tbuckley/cabot-search huggingface dataset:
Abstract 2096: High sensitivity of cutaneous T-cell lymphoma (CTCL) to CABE, a component of propolis
Authors: Arumugam Jayakumar, Radjendirane Venugopal, Rafal Zielinski, Aleksandra Rusin, Izabela Fokt, Stanislaw Skora, Xiao Ni, Madeleine Duvic, Waldemar Priebe
Journal: Cancer Research (2015)

Abstract Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of diseases characterized by clonal expansion of malignant T-cells in the skin. In the course of our quest to screen and identify a potent, selective anti-proliferative drug for CTCL, we discovered that caffeic acid benzyl ester (CABE), a natural component of edible plant species found in high concentrations in propolis, showed increased potency for CTCL (IC50 4 μM) in vitro compared to other tumor types such as melanoma (IC50 25 μM), glioma (IC50 25 μM), multiple myeloma (MM) (IC50 70 μM), head and neck squamous cell carcinoma (HNSCC) (IC50 25 μM), ovarian cancer (OC) (IC50 17 μM), breast carcinoma (IC50 43 μM), and Hodgkin's B-cell lymphoma (IC50 33 μM). Cell death in CTCL MJ and HH cell lines was accompanied by increased caspase-3 and poly (ADP-ribose) (PARP) cleavage and annexin V staining. There is growing evidence that CABE and its analogs exert their anticancer activity by modulating expression level of key transcription factors. Here, we evaluated the effects of CABE on the activity of different transcription factors and the expression of total and phosphorylated proteins in MJ cells by use of the transcription factor activation profiling array (TFAPA) and the reverese-phase protein array profiling (RPPA) assays. The activity of 48 transcription factors (TFs) and expression of 225 unique total and phosphorylated proteins could be monitored simultaneously by using a collection of biotin-labeled DNA probes and 225 unique antibodies. TFAPA analysis revealed that 18 TFs (including STAT1, STAT4, and RXR) were up-regulated and 3 TFs (STAT3, STAT5, and SATB1) were down-regulated to a variable extent in cells treated with 10 μM CABE for 5 h as compared to vehicle-treated control. RPPA analysis revealed 41 differentially expressed proteins between vehicle control and cells treated with 10 μM CABE. These can be functionally categorized into functional groups: DNA repair, cell cycle, apoptosis, phosphoinositide 3-kinase (PI3K)/AKT/mTOR, and receptor kinase pathways. Our results suggest that CABE targets multiple signaling pathways in CTCL in vitro, warranting the development of a pre-clinical animal model for the testing of CABE efficacy in vivo. Acknowledgement: These studies were supported in part by the grant from Moleculin, LLC Citation Format: Arumugam Jayakumar, Radjendirane Venugopal, Rafal Zielinski, Aleksandra Rusin, Izabela Fokt, Stanislaw Skora, Xiao Ni, Madeleine Duvic, Waldemar Priebe. High sensitivity of cutaneous T-cell lymphoma (CTCL) to CABE, a component of propolis. [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 2096. doi:10.1158/1538-7445.AM2015-2096
Correlation of Peripheral Blood Involvement Measured by Four-Color Flow Cytometry and the Achievement of Molecular Response in Mantle Cell Lymphoma Treated within the Prospectively Randomized Intergroup Trials of the European MCL Network
Authors: Christiane Pott, Sebastian Boettcher, Stefan Gesk, Reiner Siebert, Wolfram Klapper, Eva Hoster, Matthias Ritgen, Michael Unterhalt, Marietta Rottenkolber, Wolfgang Hiddemann, Michael Kneba, Martin Dreyling
Journal: Blood (2007)
