tbuckley/cabot-search huggingface dataset:
MPTH-53. COMPREHENSIVE SURVIVAL ANALYSIS OF MGMT PROTEIN EXPRESSION BY TRADITIONAL AND QUANTITATIVE FLUORESCENCE IMMUNOHISTOCHEMISTRY COMPARED TO MGMT PROMOTER METHYLATION IN A LARGE INSTITUTIONAL GLIOBLASTOMA COHORT TREATED WITH THE STUPP PROTOCOL
Authors: Aline Paixao Becker, Erica H. Bell, Joseph P. McElroy, Tiantian Cui, Marjolein Geurts, Jessica Fleming, Arup Chakraborty, Ziyan Liu, Pierre Robe, Arnab Chakravarti
Journal: Neuro-Oncology (2016)

PCR-based methods are the gold standard to assess MGMT methylation status, which predicts the response to treatment with the alkylating agent temozolomide plus radiation therapy (Stupp protocol). Our previous studies suggest that immunohistochemistry (IHC) is a reliable method to detect MGMT status. Herein, we aim to compare the correlation of MGMT methylation and protein expression, through traditional (T-IHC) and quantitative-fluorescence IHC (AQUA), with overall survival of patients with GBM and in their response to Stupp protocol. FFPE samples from 533 primary and recurrent GBMs were analyzed. Methylation, T-IHC and AQUA data were available for 227, 493 and 501 samples, respectively. MGMT promoter methylation status was calculated from Illumina HM-450K data with the MGMT-STP27 model. OS was compared between MGMT methylated and unmethylated and positive and negative for MGMT nuclear expression (cutoff=15%) groups. For AQUA values (continuous variable), we used COX regression to calculate the hazard ratio. We further stratified the cases according to treatment (Stupp protocol, monotherapy, or no adjuvant treatment). Statistical tests were performed with SPSS. In the univariate analysis of the whole series, difference in overall survival was significant for MGMT methylation (p=0.001) and MGMT protein expression (AQUA) (95% CI: 1.000-1.002; p=0.025), but not for MGMT protein expression (T-IHC) (p=0.105). Stratification identified significant longer OS in response to Stupp protocol with methylation (p=0.005), T-IHC (p=0.006) and AQUA (p=0.002) data. Our results confirm the potential of MGMT as a prognostic biomarker and show that MGMT protein expression can also be a significant surrogate of MGMT function. The use of IHC to detect MGMT status, increases access and reduces costs to routine pathological labs to identify a subset of GBMs with better response to treatment. FUNDING: R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).
IMST-26. TUMOR TREATING FIELDS EXPOSURE OF TUMOR CELLS INDUCE ACTIVATION PHENOTYPE IN IMMUNE CELLS
Authors: Talia Holtzman
Journal: Neuro-Oncology (2016)

Therapeutic low dose alternating electric fields (TTFields) appear to act by disrupting cells in mitosis, leading to aberrant mitotic exit. Such mitotic catastrophe has been shown to induce immunogenic cell death programs that initiate the recognition and destruction of cells and drive pro-inflammatory cytotoxic responses against these cells. We have previously reported that TTFields-treated patients receiving dexamethasone above a threshold dose of 4.1 mg/day had significantly poorer outcomes compared to patients receiving lower doses. These data suggest the potential requirement for an immune response within the TTFields mechanism of action. Here we show here that cells exposed to TTFields exhibit evidence of endoplasmic reticulum stress, surface expression of immune stimulatory stress marker proteins calreticulin, and the secretion of the Alarmin/DAMP protein, HMGB1. Co-culture of bone marrow derived macrophages with TTFields-treated CT26 cells resulted in the up-regulation of cell surface activation markers that was reversed by the addition of anti-HMGB1 antibodies. These data begin to provide a molecular basis for immunologic involvement in TTFields-based therapies and may provide the basis for future clinical guidance to improve treatment efficacy.
