tbuckley/cabot-search huggingface dataset:
Abstract 283: Smac mimetic and radiotherapy synergize to enhance antitumor immunity in lung cancer by targeting immunosuppressive cells
Authors: Zhen Tao, Carey Myers, Norbert Wiedemann, Gregoire Vuagniaux, Larry Harshyne, Adam Dicker, D. Craig Hooper, Bo Lu
Journal: Cancer Research (2015)

Abstract Purpose Hypofractionated radiotherapy (RT) directly kills lung cancer cells and stimulates tumor antigen release, the immune response to which can be augmented further by systemic immune-modulating agents. However, local relapses often occur after RT alone, indicating that inhibitory mechanisms may limit the anti-tumor immune responses elicited by apopotic tumor cells. We hypothesized that delivery of Smac mimetic, which sensitizes cells to apoptosis by counteracting the activity of inhibitor of apoptosis (IAP) proteins, following RT might lead to prolonged antitumor immunity by promoting the destruction of immunosuppressive myeloid cells. Experimental Design Using a murine model of lung cancer, we tested whether combination treatment with radiotherapy and the Smac mimetic Debio1143 would target immunosuppresive myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and enhance the efficacy of cytotoxic T cells. Results We demonstrate that administration of Debio1143 enhances the efficacy of RT by inducing LLC and LLC-OVA cells apoptosis in vitro. In addition, we show that combining radiotherapy and Debio1143 in vivo synergistically reduces the local accumulation of tumor-infiltrating MDSCs through a cytotoxic T cell-dependent mechanism. Activation of cytotoxic T cells by combination therapy proved to be mediated through the enhanced release of tumor necrosis factor alpha (TNF-α) in the tumor microenvironment. Conclusions These data offer a new paradigm to limit immunosuppresion by targeting MDSC and serve as the foundation for future clinical translation of combination therapy with Smac mimetics and radiotherapy. Citation Format: Zhen Tao, Carey Myers, Norbert Wiedemann, Gregoire Vuagniaux, Larry Harshyne, Adam Dicker, D. Craig Hooper, Bo Lu. Smac mimetic and radiotherapy synergize to enhance antitumor immunity in lung cancer by targeting immunosuppressive cells. [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 283. doi:10.1158/1538-7445.AM2015-283
Immunochromatography Method Was Useful in Prompt Diagnosis of Potentially Fatal Norovirus Gastroenteritis After Hematopoietic Stem Cell Transplantation
Authors: Ryosuke Ueda, Nobuhiro Hiramoto, Shin-Ichiro Mori, Saiko Kurosawa, Takashi Tanaka, Kohei Tada, Yujin Kobayashi, Noriyuki Morikawa, Akihito Shinohara, Keiji Okinaka, Takuya Yamashita, Yuji Heike, Takahiro Fukuda
Journal: Blood (2011)
OP9-DL1 Cell Line Supports the Development of Phenotypically and Functionally Mature Tcrαβ And Tcrγδ T Cells, through Both Conventional and Aberrant Developmental Pathways
Authors: Tessa C. C. Kerre, Greet Verstichel, Stefanie Van Coppernolle, Imke Velghe, Frank Timmermans, Jean Plum, Bart Vandekerckhove
Journal: Blood (2008)
Impact of White Blood Cell Count Recovery On Clinical Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Haesook T Kim, David G Frederick, Emily Andler, Philippe Armand, Grace Kao, Corey Cutler, John Koreth, Edwin Alyea, Joseph H Antin, Robert J Soiffer, Jerome Ritz, Vincent T. Ho
Journal: Blood (2012)
Deletion of Sbds from Hematopoietic Progenitors Causes Neutropenia in a Mouse Model of Shwachman-Diamond Syndrome By Specifically Blocking Myeloid Lineage Progression at Late Differentiation Stages
Authors: Noemi A. Zambetti, Paulina M.H. Van Strien, Marijke G. Valkhof, Maria N. Adisty, Eric M. J. Bindels, Remco M. Hoogenboezem, Mathijs A. Sanders, Johanna M. Rommens, Ivo P. Touw, Marc H.G.P. Raaijmakers
Journal: Blood (2014)
Phase II Trial of Lenalidomide (Revlimid™) with Cyclophosphamide and Dexamethasone (RCd) for Newly Diagnosed Myeloma
Authors: Shaji Kumar, Suzanne Hayman, Francis Buadi, Martha Lacy, Keith Stewart, Jacob Allred, Kristina Lauman, Tammy McCarty, Leif Bergsagel, David Dingli, Rafael Fonseca, Morie Gertz, Philip Greipp, John Lust, Stephen Russell, Craig Reeder, Thomas Witzig, Steven Zeldenrust, Robert Kyle, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2008)
Delta T1 (dT1) method as a tool to evaluate tumor progression in patients with brain cancer.