BH3-Mimetics, ABT-737 and Obatoclax, Work Synergistically to Induce Cell Death In Leukemic Cell Lines
Authors: Grace Shimin Koh, Nan Jiang, Di Feng Dong, Joshua Yew Suang Lim, Shirley Kow Yin Kham, Fook Tim Chew, Lim Soon Wong, Allen Yeoh
Journal: Blood (2010)
OC-008 Virtual inflammatory bowel disease clinics in the real world
Authors: J Hunter, S James, D Chan, B Stacey, M Stroud, P Patel, F Cummings, D Fine
Journal: Gut (2010)

<h3>Introduction</h3> The follow-up of IBD patients is challenging due to the relapsing remitting nature of the diseases, the wide spectrum of severity and complexity as well as the need for monitoring of long-term complications and drugs. Conventional outpatient follow-up lacks flexibility for patients and there are competing pressures for clinic time such as 18-week targets, follow-up appointment waiting times, new patient to follow-up ratios and increasing demand. Alternatives to conventional outpatient follow-up include telephone clinics, self-management programmes or discharging patients. The IBD Virtual Clinic (VC) is an effective alternative model. Patients with an established diagnosis for &gt;2 years, who have been stable for &gt;1 year, do not have PSC and are agreeable are entered into the VC system. Two months before their annual follow-up is due a blood test form, simple questionnaire and information sheet are sent to the patient. If they meet any of the criteria on the questionnaire they are asked to contact the IBD specialist nursing team to discuss their condition. The blood test results, patient9s database entry and case notes are reviewed to ensure that they are not due colonoscopic surveillance, DEXA scanning etc. The patient and their GP are sent a letter informing them of the blood test results and management plan. <h3>Methods</h3> The VC database was reviewed to assess the effectiveness of the service. 127 patients were asked to complete an on-line or postal satisfaction survey on their VC experience. <h3>Results</h3> Between 2006 and 2009 306 patients with UC and 177 with CD have been added to the VC. In the period 2006–2008 79 patients required an out-patient appointment for a flare, 9 were admitted, 7 had abnormal blood tests and 12 DNAed follow-up. An estimated 866 outpatient appointments have been saved. 66% of patients responded to the survey. 9.1% of patients preferred conventional outpatient follow-up while 87.6% felt their condition was adequately monitored using the VC. 88.9% of employed patients felt that due to the VC their condition interfered less with their work while 71.8% of all patients felt their condition interfered less with their family/social life. 26.6% of patients found it difficult to get bloods tested at their GPs. 92% and 86.6% of patients who contacted the flare line and non-urgent advice line, respectively were satisfied with the service. Flare patients were seen within a mean of 5.3 days and 92% of non-urgent messages responded to within 2 days. <h3>Conclusion</h3> This is an innovative, efficient, patient responsive method for following up patients with stable IBD. Benefits include a reduction in new:follow-up clinic ratios, increased outpatient capacity to see flare patients and a reduction in secondary care visits for patients. In addition it meets the IBD Standards for follow-up of patients. The model has now been applied to coeliac disease and Barrett9s oesophagus.
Insulin-Like Growth Factor II Is an Autocrine Growth Factor To Prevent Apoptosis as Well as To Enhance Proliferation and Maturation of Erythroid Progenitor Cells.