Fate of the C3H Milk Influence in Mice of Strains C and C57 Black
Authors: Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1945)

Journal Article Fate of the C3H Milk Influence in Mice of Strains C and C57 Black Get access Howard B. Andervont Howard B. Andervont Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 6, June 1945, Pages 383–390, https://doi.org/10.1093/jnci/5.6.383 Published: 01 June 1945
METB-08. INCREASING GLUCOSE CONCENTRATIONS IS DELETERIOUS TO Th1 AND CYTOTOXIC T CELLS
Authors: Amber Giles
Journal: Neuro-Oncology (2016)

Hyperglycemia has been associated with shorter survival in patients with newly diagnosed glioblastoma(GBM), even after controlling their glucocorticoid levels. Prior studies have defined the specific metabolic pathways that are linked with the fate of T cells. As a consequence, altering the T-cell’s metabolism can increase the efficiency of the T-cell function in certain nutrient niche. Glucose, glutamine and fatty acids are the main nutrients that support T cell bioenergetics and biosynthesis. We hypothesized that the immune system in GBM is differentially affected by the availability of specific nutrients. This is supported by recent data from squamous cell carcinoma where studies showed that upregulation of glycolysis correlated inversely with CD8+ T cell infiltration and survival. To investigate the link between hyperglycemia and poor survival rates in GBMs, we have initiated a detailed metabolic study of various functional T cell subsets generated in the presence of different media conditions. CD4+ and CD8+ T cells were grown in media that contained the following nutrients: 0 g/L glucose/4 mM glutamine; 1 g/L glucose/4mM glutamine; 2g/L glucose/4mM glutamine; 1 g/L glucose/0mM glutamine; 2g/L glucose/0 mM glutamine. Healthy donor T cells were cultured in these varying media under non-stimulatory, anti-CD3/anti-CD28 stimulatory, or Th1 polarizing conditions. Specific T cell lineages and absolute number were quantified using flow cytometry. Our preliminary results show that glutamine is essential for T-cell viability in any state. Surprisingly, high concentrations of glucose (2g/L and 1g/L) are deleterious to Th1 polarized CD4+ and CD8+ T-cells but do not affect the viability of the unstimulated or stimulated T-cells. These results suggest that T cells in different states have varied preferences for different carbon sources and associated metabolic pathways. Further, these studies support continued investigation of strategies to alter metabolic pathways in order to increase the efficiency of immune therapies.
Long-term outcomes with nivolumab (Nivo) vs docetaxel (Doc) in patients (Pts) with advanced (Adv) NSCLC: CheckMate 017 and CheckMate 057 2-y update
Authors: F. Barlesi, M. Steins, L. Horn, N. Ready, E. Felip, H. Borghaei, D.R. Spigel, O. Arrieta, S.J. Antonia, J. Fayette, N. Rizvi, L. Crinò, M. Reck, W.E. Eberhardt, M. Hellmann, W.J. Geese, A. Li, D. Healey, J.R. Brahmer, L. Paz-Ares
Journal: Annals of Oncology (2016)
The Preclinical Efficacy of a Novel Telomerase Inhibitor, Imetelstat, in AML - a Randomized Trial in Patient-Derived Xenografts
Authors: Claudia Bruedigam, Brad Wackrow, Axia Song, Amy H Porter, Stanley Chun-Wei Lee, Andrew S. Moore, Omar Abdel-Wahab, Steven W Lane
Journal: Blood (2016)
Clinical Relevance of Circulating Myeloperoxidase (MPO) in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS).
