeon from infectious contamination. More rigorous contemporary research is needed to make a definitive comment on the effectiveness of surgical facemasks.
Iron overload in hereditary tyrosinemia type 1 induces liver injury through the Sp1/Tfr2/hepcidin axis
Authors: Wen-Dai Bao, Yao Fan, Yue-Zhen Deng, Ling-Yun Long, Jing-jing Wang, Dong-Xian Guan, Zhen-Yu Qian, Peng An, Yuan-Yuan Feng, Zhi-Ying He, Xiao-Fan Wang, H. Phillip Koeffler, Ronggui Hu, Jianshe Wang, Xin Wang, Fudi Wang, Jing-Jing Li, Dong Xie
Journal: Journal of Hepatology (2016)
The form and content of schizophrenic hallucinations
Authors: A R Larkin
Journal: American Journal of Psychiatry (1979)

To evaluate changes in the hallucinatory experience, the author analyzed the form and content of the hallucinations of 10 schizophrenic patients during two phases of their illness, the acute phase and remission. In both test periods the patients experienced auditory hallucinations as objectively real and as directing their thoughts and behavior. Nonauditory hallucinations appeared more common than cursory examination would suggest. The patients were able to stop auditory hallucinations during remission but not during the acute phase of their illness. Hallucinatory content was threatening and isolating during the acute phase but supportive and socially focused during remissions.
Dose reduced first-line capecitabine monotherapy in older and less fit patients with advanced colorectal cancer (ACRC)
Authors: M. C. Cripps, M. Vincent, D. Jonker, I. Kerr, B. Dingle, L. A. Martin, J. Mathews, J. Biagi, G. Knight, W. Lam
Journal: Journal of Clinical Oncology (2005)

3577 Background: Combination chemotherapy results in improved outcomes in trials of selected fit patients with ACRC. For older, less fit, more complicated patients, combination chemotherapy is associated with greater toxicity and less benefit. Sequential monotherapy is a reasonable option for these patients. Methods: A multicentre phase I/II trial of capecitabine (Xeloda) 2000mg/m2 d1–14 q21d was conducted in 214 patients in one or more of the following subsets: age≥65 years (167 pts), ECOG performance status ≥1 (139 pts), elevated LDH (105 pts), prior pelvic radiation (54 pts), liver enzyme abnormalities (5 pts). Results: Median age was 72 years (range 38 to 90). At a median follow-up of 7.2 months, 131 patients are alive. A median 4 and mean 6.5 cycles were given (range 1 to 33). Prior pelvic radiation required dose reduction to 1500mg/m2 for diarrhea in the 3rd cycle. Of 192 patients evaluable for toxicity, there were no grade 3/4 hematologic toxicities. Grade 3/4 toxicity occurred in 22% of patients during the first 3 cycles (8.9% hand-foot syndrome, 6.3% diarrhea, 2.6% lethargy, 2.6% dehydration, 1% abdominal pain, 0.5% stomatitis). Dose reductions were required in 14% and dose delays in 21% for medical reasons. Of 151 evaluable, response is 13%, with 77% disease control (CR+PR+SD). Median PFS was 5.1 months. Of 128 pts progressing, 77 (60%) received further chemotherapy. Median overall survival for all patients is 16.3 months. Median survival for ECOG PS 0, 1, and 2 are 18.4, 15.2 and 8.3 months (p=0.013 for 3 way comparison). Good prognostic factors included ECOG PS=0, LDH≤ULN, homocysteine≤ULN and history of prior pelvic RT. Conclusions: Lower dose capecitabine is tolerable and active in less fit patients. In a capecitabine registration trial with fit pts at 2500mg/m2, median survival was 12.8 months (Twelves, 2002). Although RR here was lower, survival was 16.3 months in this less fit population as part of a sequential monotherapy strategy. This study provides valuable information on outcomes in these under-studied patients for whom combination chemotherapy may not be preferred. Outcomes by subgroup will be reported at the meeting. Supported by research grant from Hoffmann-La Roche Ltd. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Ltd. Hoffmann-La Roche Ltd.
Abstract 2694: Esophageal cancer exhibits a resistance to the chemical inhibition of IGF-1R with a maintained Ras-MAPK activity
Authors: Munenori Takaoka, XiaoHong Bao, Huifang Hao, Naomasa Ishida, Takuya Fukazawa, Tomoki Yamatsuji, Minoru Haisa, Yoshio Naomoto
Journal: Cancer Research (2015)