Authors: D. Bedekar, K. M. Schmainda, S. Rand, J. M. Connelly, M. G. Malkin, E. Paulson, W. Mueller
Journal: Journal of Clinical Oncology (2011)

e21056 Background: Evaluation of pre- and post-contrast T1-weighted images is the primary approach to monitoring patients with brain tumors. The pre-contrast images are used to distinguish enhancing lesions on the post-contrast images from other sources of bright signal such as subacute hemorrhage or protein-containing fluid, which appear bright on the T1-weighted pre-contrast image. However, in some cases additional enhancement observed on the post-contrast images, above and beyond the brightness observed on the pre-contrast images, can be quite subtle and thus difficult to detect by direct inspection. Methods: As a solution we have developed an automatic method, the delta T1 (dT1) method, for selection of regions of interest by creating difference maps between standardized pre- and post-contrast T1-weighted images. The dT1 method is a fast, reliable and objective method to detect even subtly enhancing tumors free of blood products. Results: In this study we report the use of technique, dT1 method, for two main applications: a) Detection of tumor residual upon surgery: The dT1 method can aid in distinguishing blood products from residual tumor. b) Early detection of tumor recurrence: The dT1 is highly sensitive to even subtle changes in post-contrast images that can be missed by direct inspection. This condition occurs more frequently with the increasing use of anti-angiogenic agents which make it increasingly difficult to monitor patients with brain tumors simply by visually comparing differences in enhancement. Conclusions: We calculated dT1 maps for patients and correlated dT1 results with time to progression as seen on clinical scans. For all cases for which the dT1 maps were suggestive of the presence of tumor the time to progression was much shorter (3-7 months) compared to dT1 maps with a negative (-) ROI status. We therefore conclude that dT1 method has the potential to serve valuable tool for monitoring patients over time. Patient No. Gender Age Diagnosis dT1 map (ROI status) Time to progression 1 M 50 Glioblastoma + 5 months 2 F 65 Glioblastoma + 3 months 3 F 67 Anaplastic oligodendroglioma + 7 months 4 M 45 Astrocytoma + 4 months 5 M 60 Anaplastic oligoastrocytoma + 3 months 6 F 53 Glioblastoma - 18 months 7 F 41 Oligodendroglioma - 13 months
Results of a randomized phase IIb study estimating overall survival of pralatrexate versus erlotinib in platinum-pretreated NSCLC.