Authors: Iman Jilani, Ted Vincenti, Homan Faraji, Francis J. Giles, Elihu Estey, Hagop M. Kantarjian, Maher Albitar
Journal: Blood (2004)
Famosa: Evaluation of a multigene panel in patients with suspected HBOC
Authors: E. Adrover, I. Esteban, G. Llort, S. Servitja, S. Martinez Peralta, I. Garau, J.M. Cano, R. Serrano, M.J. Juan Fita, A. Casas, B. Graña, A. Teulé, A. Marquez, J.E. Ales Martínez, A. Antón, J. Brunet, F. Balaguer, S. Gonzalez, J. Balmaña, C. Alonso
Journal: Annals of Oncology (2016)
Prognostic mRNA expression signatures in whole blood in patients with metastatic colorectal cancer treated with 3rd line cetuximab and irinotecan
Authors: J.V. Schou, B.V. Jensen, D.L. Nielsen, J.A. Palshof, E. Høgdall, M.K. Yilmaz, P. Pfeiffer, J. Johansen, S. Rossi
Journal: Annals of Oncology (2016)
What is “Epithelium”?: Reply
Authors: Yoji Ikawa
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article What is “Epithelium”?: Reply Get access Yoji Ikawa, M.D. Yoji Ikawa, M.D. National Cancer Institute, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 6, June 1973, Pages 1727–1728, https://doi.org/10.1093/jnci/50.6.1727-a Published: 01 June 1973
Prognostic Role of Serum Albumin Level in DLBCL before and during the Rituximab Era. Retrospective GISL Study over 738 Cases
Authors: Luigi Marcheselli, Alessia Bari, Samantha Pozzi, Raffaella Marcheselli, Maria Christina Cox, Luca Baldini, Stefano Luminari, Stefano Sacchi
Journal: Blood (2014)
Predictive Factors of All Trans-Retinoic Acid (ATRA) Related Complications during Induction Course of Acute Promyelocytic Leukemia (APL).
Authors: Jeddi Ramzi, Kacem Karima, Benneji Hend, Mnif Samia, Belakhal Raihane, Aissaoui Lamia, Benabid Hela, Belhadjali Zaher, Meddeb Balkis
Journal: Blood (2006)
Interleukin-15 Upregulates the Expression of NK-Cell Activating Receptors and Concomitantly Increases the NK Cytotoxicity in Patients with Acute Myeloid Leukemia.
Authors: Miroslaw J. Szczepanski, Malgorzata Czystowska, Marta Szajnik, Ann Welsh, Kenneth A. Foon, Theresa L. Whiteside, Michael Boyiadzis
Journal: Blood (2007)
Use of Oncotype DX Recurrence Score® (RS) reduces chemotherapy (CT) beyond treatment decisions using Ki67-based determinations of luminal A and B breast cancer subtypes: a retrospective study in the Spanish population
Authors: L. Garcia-Estevez, E. Hernandez, D. Acosta, F. Lopez-Rios, M. Prieto Pozuelo, I. Calvo
Journal: Annals of Oncology (2016)
EXTH-30. TUMOR TREATING FIELDS (TTFIELDS) INDUCE AUTOPHAGY IN GLIOMA CELLS
Authors: Yaara Porat, Anna Shteingauz, Moshe Giladi, Rosa Schneiderman, Tali Voloshin, Mijal Munster, Roni Blat, Eilon Kirson, Uri Weinberg, Yoram Palti
Journal: Neuro-Oncology (2016)

Tumor treating fields (TTFields) are an established anti-neoplastic treatment modality in patients with glioblastoma. TTFields are delivered via noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to the region of the tumor. Previous studies have shown that TTFields lead to increased granularity which is often associated with autophagy. Autophagy has been shown to regulate cell survival and proliferation under stress conditions and to influence cellular response to cytotoxic drugs. The goal of this study was to evaluate the possible effect of TTFields on the induction of autophagy in glioma cells. Different glioma cell lines were treated with TTFields using the inovitro system. Cellular granularity was evaluated using flow cytometry. Autophagy was monitored by quantifying levels of lipidated Microtubule Associated Protein Light Chain 3 (LC3-II) using immunoblotting and immunofluorescence microscopy. Transmission Electron Microscopy (TEM) was used to visualize autophagosome-like structures. Flow cytometry analysis demonstrated that TTFields application leads to a significant increase in cellular granularity in all tested cell lines. Significant elevation in LC3-II levels was observed in treated U-87 MG cells using immunoblotting analysis. Evidence of increased autophagy following TTFields application was also detected using fluorescence microscopy, where punctate distribution of LC3-II was observed. TEM micrographs demonstrated the presence of autophagy typical, autophagosome-like structures in TTFields treated cells. Combination of TTFields with chloroquine, an autophagy inhibitor, resulted in a significant dose dependent reduction of cell growth compared with TTFields treatment alone. TTFields are known to exert anti-mitotic effects by disrupting highly dipolar structures which play critical roles in mitosis. Our results suggest that in addition, TTFields can also induce cellular autophagy. Importantly, inhibition of autophagy sensitizes tumor cells to TTFields treatment. Future studies are warranted to examine to what extent TTFields-elicited- autophagy may affect treatment outcomes, and to investigate the therapeutic implications of combining TTFields with autophagy inhibitors in vivo.
Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer
Authors: Yuli Wang, Pengju Zhang, Yunshan Wang, Panpan Zhan, Chunyan Liu, Jian-Hua Mao, Guangwei Wei
Journal: Cancer Research (2017)

Abstract The ErbB3 receptor–binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function. In contrast, EBP1 P42 bound to both the F-box domain of FBXW7 as well as FBXW7 substrates. This adapter function of EBP1 P42 stabilized the interaction of FBXW7 with its substrates and promoted FBXW7-mediated degradation of oncogenic targets, enhancing its overall tumor-suppressing function. Overall, our results establish distinct physical and functional interactions between FBXW7 and EBP1 isoforms, which yield their mechanistically unique isoform-specific functions of EBP1 in cancer. Cancer Res; 77(8); 1983–96. ©2017 AACR.
Late Relapses Following All-Trans Retinoic Acid for Acute Promyelocytic Leukemia Are Uncommon, Respond Well to Salvage Therapy and Occur Independently of Prognostic Factors At Diagnosis: Long-Term Follow-up of North American Intergroup Study I0129
Authors: Dan Douer, Lynette Zickl, Charles A. Schiffer, Frederick R. Appelbaum, James H. Feusner, Lois E Shepherd, Cheryl L Willman, Clara D. Bloomfield, Jacob M. Rowe, Peter H. Wiernik, Martin S. Tallman
Journal: Blood (2011)
NCOG-14. WHITE MATTER CHANGES LINKED TO LANGUAGE RECOVERY IN ADULT GLIOMA
Authors: David Altshuler, Lin Wang
Journal: Neuro-Oncology (2016)

CNS neoplasms are a major cause of morbidity and mortality in the US. Current treatments focus on enhancing survival, however >70% of patients experience language, motor, or cognitive dysfunction resulting in impaired quality of life. Little is known about the mechanisms of CNS plasticity and the effect on language impairment and recovery in glioma patients. We are studying the influence of a polymorphism in the brain derived neurotrophic factor (BDNF) gene on these processes. A BDNF val66met genotype “low performance allele”(LPA) results in diminished BDNF secretion compared to the more prevalent val/val genotype “high performance allele”(HPA). The objective of this study is to characterize the influence of this polymorphism on white matter integrity and functional language outcomes in patients with glioma. 87 adult patients were included in the study. Subjects underwent longitudinal language assessments, tissue immunohistochemistry, DTI MRI, BDNF genotyping, and plasma BDNF quantification. The HPA genotype represented 77% of the study population while the LPA genotype represented 23%, replicating prevalence in the general population. ELISA confirmed elevated plasma BDNF in the HPA population (1160.31 pg/ml vs. 395.5 pg/ml,p=0.05). Peritumor myelinogensis markers GAP43, CNPase, and O4 were diminished in the LPA population by immunohistochemistry and western blot (p<0.05). DTI revealed decreased integrity of the superior longitudinal fasciculus, an important language tract in the LPA population compared to HPA and control. A greater percentage of LPA patients were severely aphasic both pre and post-operatively by Boston Diagnostic Aphasia Examination score (P<0.05). The results demonstrate the significance of BDNF on language function in adult glioma patients. BDNF polymorphisms are implicated in white matter repair processes by plasma level, tissue expression, DTI, and functional language outcomes. Targeting BDNF and the mechanisms underlying white matter repair may lead to improved quality of life and functional recovery in patients with glioma.
