tbuckley/cabot-search huggingface dataset:
MPTH-39. SEX-SPECIFIC ANALYSIS OF GBM TRANSCRIPTOMES REVEALS NEW PROGNOSTICALLY IMPORTANT MOLECULAR SUBTYPES
Authors: Wei Yang, Nicole Warrington, Jingqin Luo, Joshua Rubin
Journal: Neuro-Oncology (2016)

Molecular subtyping of GBM has advanced basic, translational and clinical neuro-oncology. As there are well-recognized sex differences in GBM incidence and outcome, we hypothesized that analysis of merged male and female datasets had previously masked important molecular features of GBM. To test this hypothesis we applied a JIVE algorithm to decompose male and female complete GBM transcriptome datasets (TCGA) accessed through the UCSC Cancer Genomics Browser, to joint and sex-specific components. We sought to determine whether there are shared or distinct GBM molecular subtypes in males and females. Using consensus hierarchical clustering independently on the sex-specific component from the JIVE, we defined five male and five female transcriptome clusters. Most clusters were a mix of samples previously assigned to the four Verhaak subtypes. While driver events were shared between the male and female clusters, they could be distinguished by their expression profiles, pathway analysis, and by their survival. Most notable were the differences between male and female subsets with the best survival. In female GBM, IDH1 mutation alone defined a single cluster with superior survival. Two male subtypes exhibited better survival, and this could not be completely explained by enrichment for IDH mutant tumors. Pathway analyses of genes differentiating a male or female cluster versus the others indicated that the male clusters with better survival were enriched with expression of collagen genes and extracellular matrix components. No similar phenotype was observed in the female subsets. The correlation between the sex-specific GBM clusters and survival was validated in further analyses of the GSE13041 and 16011 datasets. Together these data indicate that important elements of GBM biology and outcome can be discovered through sex-specific analyses and that distinctions between the biology of male and female GBM may need to be incorporated into precision approaches to treatment.
NIMG-47. MACHINE LEARNING ALGORITHMS FOR PREDICTING GBM GROWTH PATTERNS USING ADVANCED AND DELAYED-CONTRAST MRI: FEASIBILITY DEMONSTRATION
Authors: David Guez, David Last, Dianne Daniels, Dvora Nass, Sharona Salomon, Alisa Talianski, Andrew Kanner, Deborah T. Blumenthal, Felix Bokstein, Dror Limon, Tzahala Tzuk, Zvi Cohen, Leor Zach, Yael Mardor
Journal: Neuro-Oncology (2016)