Authors: J. D. Patel, C. G. Azzoli, G. A. Weems, A. Koutsoukos, P. Zatloukal, K. Kelly
Journal: Journal of Clinical Oncology (2011)

7554 Background: Pralatrexate (PDX) is a folate analog targeting dihydrofolate reductase. A previous phase I trial in heavily pretreated patients (pts) with advanced NSCLC reported a 10% overall response rate, including 2 pts with durable complete response (26+ and 21+ months; Azzoli, ESMO 2009). Erlotinib (ERL), an EGFR tyrosine kinase inhibitor, is approved for use in NSCLC. The objectives of this study were to compare PDX with ERL in current and former smokers with advanced NSCLC after failure of platinum-based therapy. Methods: Pts were randomized 1:1 to PDX 190 mg/m² (230 mg/m² initially) IV on days 1 and 15 of a 28-day cycle or ERL 150 mg/d PO. The primary objective was to estimate overall survival (OS) of PDX vs ERL, including prespecified subgroups. Results: Baseline characteristics for the 201 enrolled pts were balanced except for histology; 29% vs 47% had squamous carcinoma and 61% vs 46% had nonsquamous carcinoma in the PDX and ERL arms, respectively. Efficacy: The hazard ratio (HR; 95% CI) for OS was 0.84 (0.61, 1.14). PDX OS benefit trend was greatest in pts with nonsquamous histology (n=107; HR=0.65). The activity of PDX was comparable to ERL in pts with squamous cell carcinoma (HR=1.06). An analysis adjusting for histology showed consistency with the overall results (HR=0.82). The median progression-free survival was 3.4 vs 2.8 months in the PDX and ERL arms (HR = 0.91). Safety: Safety profiles of both agents were consistent with those previously identified. The most common adverse event (AE) was mucositis with PDX (Grade 1, 2, 3, 4 = 11%, 34%, 20%, 3%) and rash with ERL (Grade 1, 2, 3, 4 = 28%, 28%, 8%, 0%). Grade 0 mucositis was required for retreatment. Only 1 dose reduction was allowed for AEs. In the PDX arm, 21% of pts discontinued due to mucositis; most discontinuations occurred in cycle 1. A landmark analysis of pts who remained on treatment at 30 days showed an OS benefit trend favoring PDX (HR= 0.61). Conclusions: Most pt groups with advanced NSCLC showed trends for greater OS benefit from PDX compared to ERL. Individualized dose-modification strategies and prospective mucositis management to maximize benefit and tolerability of pralatrexate will be key success factors in future trials.
Place de la radiofréquence dans la prise en charge des occlusions de prothèses biliaires métalliques
Journal: Endoscopy (2016)

Le drainage biliaire par prothèse métallique auto-expansible (SEMS) est un standard dans la prise en charge des sténoses malignes chez le patient avec une espérance de plus de 4 mois selon les recommandations européennes. Cependant, la durée de perméabilité médiane des SEMS est limitée à 6 – 8 mois en raison d’occlusions par phénomènes de ré-épithélialisation ou de progression tumorale locale. L’ablation des tissus par radiofréquence (RFA), technique induisant une nécrose tissulaire, a montré sa faisabilité et son efficacité dans quelques études préliminaires. Ce travail avait donc pour but d’évaluer l’efficacité de la RFA dans les cas d’occlusion prothétique.
Abstract 5432: Discovery and characterization of USP22 inhibitors as novel anti-cancer agents
Authors: Feng Wang, Timothy R. Stanek, Leelabati Biswas, Matthew Kodrasov, James LaRocque, Jian Wu, David Sterner, Joseph Weinstock, Michael Mattern, Steven B. McMahon, Suresh Kumar
Journal: Cancer Research (2015)

