tbuckley/cabot-search huggingface dataset:
S0204: Melphalan (MEL)-Based Tandem Autotransplants (TAT) for Multiple Myeloma (MM) with Thalidomide/Dexamethasone (TD) Induction and Thalidomide/Prednisone (TP) Maintenance: A Phase II Trial of the Southwest Oncology Group.
Authors: Mohamad A. Hussein, Andrzej J. Jakubowiak, Vanessa Bolejack, Jeff Zonder, John Crowley, Bart Barlogie
Journal: Blood (2006)
The Phenotype of Natural Killer (NK) Cells in Multiple Myeloma (MM) Patients: Impact on Ex Vivo Responsiveness to the Anti-SLAMF7 Antibody, Elotuzumab
Authors: Tatiana Pazina, Alexander MacFarlane, Ashley Mentik-James, Clinton Yam, Rebecca Kotcher, Kerry S. Campbell, Adam D. Cohen
Journal: Blood (2015)
Abstract 1137: Mitochondrial targeting of EGFR-VIII in temozolomide resistant glioblastoma models
Authors: Kiran Kumar Velpula, Swapna Asuthkar, Sarah E. Martin, Justin D. Lathia, Andrew J. Tsung
Journal: Cancer Research (2015)

Abstract Epidermal growth factor receptor (EGFR) over-expression is the most frequent genetic alteration associated with glioblastoma and has emerged as a highly attractive therapeutic target based on its high frequency of gene amplification and mutation as well as its deregulated cell signaling cascades that drive GBM pathophysiology. The genetic aberration of wtEGFR is often accompanied by the overexpression of a mutant EGFR known as EGFR variant III (EGFRvIII), which is expressed in 30% of GBM tumors. Despite recent innovations, may it be neurosurgical techniques, chemotherapeutics or molecular targeted therapies only few treatments showed promise. Temozolomide (TMZ) is one such and has shown improved survival in GBM when administered with concomitant radiotherapy. However, acquired TMZ chemoresistance occurs in more than 90% of recurrent GBMs. To delineate the mechanisms in the context of TMZ resistance, we generated an aggressive TMZ resistant model by continual exposure of U373 cells constitutively expressing EGFRvIII (U373vIII) to 150uM TMZ for 6 months (U373vIIIR). Our preliminary data showed that dichloroacetic acid (DCA) induced apoptosis and demonstrated reduced cell survival in the context of TMZ resistance. DCA treatment also demonstrated reduced EGFRvIII mitochondrial translocation in U373vIIIR cells. Micro array studies conducted on U373vIII or U373vIIR and their subsequent treatment with DCA revealed that PDK1 is the sole target in TMZ resistant tumors expressing EGFRvIII. Since EGFRvIII expression displays an aggressive phenotype yet remains tumor specific, we propose studying DCA alone or in combination with dasatinib, an inhibitor of EGFR subcellular translocation, in U373vIII and U373vIII-TMZ-R cell lines. By more accurately depicting the status of GBM at the time of recurrence after standard of care chemotherapy treatment, the investigation of DCA will augment and possibly redefine our current understanding of resistance mechanisms and establish novel methods of circumventing this pervasive phenomena. Note: This abstract was not presented at the meeting. Citation Format: Kiran Kumar Velpula, Swapna Asuthkar, Sarah E. Martin, Justin D. Lathia, Andrew J. Tsung. Mitochondrial targeting of EGFR-VIII in temozolomide resistant glioblastoma models. [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 1137. doi:10.1158/1538-7445.AM2015-1137
Abstract 2960: DNA promoter hypermethylation of genes as potential diagnostic and prognostic biomarkers for ovarian cancer
Authors: Blanca L. Valle, Elisabetta Kuhn, David Sidransky, Rafael Guerrero-Preston
Journal: Cancer Research (2015)