Authors: Taro Nagatomo, Koichiro Muta, Shouichi Ohga, Masayuki Ochiai, Shunji Hikino, Toshiro Hara
Journal: Blood (2005)
Immunological Effects and Predictive Gene Signatures in Patients with Relapsed Follicular Lymphoma Treated with CT-011, a Humanized Anti-PD-1 Monoclonal Antibody
Authors: Fuliang Chu, Jason R. Westin, Min Zhang, Lei Feng, Veerabhadran Baladandayuthapani, Zhiqiang Wang, Rochelle Allen, Michael Wallace, Luis Vence, Laszlo Radvanyi, Larry W. Kwak, Rinat Rotem-Yehudar, R Eric Davis, Sattva S. Neelapu
Journal: Blood (2012)
Abstract 2126: Comprehensive transcriptome analysis reveals that nonsense-mediated mRNA decay is not globally suppressed in lung adenocarcinomas
Authors: Xiangyin Kong
Journal: Cancer Research (2015)

Abstract As a well-known mRNA surveillance mechanism, the nonsense-mediated mRNA decay (NMD) pathway ensures the rapid degradation of mRNAs containing premature termination codons (PTC). Prior research has shown that features of the tumor microenvironment, such as hypoxia and amino acid deprivation, might inhibit NMD activity. However, a systemic analysis of NMD in cancer is seldom performed. Rather than focusing on only a few NMD targets and using artificial interventions as in previous experiments, we aimed to analyze NMD in cancer from a global perspective. By analyzing lung Adenocarcinomas in detail, we observed comparable decay efficiencies in tumors for both annotated and predicted NMD targets. Interestingly, the expression patterns of key NMD factors are altered, indicating that cancer cells might prefer to use different NMD degradation pathways. We also identified a subset of NMD targets with unique manners in either tumor or adjacent tissues. Besides, our analyses further demonstrate that the NMD efficiencies vary across tumors, supporting the heterozygosity of lung Adenocarcinomas. Citation Format: Xiangyin Kong. Comprehensive transcriptome analysis reveals that nonsense-mediated mRNA decay is not globally suppressed in lung adenocarcinomas. [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 2126. doi:10.1158/1538-7445.AM2015-2126
Abstract 2829: Discovery and in vitro and in vivo characterization of aminopyrazoline-based SMYD2 inhibitors
Authors: Carlo Stresemann, Ingo Hartung, Timo Stellfeld, Naomi Barak, Jeffrey Mowat, Clara Christ, Antonius ter Laak, Silke Koehr, Jörg Weiske, Roman Hillig, Volker Badock, Detlef Stoeckigt, Karl Ziegelbauer, Hilmar Weinmann, Volker Gekeler
Journal: Cancer Research (2015)

Abstract SMYD2 (SET and MYND domain-containing protein 2) is a protein lysine methyltransferase (PKMT) which was initially described as a histone H3K36 and H3K4 methyltransferase involved in transcriptional regulation. SMYD2 has recently been reported to methylate and regulate several non-histone cancer relevant proteins such as p53, retinoblastoma protein (Rb) and the estrogen receptor alpha. Given the reports that overexpression of SMYD2 is linked to poor prognosis in certain cancers, SMYD2 is proposed to be an oncogene and an attractive cancer drug target. Here we report the discovery of a novel potent and selective SMYD2 inhibitor, SMYD2-BAY-01, by high throughput screening and extensive biophysical validation. The co-crystal structure revealed that SMYD2-BAY-01 binds to the substrate binding site and occupies the hydrophobic pocket for lysine binding using an unprecedented hydrogen bond pattern. The competitive behavior of the inhibitor in biochemical assays is consistent with the binding mode observed in the crystal structure. Further optimization generated SMYD2-BAY-02, which shows improved low nanomolar potency and is selective against kinases and other PKMTs. Furthermore, SMYD2-BAY-02 specifically inhibits SMYD2 methylation activity in a cellular assay with similar potency and reduces methylation of the tumor suppressor protein p53. Based on promising in vitro and in vivo DMPK data, SMYD2-BAY-02 was further characterized in vivo for SMYD2-specific methylation inhibition. In vivo activity could be shown upon in vivo administration at doses as low as 30 mg/kg p.o. in a SMYD2 overexpressing esophageal squamous cell