Abstract The degradation of most cellular proteins is regulated by coordinated addition and removal of ubiquitin by families of ubiquitin E3 ligases and deubiquitylating enzymes (DUBs) respectively. DUBs proteolytically cleave ubiquitin molecules from proteins resulting in modifications of protein activity, localization and function. Several DUBs are aberrantly regulated in cancer, including the best studied, USP7, selective inhibitors of which are active in cancer models. USP22, is another validated anticancer target, being one of 11 genes in the death-from-cancer gene signature, a component of the human SAGA transcriptional cofactor complex regulating myc transcription, and a regulator of the expression of p21, the histone deacetylase Sirt 1, and p53 activity. USP22 is overexpressed in oral squamous cell carcinoma, breast, non-small cell lung, colorectal, and other cancers and its expression is inversely correlated with survival. Unlike most other DUBs, USP22 exhibits robust activity only as a component of a multi-subunit complex. Initial studies reported activity solely as a member of the 2MDa SAGA complex, but more recently it has been demonstrated that USP22 exhibits similar activity in a four-protein DUB module derived from the SAGA complex. USP22 inhibitors are expected to have broad anti-cancer activities. Progenra's UbiProTM discovery platform was utilized to screen ∼200K member diversity based library of small molecules for identifying novel USP22 inhibitors. Data will be presented describing these results. Citation Format: Feng Wang, Timothy R. Stanek, Leelabati Biswas, Matthew Kodrasov, James LaRocque, Jian Wu, David Sterner, Joseph Weinstock, Michael Mattern, Steven B. McMahon, Suresh Kumar. Discovery and characterization of USP22 inhibitors as novel anti-cancer agents. [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 5432. doi:10.1158/1538-7445.AM2015-5432
642. Oncolytic Vaccines with Modified Tumor Epitopes for Cancer Immunotherapy
Authors: Cristian Capasso, Aniket Magarkar, Victor Cerveca Carrascon, Martin Muller, Mariangela Garofalo, Lukasz Kuryk, Davide Cardella, Karita Peltonen, Alex Bunker, Vincenzo Cerullo
Journal: Molecular Therapy (2016)

Oncolytic adenoviruses (OAds) are capable of killing tumor cells while activating the immune system due to their immunogenicity. Hance, they are an excellent platform for oncolytic vaccine. We previously demonstrated that the injection of peptide-coated conditionally replicating adenoviruses (PeptiCRAd) is capable of reducing the growth of established aggressive melanomas (murine B16). Oncolytic vaccines, like PeptiCRAds, often rely on inducing an immune response against specific tumor antigens. However, many tumor antigens are also self-antigens, hence the peripheral tolerance might impair the activity of tumor-reactive T-cells. Therefore, mutated epitopes represent an optimal tool to break the tolerance, exploiting the cross-reactivity of T-cells. To this end we developed an Epitope Discovery and Improvement System (EDIS) framework to study native epitopes and predict, in silico, mutated forms suitable for cancer therapy. The novel aspect of EDIS is the ability to interrogate different prediction servers, integrate the different results and validate these by molecular dynamics simulations. We started by studying the model epitope SIINFEKL. According to our in silico predictions, two mutated variants were suggested to be more immunogenic than the native SIINFEKL peptide. To test whether this prediction would reflect in enhanced vaccine effect we studied the immune response against these peptides in B16-OVA bearing mice. Mice were challenged with B16-OVA and treated with three different PeptiCRAds coated with SIINFEKL and the two predicted derivates. By ELISPOT assay we assessed the anti-peptide response and demonstrated that the two mutated forms were in fact more effective in reducing the growth of established B16OVA tumors. Finally, we studied the native epitope SVYDFFVWL from the tyrosinase-related protein 2 (TRP2), a melanoma antigen in clinical evaluation. By using the EDIS framework we selected two mutated variants that show increased MHC-I binding affinity and we tested them by treating aggressive B16F10 tumors. As expected, treatment with the native TRP2 reduced the growth of the tumors compared to the controls. Suprisingly, one of the two analogues improved significantly the survival of mice and reduced the growth of their tumors compared to the group treated with the native TRP2 epitope. In conclusion, we demonstrated that the integration of different in silico methods increases the accuracy when predicting mutated epitopes for cancer immunotherapy.