Abstract Till recently, epithelial ovarian cancers were thought to arise from the ovarian surface epithelial cells. However, recent studies suggest that the majority of high grade serous carcinomas (HGSCs) arise from lesions in the fallopian tubes. DNA promoter hypermethylation of certain genes is often an early event in tumorigenesis, and it can be detected in blood and other bodily fluids, making it a feasible biomarker strategy for early detection of tumors. Therefore, we sought to determine the methylation profile of HGSCs as compared to fallopian tube epithelium, using the Infinium HumanMethylation 450 Array. We compared the methylation in 12 HGSC tissue samples to 15 fallopian tube epithelium samples. In addition, we compared the methylation profile among long-term survivors (more than 5 years) and short-term survivors (2-3 years) of HGSCs. Our results identified the promoter regions of HIST1H2BB, MAGI2, and EPSTI1 to be differentially methylated when comparing HGSC with normal fallopian tube samples. Furthermore, these genes were differentially methylated in HGSC patients with long-term survival when compared to patients with short-term survival. Quantitative methylation specific PCR analysis confirmed our results of differential methylation among short-term and long-term survivors, and show that these genes are also methylated in ovarian cancer cell lines. Taken together, we have identified genes that could have potential as diagnostic and prognostic biomarkers. Our findings could lead to the development of a biomarker panel for the diagnosis and/or prognosis of ovarian cancer. Citation Format: Blanca L. Valle, Elisabetta Kuhn, David Sidransky, Rafael Guerrero-Preston. DNA promoter hypermethylation of genes as potential diagnostic and prognostic biomarkers for ovarian cancer. [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 2960. doi:10.1158/1538-7445.AM2015-2960
TRIM65-catalized ubiquitination is essential for MDA5-mediated antiviral innate immunity
Authors: Xueting Lang, Tiantian Tang, Tengchuan Jin, Chen Ding, Rongbin Zhou, Wei Jiang
Journal: The Journal of Experimental Medicine (2016)

MDA5 plays a critical role in antiviral innate immunity by functioning as a cytoplasmic double-stranded RNA sensor that can activate type I interferon signaling pathways, but the mechanism for the activation of MDA5 is poorly understood. Here, we show that TRIM65 specifically interacts with MDA5 and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. Trim65 deficiency abolishes MDA5 agonist or encephalomyocarditis virus (EMCV)–induced interferon regulatory factor 3 (IRF3) activation and type I interferon production but has no effect on retinoic acid–inducible I (RIG-I), Toll-like receptor 3 (TLR3), or cyclic GMP-AMP synthase signaling pathways. Importantly, Trim65−/− mice are more susceptible to EMCV infection than controls and cannot produce type I interferon in vivo. Collectively, our results identify TRIM65 as an essential component for the MDA5 signaling pathway and provide physiological evidence showing that ubiquitination is important for MDA5 oligomerization and activation.
Abstract 1908: Evaulate biomarkers in NSCLC tumors receiving neoadjuvant chemotherapy
Authors: Apar Pataer, Ruping Shao, Arlene M. Correa, Carmen Behrens, Jack A. Roth, Ignacio I. Wistuba, Stephen G. Swisher
Journal: Cancer Research (2015)

Abstract In previous study, we have evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease free survival (DFS) and observed that the percentage of residual viable tumor cells were associated with OS and DFS in 192 NSCLC patients receiving neoadjuvant chemotherapy. In current study, we examined the selected protein biomarkers by IHC in surgical specimens of 98 NSCLC patients receiving neoadjuvant chemotherapy. All NSCLC patients treated with neoadjuvant chemotherapy received a platinum and taxane-based. For IHC analysis of protein markers, we selected candidate biomarkers (VEGFR2, EZH2, ERCC1 and Rad51) on the basis of the literature. Next, the results of VEGFR2, EZH2, ERCC1 and Rad51 expression were analyzed with regard to pathologic response and overall survival time of the patients. The surgical pathologic stage, percentage of viable tumor cells and Rad51 were associated with OS in 98 NSCLC patients receiving neoadjuvant chemotherapy in univariate and multivariate analysis. We found that patients with high-level expression of Rad51 had a poorer prognosis than did those with low-level expression. We observed that Rad51 expression was associated with pathologic response (viable tumor cells). However, there is no association between VEGFR2, EZH2, or ERCC1 expression and pathologic response (viable tumor cells). We further examined K-Ras and EGFR Mutation in these NSCLC tumors receiving neoadjuvant chemotherapy. We analyzed the hotsport mutations in K-Ras gene (Codon 12 and 13) and EGFR gene (Exon 19 and 21) by pyrosequencing and confirmed by direct sequencing method in 98 NSCLC tumors receiving neoadjuvant chemotherapy. We observed both methods had similar results on these patients’ samples. The L858R mutation results in an amino acid substitution at position 858 in EGFR, from a leucine (L) to an arginine (R). This mutation occurs within exon 21, which encodes part of the kinase domain,We found K-Ras mutation tended to be associated with OS, but not EGFR mutation. There is no association between percentage of viable tumor cells, VEGFR2, EZH2, ERCC1, Rad51 expression and K-Ras or EGFR mutation. Citation Format: Apar Pataer, Ruping Shao, Arlene M. Correa, Carmen Behrens, Jack A. Roth, Ignacio I. Wistuba, Stephen G. Swisher. Evaulate biomarkers in NSCLC tumors receiving neoadjuvant chemotherapy. [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 1908. doi:10.1158/1538-7445.AM2015-1908
Improved Engraftment without Graft-Versus-Host Disease After MHC-Mismatched Cord Blood Transplantation with Photochemically Treated Donor Lymphocytes.
Authors: Bindu Kanathezhath, Myra Mizokami, Lynne Neumayr, Hua Guo, Mark C. Walters, Frans A. Kuypers
Journal: Blood (2009)
693. Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations
Authors: Alice Moussy, Jérémie Cosette, Fanny Onodi, Adrien Auffret-Cariou, Thi My Anh Neildez-Nguyen, Andras Paldi, Daniel Stockholm
Journal: Molecular Therapy (2016)