Eribulin mesylate may improve the sensitivity of endocrine therapy in metastatic breast cancer
Authors: K. Kobayashi, Y. Ito, T. Shibayama, I. Fukada, N. Ishizuka, R. Horii, S. Takahashi, F. Akiyama, T. Iwase, S. Ohno
Journal: Annals of Oncology (2016)
Different Proliferative Potential and Redistribution Kinetics of Human Cord Blood-Derived CD34- SCID-Repopulating Cells (SRCs) in Comarison with CD34+CD38+/− SRCs Using Intra-Bone Marrow Injection.
Authors: Yoshiaki Sonoda, Takafumi Kimura, Rumiko Asada, Takashi Kimura, Miho Morioka, Yutaka Sasaki, Susumu Ikehara
Journal: Blood (2006)
NIMG-20. IMAGING PATTERN ANALYSIS REVEALS THREE DISTINCT PHENOTYPIC SUBTYPES OF GBM WITH DIFFERENT SURVIVAL RATES
Authors: Saima Rathore, Hamed Akbari, Martin Rozycki, Spyridon Bakas, Christos Davatzikos
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM), the most aggressive primary malignant brain tumor, has heterogeneous subtypes exhibiting different morphologies and clinical characterizations. We aimed to undertake quantitative multi-parametric MRI analysis through advanced computational methods applied to 270 imaging and shape features to identify GBM phenotypic subtypes which might assist in defining more homogeneous patient sub-populations. Preoperative multi-parametric MRI data (i.e. T1, T1-Gad, T2, T2-FLAIR, DTI, and DSC) from 208 de novo GBM patients were retrospectively analyzed to extract imaging biomarkers. For each patient, we calculated volumetric, texture, shape, statistical, and histogram based features from all the modalities for enhancing tumor, non-enhancing tumor, and edema. The K-Means clustering algorithm was used on these features to identify different subtypes, which were validated on separate patient data through 10-fold cross-validation. The prominent phenotypic characteristics were determined and significance analysis was carried out using one-way ANOVA. We identified three distinct phenotypes. The first were rim-enhancing, primarily frontal lobe tumors, characterized by lower cell density, medium-sized edema, and average survival of 25 months. The second were irregularly-shaped, primarily occipital lobe tumors, with moderate cell density, large-sized edema, and average survival of 18 months. The third were solid, largely temporal lobe tumors, characterized by highest cell density, small-sized edema, and average survival of 9 months. Some of the discriminating features among these phenotypes were mean diffusivity (P=3.56x10-57), sphericity (P=6.92x10-19) and circularity (P=3.51x10-07) of non-enhancing tumor, and volume (P=1.53x10-15) and texture (P=8.60x10-15) of edema. Prediction of EGFRvIII mutation using these imaging features was more successful within each subtype (Avg. accuracy. 80.10%) compared to pooling all patients together (Accuracy. 72.97%). Machine learning methods noninvasively identified distinct subtypes of GBM by assessing quantitative imaging features. These phenotypes reveal more homogeneous characteristics, which can be helpful in personalized treatment of GBM and in patient selection in clinical trials.