We have recently presented delayed-contrast-MRI-based treatment response assessment maps (TRAMs) enabling efficient separation between tumor and treatment-effects, validated histologically in 54 resected patients, reaching 100%/93% sensitivity/PPV to active tumor. Here we demonstrate potential prediction of tumor growth patterns using a neural network (NN) and advanced-MRI including the TRAMs. GBM patients were followed by advanced-MRI (T1-Gd, diffusion, perfusion, T2, FLAIR, TRAMs) acquired every 2 months during periods of no treatment changes. Each patient underwent 2-9 consecutive MRI follow-ups. All MRIs were co-registered. Regions-of-interest (ROIs) were plotted surrounding enhancing regions on T1-Gd and copied to all the patients’ MRIs/maps. Then all pixels within these ROIs were fed into the NN. The NN was then trained to use all the pixels of the various MRI sequences acquired during one MRI exam to predict the tumor spatial distribution (calculated from the TRAMs) of the following MRI exam. Data of 6 patients (2.6x106 pixels from 22 follow-ups) were used to train the NN and data of additional 3 patients (0.65x106pixels from 10 follow-ups) served as the test group. The NN was fed with the multi-dimensional data of each pixel individually and with micro-environmental information consisting of local tumor density per-pixel and the distance to the tumor edge per-pixel, calculated from the TRAMs. 8% of the tumor pixels in the outcome TRAMs were correctly predicted by the NN for the test group. ROC analysis resulted in AUC=0.70, sensitivity=71%, specificity=58% and F1-score=77%. These preliminary results demonstrate the potential of this per-pixel based machine learning algorithm to predict GBM growth patterns. The TRAMs high sensitivity/PPV to active tumor provides the essential deterministic definition of input and outcome for the algorithm. The reliability of such a NN for potential clinical application is yet to be studied in a significantly larger group of patients.
Management of hepatitis C positive patients undergoing active treatment for malignancies: a position paper from the Associazione Italiana di Oncologia Medica (AIOM) and the Società Italiana di Malattie Infettive e Tropicali (SIMIT)
Authors: P. Pedrazzoli, V. Zuccaro, A. Pagani, M. Puoti, G.B. Gaeta, C. Pinto, G. Taliani, F. Baldanti, S. Cinieri, R. Bruno
Journal: Annals of Oncology (2016)
Induction Mortality In Pediatric Acute Lymphoblastic Leukemia (ALL): a Retrospective Cohort Analysis From the Pediatric Health Systems Information (PHIS) Database, 1999–2009
Authors: Alix E. Seif, Susan R. Rheingold, Brian T. Fisher, Yuan-Shung V. Huang, Yimei Li, Leslie S. Kersun, L. Charles Bailey, Anne F. Reilly, Richard Aplenc
Journal: Blood (2010)
The Epigenetic Effect of Phenylhexyl Isothiocyanate on Histone Acetylation in Patients with Acute Leukemia and Non-Leukemic Disorders.
Authors: Liyun Xiao, Xudong Ma, Yiqun Huang, Ruiji Zhen, Xiaoling Ye, Jen-Wei Chiao, Delong Liu
Journal: Blood (2007)
Hypoglycemia
Authors: Amy E. Thompson
Journal: JAMA (2015)

HypoglycemiaHypoglycemia (low blood sugar) is a sign of a problem; it is not a disease itself.The brain and other tissues in the body use glucose, or sugar, as fuel.You get most of the glucose your body needs from your diet.The liver and kidneys are able to make glucose when necessary.Excess glucose is stored as glycogen (many glucose molecules linked together) in the liver and in muscle.Tell your doctor if you have frequent or recurring episodes of hypoglycemia because this may indicate an underlying health problem.
Tandem repeat variation in HIC1 gene predicts outcome for oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer
Authors: S. Okazaki, F. Loupakis, M. Schirripa, S. Cao, W. Zhang, D. Yang, Y. Ning, M.D. Berger, Y. Miyamoto, M. Suenaga, R. Gopez, B.B. Borelli, C. Cremolini, A. Falcone, S. Lonardi, L. Salvatore, H. Uetake, T. Kawano, T. Helentjaris, H.-J. Lenz
Journal: Annals of Oncology (2016)
HER2 targeting therapy for advanced gastric cancer
Authors: Kohei Shitara
Journal: Annals of Oncology (2016)