The host's immune response is a frequent obstacle to successful gene therapy. The suppressive activity of regulatory T cells can be used to get round the problem. To do this, understanding the mechanism of proliferation and differentiation of CD4 + T cells is necessary. Here, we used time-lapse microscopy of individual murine CD4 + T cells to investigate the dynamics of proliferation and fate commitment. We observed highly heterogeneous division and death rates between individual clones resulting in a Pareto-like dominance of a few clones at the end of the experiment. Commitment to the regulatory T (Treg) fate was monitored using the expression of a GFP reporter gene under the control of the endogenous Foxp3 promoter. All possible combinations of proliferation and differentiation were observed and resulted in exclusively GFP-, GFP+ or mixed phenotype clones of very different population sizes. We simulated the process of proliferation and differentiation using a simple mathematical model of stochastic decision-making based on the experimentally observed parameters. The simulations show that a stochastic scenario is fully compatible with the observed Pareto-like imbalance in the final population. These observations may help to develop new strategies for the amplification of Treg cells for therapeutic use.
Abstract LB-036: Neuronal activity-regulated secretion of neuroligin-3 promotes glioma growth
Authors: Humsa Venkatesh, Tessa Johung, Viola Caretti, Parag Mallick, Michelle Monje
Journal: Cancer Research (2015)

Abstract Active neurons exert a mitogenic effect on normal neural precursor and oligodendroglial precursor cells, the putative cellular origins of high-grade glioma (HGG). We demonstrate that active neurons similarly promote HGG proliferation and growth in vivo using optogenetic control of cortical neuronal activity in a patient-derived pediatric glioblastoma orthotopic xenograft model. Activity-regulated mitogen(s) are secreted, as the conditioned medium from optogenetically stimulated cortical slices promoted proliferation of pediatric and adult patient-derived HGG cultures. The synaptic protein neuroligin-3 (NLGN3) was identified as the leading candidate mitogen; soluble NLGN3 was sufficient and necessary to promote robust HGG cell proliferation. NLGN3 induced PI3K-mTOR pathway activity and feed-forward expression of NLGN3 in glioma cells, providing mechanistic insight into its surprising role as a mitogen. NLGN3 expression levels in human HGG negatively correlated with patient overall survival. These findings indicate the important role of active neurons in the brain tumor microenvironment and identify secreted NLGN3 as an unexpected mechanism promoting neuronal activity-regulated cancer growth. Citation Format: Humsa Venkatesh, Tessa Johung, Viola Caretti, Parag Mallick, Michelle Monje. Neuronal activity-regulated secretion of neuroligin-3 promotes glioma growth. [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 LB-036. doi:10.1158/1538-7445.AM2015-LB-036
Systems Understanding of Synergism Between As4S4 and Imatinib in Treating BCR/ABL Leukemia Model and in Attenuating BCR/ABL Oncoprotein as Well as Related Regulatory Networks
Authors: Qun-Ye Zhang, Jian-Hua Mao, Ping Liu, Qiu-Hua Huang, Jing Lu, Yan Zhang, Lin Weng, Quan Chen, Sai-Juan Chen, Zhu Chen
Journal: Blood (2008)
Chronic Lymphocytic Leukemia (CLL) with Discordance in ZAP-70 Expression and IgVH Mutation Status.
Authors: Ilaria Del Giudice, Emanuela M. Ghia, Stefania M. De Propris, Marilisa Marinelli, Mauro Nanni, Francesca Mancini, Massimo Gentile, Elena Giammartini, Elisabetta Calabrese, Francesca R. Mauro, Anna Guarini, Robert Foa
Journal: Blood (2006)
642. NDRG4 Is a Novel Therapeutic Target in Malignant Meningioma and Its Loss Induces Apoptosis
Authors: Rama P. Kotipatruni, Xuan Ren, Dinesh Thotala, Jerry J. Jaboin
Journal: Molecular Therapy (2015)