NCOG-03. COGNITIVE FUNCTION AND QUALITY OF LIFE AMONG LONG TERM SURVIVORS OF BRAIN METASTASES
Authors: Michael Parsons, Jacob Miller, Rupesh Kotecha, Sally Vogel, Julia Biars, Manmeet Ahluwalia, Samuel Chao, Erin Murphy, John Suh, Gene Barnett
Journal: Neuro-Oncology (2016)

The development of brain metastasis (BM) from systemic cancer is associated with poor overall survival. However, a small subset of patients are able to overcome the likelihood of fatality in the first few years after central nervous system (CNS) involvement. Little is known about the quality of life and neurocognitive outcomes in these survivors. The records of 3643 patients who underwent treatment for BM with potential for ≥5 years of follow-up were reviewed from a single institution database. The median age at CNS involvement was 60 years and median OS was 7.6 months. The OS rate was 35 % at 1 year, 17% at 2 years, and 3.8% at 5 years. The 138 patients surviving ≥ 5 years had a median survival of 6.67 yrs. A small subset (17) of these survivors have completed neuropsychological evaluations during the survival period. Fourteen of these patients (82%) had initial treatment that included whole brain radiation therapy (WBRT). Fourteen (82%) had neurologic deficits (i.e., hemiparesis, visual field deficits, gait). KPS scores were ≥ 70 in seven of the patients (41%), whereas the remainder had scores of ≤60. On neuropsychological assessment, completed on average 6.8 years after neurologic involvement, 13 patients (76%) had cognitive impairment in at least one domain tested. Rates of impairment by domain were as follows: Memory 65%, Speed of processing 76%, Executive function 76%, Visuospatial processes 41%, and Language 31%. On mood related questionnaires, 30% endorsed at least a mild level of depression symptoms. Only 1 patient had neither neurologic sequelae nor cognitive impairment. A small percentage of BM patients have extended survival, but neurologic symptoms and neurocognitive deficits are common, which is often due to long term sequelae of the metastases themselves or treatment-related side effects. Factors that predict survival and favorable outcome are discussed.
INCB018424, an Oral, Selective JAK2 Inhibitor, Shows Significant Clinical Activity in a Phase I/II Study in Patients with Primary Myelofibrosis (PMF) and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF).
Authors: Srdan Verstovsek, Hagop Kantarjian, Animesh Pardanani, Deborah Thomas, Jorge Cortes, Ruben Mesa, John Redman, Carl-Michael Staschen, Jordan Fridman, Kris Vaddi, Ayalew Tefferi
Journal: Blood (2007)
Frozen in Time: The History of Proteins
Authors: Nicholas A. Kovacs, Anton S. Petrov, Kathryn A. Lanier, Loren Dean Williams
Journal: Molecular Biology and Evolution (2017)

The ribosome is imprinted with a detailed molecular chronology of the origins and early evolution of proteins. Here we show that when arranged by evolutionary phase of ribosomal evolution, ribosomal protein (rProtein) segments reveal an atomic level history of protein folding. The data support a model in which aboriginal oligomers evolved into globular proteins in a hierarchical step-wise process. Complexity of assembly and folding of polypeptide increased incrementally in concert with expansion of rRNA. (i) Short random coil proto-peptides bound to rRNA, and (ii) lengthened over time and coalesced into β-β secondary elements. These secondary elements (iii) accreted and collapsed, primarily into β-domains. Domains (iv) accumulated and gained complex super-secondary structures composed of mixtures of α-helices and β-strands. Early protein evolution was guided and accelerated by interactions with rRNA. rRNA and proto-peptide provided mutual protection from chemical degradation and disassembly. rRNA stabilized polypeptide assemblies, which evolved in a stepwise process into globular domains, bypassing the immense space of random unproductive sequences. Coded proteins originated as oligomers and polymers created by the ribosome, on the ribosome and for the ribosome. Synthesis of increasingly longer products was iteratively coupled with lengthening and maturation of the ribosomal exit tunnel. Protein catalysis appears to be a late byproduct of selection for sophisticated and finely controlled assembly.