Having Cancer and Seeking the Point
Authors: Meredith L. Clements
Journal: Annals of Internal Medicine (2016)

Ad Libitum20 December 2016Having Cancer and Seeking the PointMeredith L. Clements, MAMeredith L. Clements, MAFrom University of South Florida, Tampa, Florida.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-2480 Audio Reading - “Having Cancer and Seeking the Point” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Having Cancer and Seeking the Point," by M.L. Clements. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Each morning, I sip coffee on the porchWatching the backyard come aliveDeer walk their usual path through my gardenOne locks my gaze, andI remember to breatheShe recognizes meI sit straight, trying to present my best SelfYet she remains underwhelmed by my presenceIn this moment I become more mindfulThere is humor in thinking nature might stop for mePerhaps the point of cancerIs to recognize the uncomplicated nature of dying?Like the deer, I am not intimidatedI have locked death's gazeRefusing to blink firstCancer brings me ... Author, Article, and Disclosure InformationAffiliations: From University of South Florida, Tampa, Florida.Current Author Address: Meredith L. Clements, MA, University of South Florida, 4202 East Fowler Avenue, Tampa, FL 33620; e-mail, [email protected]usf.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Having Cancer and Seeking the Point” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Having Cancer and Seeking the Point," by M.L. Clements. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 20 December 2016Volume 165, Issue 12Page: 883KeywordsCoffee ePublished: 20 December 2016 Issue Published: 20 December 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Mutations Innate Immune System NOD/CARD15 Gene and Toll-Like-Receptor-4 Gene Are Associated with Increased Risk for Severe Acute Gvhd in Patients Who Underwent Allogeneic Transplantation.
Authors: Ahmet H. Elmaagacli, Michael Koldehoff, Nina K. Steckel, Heidrun Hindahl, Rudolf Trenschel, Hellmut Ottinger, Dietrich W. Beelen
Journal: Blood (2004)
Abstract 214: Characterization of the near-infrared fluorescent protein iRFP for plate-based assays and animal imaging
Authors: Haibiao Gong, Joy L. Kovar, Teresa Urlacher
Journal: Cancer Research (2015)

Abstract Fluorescence imaging has been extensively used in biological research because of its high sensitivity, signal stability, and simplicity of multiplexing. Compared to fluorophores in the visible spectral region, fluorophores with excitation (Ex) and emission (Em) maxima in the near-infrared (NIR) region (700-900 nm) are desirable in many applications. Cells, buffers and plastic materials generate less background fluorescence in the NIR region. As a result, NIR fluorescence imaging offers higher sensitivity and better signal-to-background ratio (SBR) compared to visible fluorescence. In addition, due to the reduced light absorption and scattering in animal tissues, NIR fluorescence is particularly suitable for in vivo imaging studies. In this study, we characterized the NIR fluorescent protein iRFP for plate-based assays and animal imaging. HEK293 cells stably expressing iRFP were established and designated as HEK293-iRFP. Serial dilutions of HEK293-iRFP cells were seeded in 96-well plate and scanned on the Odyssey CLx Imaging System. A good linear relationship between fluorescence signal intensity and cell number was obtained. The lower limit-of-detection was determined as 763 cells. To evaluate the performance of iRFP for animal imaging, the iRFP-expressing plasmid was delivered into mouse liver cells using a hydrodynamic injection method. A dose- and time-dependent pattern of fluorescence signal was observed after plasmid injection. At 8 h post-injection of 10 μg of iRFP plasmid, a SBR of 41 was observed by live animal imaging. Analysis of liver tissue lysates revealed a SBR of 148. Other tissues, including kidney, spleen, heart and lung, showed very little fluorescence signal. Our results demonstrate that iRFP is a good reporter for both plate-based assays and animal imaging studies. Citation Format: Haibiao Gong, Joy L. Kovar, Teresa Urlacher. Characterization of the near-infrared fluorescent protein iRFP for plate-based assays and animal imaging. [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 214. doi:10.1158/1538-7445.AM2015-214
PRELIMINARY COMMUNICATION ON THE DISCREPANCY BETWEEN RENIN ACTIVITY AND HYPERTENSION-INDUCING POTENCY IN RAT KIDNEY EXTRACT DUAL RENAL PRESSOR SUBSTANCE HYPOTHESIS
Authors: Jun Kira, Katsuya Ohnishi, Jin Yamamoto, Nobuya Konishi, Kaname Yamatori, Takashi Kamiguchi
Journal: Circulation (1971)
Bendamustine As Salvage Therapy in Multiple Myeloma: A Retrospective, Multicenter Study From the Italian Compassionate Use Program in 78 Heavily Pre-Treated Patients.