Abstract The type 1 insulin-like growth factor receptor (IGF-1R) and its associated signaling system play a significant role in carcinogenesis and progression of gastrointestinal malignancies, and thus have provoked great interest as a promising target for cancer treatment. The aim of our study was to assess the effects of a novel IGF-1R inhibitor, NVP-AEW541, on the cell proliferation and signal transduction of esophageal squamous cell carcinoma. Five human esophageal squamous carcinoma cell lines (TE-1, TE-4, TE-8, TE-10 and T.Tn) were treated with this inhibitor and the IC50 of NVP-AEW541 for each cell line was more than 1μM, exhibiting that these cells were less sensitive to this compound. The activation of IGF-1R and AKT were dose dependently blocked by NVP-AEW541. However, the activities of the key molecules in Ras-MAPK pathway was not significantly inhibited by NVP-AEW541 without any major mutation of Ras. These results indicate that esophageal squamous cell carcinoma may be resistant to targeting IGF-IR due to its maintenance of Ras-MAPK signaling. Thus, to explore the potential mechanism of resistance will contribute to the therapeutic application for NVP-AEW541. Citation Format: Munenori Takaoka, XiaoHong Bao, Huifang Hao, Naomasa Ishida, Takuya Fukazawa, Tomoki Yamatsuji, Minoru Haisa, Yoshio Naomoto. Esophageal cancer exhibits a resistance to the chemical inhibition of IGF-1R with a maintained Ras-MAPK activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2694. doi:10.1158/1538-7445.AM2015-2694
An International Observational Study to Assess the Use of Sorafenib After Transarterial Chemoembolization (Tace) in Patients with Hepatocellular Carcinoma (Hcc): Optimis
Authors: J. Raoul, M. Peck-Radosavljevic, H.C. Lee, M. Kudo, K. Nakajima, A. Cheng
Journal: Annals of Oncology (2014)
PD-010 Erlotinib attenuates bevacizumab-mediated activation of EGFR-survival signaling in CRC models independent of KRAS status providing a rational basis for the DREAM phase III clinical trial
Authors: P. Mésange, A. Bouygues, D. Muller, A. Savina, B. Chibaudel, C. Tournigand, T. André, A. de Gramont, A. Larsen
Journal: Annals of Oncology (2015)
Molecular evolution of the mammalian ribosomal protein gene, RPS14.
Authors: D D Rhoads, D J Roufa
Journal: Molecular Biology and Evolution (1991)

Ribosomal protein S14 genes (RPS14) in eukaryotic species from protozoa to primates exhibit dramatically different intron-exon structures yet share homologous polypeptide-coding sequences. To recognize common features of RPS14 gene architectures in closely related mammalian species and to evaluate similarities in their noncoding DNA sequences, we isolated the intron-containing S14 locus from Chinese hamster ovary (CHO) cell DNA by using a PCR strategy and compared it with human RPS14. We found that rodent and primate S14 genes are composed of identical protein-coding exons interrupted by introns at four conserved DNA sites. However, the structures of corresponding CHO and human RPS14 introns differ significantly. Nonetheless, individual intron splice donor, splice acceptor, and upstream flanking motifs have been conserved within mammalian S14 homologues as well as within RPS14 gene fragments PCR amplified from other vertebrate genera (birds and bony fish). Our data indicate that noncoding, intronic DNA sequences within highly conserved, single-copy ribosomal protein genes are useful molecular landmarks for phylogenetic analysis of closely related vertebrate species.
Glucose Variability: Timing, Risk Analysis, and Relationship to Hypoglycemia in Diabetes
Authors: Boris Kovatchev, Claudio Cobelli
Journal: Diabetes Care (2016)

Glucose control, glucose variability (GV), and risk for hypoglycemia are intimately related, and it is now evident that GV is important in both the physiology and pathophysiology of diabetes. However, its quantitative assessment is complex because blood glucose (BG) fluctuations are characterized by both amplitude and timing. Additional numerical complications arise from the asymmetry of the BG scale. In this Perspective, we focus on the acute manifestations of GV, particularly on hypoglycemia, and review measures assessing the amplitude of GV from routine self-monitored BG data, as well as its timing from continuous glucose monitoring (CGM) data. With availability of CGM, the latter is not only possible but also a requirement-we can now assess rapid glucose fluctuations in real time and relate their speed and magnitude to clinically relevant outcomes. Our primary message is that diabetes control is all about optimization and balance between two key markers-frequency of hypoglycemia and HbA1c reflecting average BG and primarily driven by the extent of hyperglycemia. GV is a primary barrier to this optimization, including to automated technologies such as the "artificial pancreas." Thus, it is time to standardize GV measurement and thereby streamline the assessment of its two most important components-amplitude and timing.
Phase II Trial Of Cladribine and Low-Dose AraC (LDAC) Alternating With Decitabine In Older Patients With Acute Myeloid Leukemia (AML)
Authors: Tapan M. Kadia, Gautam Borthakur, Alessandra Ferrajoli, Preetesh Jain, Elias Jabbour, Srdan Verstovsek, Naveen Pemmaraju, Stefan Faderl, Farhad Ravandi, Marina Konopleva, Carla Tuttle, Mark Brandt, Xuemei Wang, Guillermo Garcia-Manero, Hagop M. Kantarjian, Jorge E. Cortes
Journal: Blood (2013)