In recent years, various molecular target agents have been investigated for advanced gastric cancer (AGC). Main targets are receptor tyrosine kinase, angiogenesis system and intracellular signaling system. The anti-HER2 antibody trastuzumab was shown to prolong the overall survival (OS) of patients with HER2+ AGC, and now become one of the standard treatments. In contrast, lapatinib, an anti-HER2 or EGFR tyrosine kinase inhibitor, could not show sufficient improvement of OS in first-line (LOGiC) or second-line (TyTAN) for HER2+ AGC. Furthermore, ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate (ADC) for HER2 could not show superior efficacy in comparison with taxanes agents as second-line for AGC (GATSBY), although it already showed remarkable efficacy for HER2+ breast cancer. These negative trials for HER2+ AGC clearly indicated that different treatment strategies is required, which include identification of patient's status timely manner, patient's refinement by additional biomarker, evaluation of impact of intra-tumor heterogeneity and understanding of resistance mechanism as well as optimal combination.
Prognostic and predictive significance of VEGF and TNF&amp;agr; levels in ascites of patients with epithelial ovarian cancer. Correlation with lymphocytes subpopulations
Authors: M. Liontos, N. Gavalas, K. Tzanis, S.-P. Trachana, E. Kostouros, F. Zagouri, K. Koutsoukos, M. Lykka, G. Tsironis, I. Dimitriadis, E. Terpos, M. Dimopoulos, A. Bamias
Journal: Annals of Oncology (2016)
Serum interleukin-6 as a prognostic biomarker for survival in patients with unresectable pancreatic cancer
Authors: I. Chen, C. Dehlendorff, B.V. Jensen, P. Pfeiffer, S.E. Nielsen, N.H. Holländer, M.K. Yilmaz, J. Johansen
Journal: Annals of Oncology (2016)
Durable Engraftment and Long-Term Survival Following Fludarabine-Based Nonmyeloablative Hematopoietic Cell Transplantation (HCT) in Patients with ATG-Refractory Severe Aplastic Anemia (SAA) and Other Nonmalignant Hematological Disorders.
Authors: Sakti Chakrabarti, Y. Takahashi, R. Srinivasan, I. Espinoza, T. Igarashi, D. Suffredini, M. Marquesen, R. A. Shalabi, C. D. Bolan, S. F. Leitman, A. J. Barrett, N. S. Young, R. Childs
Journal: Blood (2004)
Soluble Recombinant Thrombomodulin Is a Potentially Promising Agent without Causing Severe Hemorrhagic Events for Hematological Malignancy-Induced Disseminated Intravascular Coagulation
Authors: Naoki Kurita, Hidekazu Nishikii, Yasuhisa Yokoyama, Mamiko Sakata-Yanagimoto, Naoshi Obara, Yasushi Okoshi, Kazumi Suzukawa, Yuichi Hasegawa, Shigeru Chiba
Journal: Blood (2012)
Early Recovery of Thymus-Derived Naïve T Cells in Pediatric Patients (pts) Treated with Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation (NMSCT) for Cancer.
Authors: Terry J. Fry, Alison R. Rager, Frances Hakim, Cynthia Love, Paula Layton, Daniel Fowler, Michael R. Bishop, Ronald Gress, Crystal L. Mackall, Alan S. Wayne
Journal: Blood (2006)
Mcl-1 Degradation Is Required for Targeted Therapeutics to Eradicate Colon Cancer Cells
Authors: Jingshan Tong, Peng Wang, Shuai Tan, Dongshi Chen, Zaneta Nikolovska-Coleska, Fangdong Zou, Jian Yu, Lin Zhang
Journal: Cancer Research (2017)

Abstract The Bcl-2 family protein Mcl-1 is often degraded in cancer cells subjected to effective therapeutic treatment, and defective Mcl-1 degradation has been associated with intrinsic and acquired drug resistance. However, a causal relationship between Mcl-1 degradation and anticancer drug responses has not been directly established, especially in solid tumor cells where Mcl-1 inhibition alone is insufficient to trigger cell death. In this study, we present evidence that Mcl-1 participates directly in determining effective therapeutic responses in colon cancer cells. In this setting, Mcl-1 degradation was induced by a variety of multikinase inhibitor drugs, where it relied upon GSK3β phosphorylation and FBW7-dependent ubiquitination. Specific blockade by genetic knock-in (KI) abolished apoptotic responses and conferred resistance to kinase inhibitors. Mcl-1-KI also suppressed the antiangiogenic and anti-hypoxic effects of kinase inhibitors in the tumor microenvironment. Interestingly, these same inhibitors also induced the BH3-only Bcl-2 family protein PUMA, which is required for apoptosis. Degradation-resistant Mcl-1 bound and sequestered PUMA from other prosurvival proteins to maintain cell survival, which was abolished by small-molecule Mcl-1 inhibitors. Our findings establish a pivotal role for Mcl-1 degradation in the response of colon cancer cells to targeted therapeutics, and they provide a useful rational platform to develop Mcl-1–targeting agents that can overcome drug resistance. Cancer Res; 77(9); 2512–21. ©2017 AACR.
Use of DPC-4 immunostaining of diagnostic cytology specimens to predict the pattern of tumor progression in locally advanced pancreatic cancer patients (LAPC).
Authors: C. H. Crane, J. S. Yordy, G. R. Varadhachary, W. Haque, R. A. Wolff, P. Das, S. Krishnan, J. B. Fleming, J. L. Abbruzzese, G. A. Staerkel
Journal: Journal of Clinical Oncology (2011)