NDRG4 is a member of the N-Myc downstream regulated gene family belonging to the alpha/beta hydrolase super family. The roles of NDRG4 in meningioma tumor development have not previously been evaluated. Effective local therapies include surgery and radiation, but there is a need for novel molecular targets to improve survival and reduce morbidity for meningioma patients. We have recently identified the NDRG4 protein as being overexpressed in aggressive meningiomas. We have demonstrated that NDRG4 downregulation results in decreased cell proliferation, migration and invasive properties. In follow up to our prior studies on the effects of NDRG4 gene silencing in IOMM-Lee and CH-157 MN meningioma cell lines; here we demonstrate that the predominant form of cell death is apoptosis, utilizing Annexin-V flow cytometry assay. We show that apoptosis caused by upregulation of p53, phosphorylation of p53 at ser 15, Bax activation and downregulation of Bcl-2 and BcL-xL along with cytochrome c release from mitochondria and execution of caspases after depletion of NDRG4. The proapoptotic effect of p53 was verified by the results in which a small molecule compound PFT-α, an inhibitor of p53 phosphorylation, is greatly protected against targeting NDRG4 induced apoptosis. Sub-cellular distribution of Bax and cytochrome c indicated mitochondrial-mediated apoptosis. In addition, we carried out the fluorescence cytohemcial analysis to confirm the mitochondrial-mediated apoptosis by changes in mitochondrial membrane potential (Ym), using JC-1 dye. These findings bring novel insight to the roles of NDRG4 in meningioma tumor cell progression. We hypothesized that NDRG4 has played crucial role in regulating the p53 by its molecular interactions. Binding of NDRG4 with p53 was confirmed by Immunoprecipitation and double Immunocolocalization was verified by confocal microscopy. In conclusion, we show that NDRG4 is predominantly a cytosolic protein expressed in response to cell proliferation and demonstrated the suppression of NDRG4 induces the apoptosis through p53 activated and mitochondrial mediated apoptotic pathway. This therapeutic strategy may have promise in the management of meningiomas.
Characterisation of Novel Hypomorphic and Null Mutations in Klf1 Derived from a Genetic Screen for Modifiers of a-Globin Transgene Variegation
Authors: Stephen Huang, Kevin R. Gillinder, Melissa Ilsley, Graham Magor, Michael Tallack, Anabel Sorolla, Harald Oey, Sarah Harten, Lucia Clemens-Daxinger, Emma Whitelaw, Andrew C Perkins
Journal: Blood (2015)
Onset to Door Time Attenuates the Impact of Door to Balloon Time on In-hospital Mortality :AMI-Kyoto Multi-Center Risk Study Group
Authors: Nakamura Takeshi, Sawada Takahisa, Yamano Tetsuhiro, Shiraishi Jun, Matsumuro Akiyoshi, Matsubara Hiroaki, Kohno Yoshio, Kitamura Makoto, Furukawa Keizo
Journal: Circulation (2011)
Abstract 642: Effect of Acute and Chronic Stretch on the Pulmonary Veins in Humans: Implications for Arrhythmogenic Triggers
Authors: Bobby John, Anthony G Brooks, Pawel Kuklik, Sunil T Chandy, Prashanthan Sanders
Journal: Circulation (2008)