Authors: Pellegrino Musto, Vincenzo Ludovico Fraticelli, Giovanna Mansueto, Giovanni D'Arena, Maria Pia Petrilli, Cristiana Gasbarrino, Giuliana Farina, Roberto Guariglia, Maria Carmen Martorelli, Oreste Villani, Giuseppe Pietrantuono, Lucio Catalano, Emanuela Madonna, Andrea Nozza, Alessandro Andriani, Vittorio Montefusco, Alberto Mussetti, Maria Grazia Lipari, Stelvio Ballanti, Velia Bongarzoni, Stefania Tamiazzo, Francesca Patriarca, Donatella Vincelli, Antonietta Falcone, Daniele Derudas, Catello Califano, Renato Zambello, Giuseppe Mele, Alberto Fragasso, Luca Baldini, Antonio Palumbo, Sergio Storti
Journal: Blood (2012)
Abstract 2644: Inhibition of PAK4 attenuates renal cell carcinoma (RCC) growth
Authors: Omran Abu Aboud, William Senapedis, Yosef Landesman, Erkan Baloglu, Robert H. Weiss
Journal: Cancer Research (2015)

Abstract Renal cell carcinoma (RCC) is an increasingly prevalent cancer type that is frequently asymptomatic on presentation and is associated with poor responses and resistance even to the current targeted therapies. Thus, novel therapeutic approaches to treat this disease are urgently needed. P21-activated kinase 4 (PAK4) is a mediator of filopodia formation and stabilizes β-catenin transcriptional activity. PAK4 lies in a pathway integral to both nephrogenesis and cancer. We hypothesized that inhibitors of the PAK4 signaling pathway would result in salutary effects on RCC. To test this, we evaluated the in vitro response of RCC cells to the specific PAK4 Allosteric Modulators (PAMs; KPT-8752 and KPT-9274). Similar to cells of other cancer types, 786-O (VHL-mutant RCC) showed decreases of both Phospho-PAK4 and Phospho-β-catenin after 24 h of incubation with 10 μM KPT-8752. In addition, both 786-O and ACHN (VHL-wildtype RCC cells) showed a marked time-dependent decrease in cell viability from 24 to 72 h of incubation from 2 to 10 μM of KPT-8752. KPT-9274 was orally administered at 25 and 100 mg/kg twice a day for 5 days/week to Caki-1 (VHL-wildtype RCC) and 786-O subcutaneous nude mouse xenograft models. In these studies the tumor growth rate was attenuated at both doses in the 786-O cells and at the higher dose for Caki-1 cells. There was no obvious change in the health of any of the animals suggesting manageable tolerability. We are currently evaluating combination therapy in our laboratory. In summary, PAK4 inhibitors show considerable promise as novel treatments of RCC as a single agent and warrant further investigation. Citation Format: Omran Abu Aboud, William Senapedis, Yosef Landesman, Erkan Baloglu, Robert H. Weiss. Inhibition of PAK4 attenuates renal cell carcinoma (RCC) 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 2644. doi:10.1158/1538-7445.AM2015-2644
Risk of Venous Thromboembolism in Hematological Malignancies: The Scandinavian Thrombosis and Cancer Cohort
Authors: Inger Lise Gade, Sigrid K Brækkan, Inger Anne Næss, John-Bjarne Hansen, Frits Rosendaal, Suzanne C Cannegieter, Kim Overvad, Hilde Jensvoll, Jens Hammerstrøm, Kristine Blix, Anne Tjønneland, Søren R Kristensen, Marianne Tang Severinsen
Journal: Blood (2015)