209 Background: An autopsy study has identified DPC-4 as a potential biomarker of the pattern of disease spread in pancreatic cancer patients (Iacobuzio-Donahue et al, JCO, 2009). We sought to determine whether DPC-4 expression determined by immunohistochemistry (IHC) staining of primary tumor cytology specimens correlates with the clinical pattern of progression in patients with locally advanced pancreatic cancer (LAPC). Methods: LAPC patients with ECOG 0-1 PS were treated with gemcitabine (1000 mg/m 2 ), oxaliplatin (100 mg/m 2 ), and cetuximab for (500mg/m 2 ) q2wks for 4 doses followed by XRT (50.4 Gy to the gross tumor only) with capecitabine (825 mg/m 2 twice daily, days of radiation) and cetuximab on a multiinstitutional trial. Forty-one of 58 patients treated at our institution had cytology specimens suitable for IHC staining. The patterns of progression were determined based on radiographic studies and clinical symptoms. Findings were blinded from the IHC results. Patients were categorized as 1) local disease dominant, 2) distant disease dominant, 3) indeterminate pattern, and 4) no progression. The IHC scoring of DPC-4 was determined by an experienced cytopathologist who was blinded from the clinical data. Results: Median, 1yr and 3yr actuarial OS are 18.2 months, 67.2% and 18.5%. Dominant progression pattern was local (n=15), distant (n=14), indeterminate (n=8), and no progression (n=4). Intact DPC expression correlated with local dominant progression (11/15) and DPC-4 loss correlated with distant dominant progression (10/14), p=0.016. The median DM free survival rate was 18.0 for intact DPC-4 versus 12.5 mo for DPC-4 loss patients (p=NS). There was no significant difference in overall survival based on DPC-4 status. Conclusions: Determination of DPC-4 expression from cytology specimens is feasible. DPC-4 expression correlated with the pattern of progression and is consistent with previous autopsy data. DPC-4 expression does not appear to be predictive or prognostic. Prospective validation of DPC-4 as a biomarker of disease progression is warranted and may lead to personalized treatment strategies for patients with LAPC. [Table: see text]
Vitamin D and Depression: Cellular and Regulatory Mechanisms
Authors: Michael J. Berridge
Journal: Pharmacological Reviews (2017)

Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca<sup>2+</sup> within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP<sub>3</sub>) that releases Ca<sup>2+</sup> from the internal stores. The importance of these two pathways in driving the elevation of Ca<sup>2+</sup> is supported by the fact that depression can be alleviated by ketamine that inhibits the NMDARs and scopolamine that inhibits the M1 receptors that drive InsP<sub>3</sub>/Ca<sup>2+</sup> pathway. This increase in Ca<sup>2+</sup> not only contributes to depression but it may also explain why individuals with depression have a strong likelihood of developing Alzheimer's disease. The enhanced levels of Ca<sup>2+</sup> may stimulate the formation of A<i>β</i> to initiate the onset and progression of Alzheimer9s disease. Just how vitamin D acts to reduce depression is unclear. The phenotypic stability hypothesis argues that vitamin D acts by reducing the increased neuronal levels of Ca<sup>2+</sup> that are driving depression. This action of vitamin D depends on its function to maintain the expression of the Ca<sup>2+</sup> pumps and buffers that reduce Ca<sup>2+</sup> levels, which may explain how it acts to reduce the onset of depression.
Five-Year Outcomes of a Randomized Trial of Gastric Band Surgery in Overweight but Not Obese People With Type 2 Diabetes
Authors: John M. Wentworth, Paul Burton, Cheryl Laurie, Wendy A. Brown, Paul E. O’Brien
Journal: Diabetes Care (2017)