Introduction Stretch is characteristic of most conditions predisposed to atrial fibrillation (AF). However, there is no human data on effect of atrial stretch on pulmonary veins (PV), the dominant trigger of AF Method Two groups were studied; Group A (n=12; 31±7 yrs) undergoing left sided accessory pathway ablation and Group B (n=12; 29±7 yrs) undergoing percutaneous valvuloplasty for mitral stenosis (MVA 0.9±0.3 cm 2 ). Multi-electrode basket catheter was positioned in the PVs to perform high-density mapping using NavX system to determine: proximal/ distal effective refractory period (ERP); conduction time (CT); intra-PV conduction block (CB; ≥30ms between adjacent poles) resulting in circuitous conduction during the drive (S 1 ) and pre-excited stimulus (S 2 ); and intra-PV voltage. Effect of acute stretch was determined in Group A by simultaneous RV and PV pacing and chronic stretch in Group B Results Twenty-four PVs were studied in each group. Acute stretch (Group A) resulted in ERP shortening (240±33 to 225±39 ms; p=0.03), prolonged CT with S 2 , which increased further with stretch (77±30 to 88±37ms; p=0.02). Intra-PV CB became prominent with S 2 and accentuated with stretch (40±23 to 59±32ms; p&lt;0.0001). The changes were not site specific. Left atrial volume (p=0.001) and pressure (p=0.04) were elevated in Group B. Unlike acute stretch, ERP was prolonged, conduction delayed in sinus rhythm (p=0.005) and S 1 which further accentuated with S 2 (refer Table ). Intra-PV CB was seen at S 2 . Additionally, mean bipolar voltage was reduced (0.8[0.3–3.5] mV vs 1.4[0.8–3.7] mV; p=0.005) Conclusion Acute stretch results in abbreviation of PV ERP while chronic prolongs it. Nevertheless, both cause marked PV conduction abnormalities that are pronounced with chronic stretch and extra-stimuli. Additionally, structural remodeling was seen with chronic stretch. These abnormalities implicate stretch in the milieu for re-entry and PV arrhythmogenesis in conditions predisposed to AF Electrophysiological characteristics
Next-Generation Sequencing of the BCR-ABL1 Kinase Domain and Neighboring Domains Associated with Therapy Resistance.
Authors: Jin Li, Weihua Liu, Zhenyu Yan, Peng Fang, Agus Darwanto, Kim Pelak, Julie Toplin, Kim Anoe, Cindy Spittle, Chad Galderisi, Stephane Wong
Journal: Blood (2012)
Treatment Outcomes in Multiple Sclerosis (MS) Patients after Early, Conventional and Salvage High Dose Chemotherapy (HDCT)+Autologous Stem Cell Transplantation (ASCT).
Authors: Yury L. Shevchenko, Andrei A. Novik, Boris V. Afanasiev, Igor A. Lisukov, Tatiana I. Ionova, Andrei D. Kulagin, Olga A. Malysheva, Gennady N. Bisaga, Vladimir J. Melnichenko, Sergei V. Voloshin, Denis A. Fedorenko, Inna V. Vereschagina, Anton V. Kishtovich, Yury N. Fedotov, Gary I. Gorodokin
Journal: Blood (2005)
Silencing of Genes Required for Glycosylphosphatidylinositol Biosynthesis in a Burkitts’ Lymphoma Cell Line (Ramos) and Hematopoietic Stem Cells (HSC).
Authors: Rong Hu, Galina L. Mukhina, Michael I. Collector, Soo Hee Lee, Richard J. Jones, Xuan Yuan, Paul T. Englund, Thomas Buckley, Saul J. Sharkis, Robert A. Brodsky
Journal: Blood (2006)
Translocation renal cell carcinomas: An evolving entity.
Authors: Derek Gerard Power, Jodie E Battley, Aoife McCarthy, Claire Brady, John P. Sweeney, Stewart Fleming, Nicholas J. Mayer, Richard Martin Bambury
Journal: Journal of Clinical Oncology (2012)

e15078 Background: Translocation renal cell carcinomas (tRCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. These neoplasms are only recently recognised and outcome data are premature. We report 2 cases of tRCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: : Approximately 70 new cases of RCC are referred to our centre annually. Recently, 2 renal cell carcinomas were suspected to be tRCCs on morphology and immunohistochemical(IHC) features (RCC+/CK7-/EMA-). Using IHC we tested for expression of TFE3 and TFEB. Results: : Both tumours were tRCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 RCC with mixed clear cell and papillary architecture. IHC for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She relapsed 9 months later with local recurrence, retroperitoneal adenopathy and lung metastases. She commenced sunitinib and response assessment is pending. The 2nd case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen. Staging CT revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. IHC for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 9 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and will also report 3 further cases suspected to be tRCCs based on morphology and IHC. Confirmatory TFE3/TFEB IHC is awaited.