The incremental benefit of bariatric surgery in people who receive good diabetes care is uncertain. So far only one randomized trial of surgery for obese people with type 2 diabetes (T2D) has reported 5-year outcomes. Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) reduced the burden of glucose-lowering medication and delivered diabetes remission in 50% of surgical-arm participants (1). We previously reported 2-year outcomes of a randomized trial of laparoscopic adjustable gastric band (GB) surgery in overweight but not obese Australians with T2D of less than 5 years’ duration (2). Diabetes remission, defined as fasting glucose <7.0 and 2-h glucose <11.1 mmol/L after a 75-g oral challenge, was observed in 52% of GB participants. The protocol, methods, and extended data are available in the Supplementary Data online.

We now report 5-year outcomes. Of 51 participants who enrolled in the study between 2009 and 2011, 45 (22 randomized to receive GB combined with medical care and 23 to medical care alone [MED]) were followed to 5 years. The mean ± SD weight loss (WL) at the end of the study was 11.2 ± 7.6% and 2.6 ± 6.9% of baseline in GB and MED participants, respectively (difference 8.6%, 95% CI 4.2–13.0). The average WL over the 5 years of the study was 12.2% in GB and 1.8% in MED participants (difference 10.4%, 95% CI 6.9–13.8) (Fig. 1 A ). This degree of incremental WL was lower than that seen in the prior surgical study in obese people …
RTHP-26. EVALUATING A SINGLE ISOCENTER RADIATION APPROACH TO TREAT MULTIPLE BRAIN METASTASES (BM) WITH STEREOTACTIC RADIOSURGERY (SRS): IMPACT OF LESION NUMBER, LOCATION AND VOLUME ON TREATMENT PLAN RESULTS
Authors: Andrew A. Kanner, Benjamin W. Corn
Journal: Neuro-Oncology (2016)

In an attempt to diminution the sequelae of whole brain irradiation, multiple BM are more frequently approached with SRS rather than whole brain irradiation. However, the individual treatment of each lesion with a multi-isocenter, serial approach is cumbersome and time consuming. We elected to investigate a single-isocenter volumetric modulated arc therapy (VMAT) planning and treatment technique for radiosurgical treatment of multiple BM. The emphasize was placed on tumor number, size, volume and location and its impact on the treatment plan. Treatment plan data of 10 patients with multiple BM were selected for a prospective comparative study investigating single-isocenter arc-based VMAT or multiple static beam approach, treating in parallel, using manual weighting to compensate for different dose and target volume. Arcs or static beams were planned for simultaneous irradiation of multiple targets to maximize beam on-time efficiency. To accommodate varying dose prescriptions, selected arcs were re-irradiated for dose escalation. Beam weights were adjusted until all prescription constraints were encountered. For comparative purposes, VMAT plans were generated utilizing an established single-isocenter, 3-5 arc planning template. All plans were compared by means of Paddick conformity index, Radiation Therapy Oncology Group Conformity Index, gradient index, and the normal brain volume receiving 12Gy. Monitor units and delivery time (evaluation with Mobius3d) were charted for each plan. Detailed results will be presented at the meeting. VMAT plans with varying dose prescriptions for multiple BM, had comparable dosimetric coverage as static beam plans for regular and more complex shapes, but were obtained with faster delivery time. For irregular and very long/narrow target shapes, VMAT optimization process might be of advantage, probably due to the optimization process during inverse planning. The use of static beams is more demanding, nevertheless can yield comparable efficient dose distribution, though with lower overall monitor units.
ANNOUNCE 2: An open-label phase 1b, and a randomized, double-blind phase 2 study of olaratumab with gemcitabine plus docetaxel in the treatment of patients with advanced soft tissue sarcoma (STS)
Authors: A. Redondo, C. Valverde Morales, N. Hindi, J.A. Lopez-Martin, G. Honigschmidt, Y. Zeng, J. Chen, D.F. Tai, G. Mo, R. Ilaria, N.S. Pillay, N. Drove, M. Jamarik
Journal: Annals of Oncology (2016)
Highlighting differences in education satisfaction and professional development between medical and clinical oncologists in Europe. A European survey conducted by the Hellenic Group of Young Oncologists (HeGYO)
Authors: E. Aravantinou Fatorou, G. Papaxoinis, K. Kamposioras, A. Korogiannos, V. Papadopoulos, G. Lazaridis, M. Nikolaou, E. Voulgaris, E. Bournakis, K. Tsigaridas, M. Liontos, E. Pantavou, N. Chatzifoti, P. Zaxaropoulou, I. Varthalitis, A. Athanasiadis, N.G. Tsoukalas
Journal: Annals of Oncology (2016)
Hypomethylating Agent Therapy and Survival Among Older Patients with Chronic Myelomonocytic Leukemia in the United States: A Large Population-Based Study
Authors: Amer M. Zeidan, Xin Hu, Jessica B. Long, Rong Wang, Scott F Huntington, Nikolai A Podoltsev, Steven Gore, Xiaomei Ma, Amy J. Davidoff
Journal: Blood (2016)
Peripheral Immune Profile and Minimal Residual Disease (MRD) Burden Following Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM)
Authors: David Foureau, Qing Zhang, Tammy D Cogdill, Adina S Wynn, Nury M. Steuerwald, Lawrence J. Druhan, Fei Guo, Katherine Rigby, Kyle L Madden, James T Symanowski, Belinda R. Avalos, Edward A. Copelan, Saad Z Usmani, Manisha Bhutani
Journal: Blood (2016)
P07.08 Higher functional hub load at diagnosis is associated with shorter survival in glioma patients
Authors: J. Derks, A. Dirkson, P. C. De Witt Hamer, Q. Van Geest, H. E. Hulst, F. Barkhof, P. J. W. Pouwels, J. J. G. Geurts, J. C. Reijneveld, L. Douw
Journal: Neuro-Oncology (2016)
GENT-36. THE GENOMIC LANDSCAPE OF SCHWANNOMA
Authors: Sameer Agnihotri, Mark Wilson, Shahrzad Jalali, Arnavaz Danesh, Mira Li, George Klironomos, Jonathan Krieger, Alireza Mansouri, Osaama Khan, Mamatjan Yasin, Peter Tonge, Pankaj Kumar Agarwalla, Wenya Linda Bi, Ian Dunn, Rameen Beroukhim, Michael Fehlings, Vera Bril, Stefano Pagnotta, Trevor Pugh, Antonio Iavarone, Kenneth D. Aldape, Gelareh Zadeh
Journal: Neuro-Oncology (2016)

Schwannomas are common cranial and spinal nerve tumors that can cause significant debilitating morbidities. To date, clinical trials for schwannomas have yielded mixed to no benefits and this may be in part due to a lack of fully understanding the somatic alterations that occur in schwannoma. We performed an integrative multiplatform analysis to determine the genomic landscape of sporadic schwannomas. Exome sequence analysis with validation by targeted DNA-sequencing of 125 samples uncovered, in addition to expected NF2 disruption, recurrent mutations in ARID1A, ARID1B and DDR1. Genome wide methylation profiling revealed that schwannomas consists of two molecular subgroups with unique gene signatures and anatomical location. RNA sequencing revealed a recurrent in-frame gene fusion on chromosome 10q in 12/125 (10%) cases, and genomic analysis identified the mechanism to be from a balanced 19Mb chromosomal inversion. The presence of the fusion was associated with male gender predominance, occurring in one out of every six men with schwannoma. Expression of the fusion transcript in both schwannomas and normal schwann cells resulted in elevated phosphorylated-ERK, increased proliferation, increased invasion and resulted in the formation of in vivo xenografts. Targeting of the MEK/ERK pathway was effective in fusion-positive Schwann cells, suggesting a possible therapeutic approach for this subset of tumors. Our study provides rationale that integrative analysis approaches can identify novel therapies for schwannoma patients.