carcinoma model. In summary, SMYD2-BAY-02 is a promising selective and potent SMYD2 inhibitor in vitro and in vivo and may represent a new treatment option for cancers overexpressing SMYD2. Citation Format: Carlo Stresemann, Ingo Hartung, Timo Stellfeld, Naomi Barak, Jeffrey Mowat, Clara Christ, Antonius ter Laak, Silke Koehr, Jörg Weiske, Roman Hillig, Volker Badock, Detlef Stoeckigt, Karl Ziegelbauer, Hilmar Weinmann, Volker Gekeler. Discovery and in vitro and in vivo characterization of aminopyrazoline-based SMYD2 inhibitors. [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 2829. doi:10.1158/1538-7445.AM2015-2829
A BCR-ABL1-Like Gene Expression Profile Confers a Poor Prognosis In Patients with High-Risk Acute Lymphoblastic Leukemia (HR-ALL): A Report From Children's Oncology Group (COG) AALL0232
Authors: Mignon L Loh, Richard C. Harvey, Charles G Mullighan, Stephen B. Linda, Meenakshi Devidas, Michael J. Borowitz, Andrew J. Carroll, I-Ming Chen, Julie M. Gastier-Foster, Nyla A. Heerema, Huining Kang, Elizabeth A. Raetz, Kathryn G. Roberts, Jinghui Zhang, Naomi Winick, Brent L. Wood, Eric C. Larsen, William L. Carroll, Cheryl L Willman, Stephen P Hunger
Journal: Blood (2011)
BOTH MD Anderson Cancer Center MODEL and German Score Work in Predicting Time to First Treatment in EARLY Chronic Lymphocytic Leukemia: Results of an External Validation Analysis
Authors: Stefano Molica, Diana Giannarelli, Massimo Gentile, Giovanna Cutrona, Nicola Di Renzo, Francesco Di Raimondo, Antonino Neri, Massimo Federico, Manlio Ferrarini, Fortunato Morabito
Journal: Blood (2012)
168. Assaying Hepatic Correction Mediated by Varied AAV Vectors in a Knock-Out Transgenic Mouse Model of Methylmalonic Acidemia (MMA)
Authors: Brandon T. Hubbard, Randy J. Chandler, Charles P. Venditti
Journal: Molecular Therapy (2016)

Methylmalonic acidemia (MMA) is an inborn error of metabolism most commonly caused by deficient methylmalonyl-CoA mutase (MUT) activity. The disorder can have multiple clinical manifestations, including metabolic instability, stroke of the basal ganglia, pancreatitis, end-stage renal failure, growth impairment, osteoporosis and developmental delay. Unfortunately, current non-invasive therapies fail to chronically manage the disease, and patients still suffer from increased morbidity and early mortality. Solid organ transplantation, including elective liver, combined liver-kidney and isolated kidney transplantation, has been used to provide sustained benefit to patients, but the procedures come with substantial risks as well as the post-operative requirement for life-long immunosuppression. To address the large and unmet need for new therapies for patients with MMA, we have developed an effective adeno-associated viral (AAV) gene therapy that has been previously validated in a neonatal lethal mouse model of Mut deficiency (Mut−/−). The current project compares how two distinct AAV8 vectors that express the human MUT gene under the control of either the liver specific, human alpha 1-antitrypsin (hAAT) promoter, or the ubiquitous CMV-enhanced chicken β-actin (CBA) promoter differentially affect metabolite levels following systemic delivery to adult mice. The animals used in this study (Mut−/−;TgINS-MCK-Mut) express wild-type Mut in a muscle-specific fashion via a stable germline transgene and completely lack transgene expression in the liver. Mut−/−;TgINS-MCK-Mut) mice accurately model the hepatorenal manifestations of MMA, but afford an opportunity to assess gene therapy vectors at or after weaning because mice are rescued from neonatal lethality, yet experience massive elevations of the characteristic metabolites (methylmalonic and 2-methylcitric acid) because of the lack of hepatic Mut activity. Disease related metabolites were measured in plasma samples derived from Mut−/−; TglNS-MCK-Mut mice (n=7) prior to AAV gene delivery. The mice were then injected via the retro-orbital route with 1.5X1011 GC of either AAV8-hAAT-MUT or AAV8-CBA-MUT. At 10 days and 30 days post-treatment, mice treated with either vector showed a significant reduction in methylcitrate and methymalonic acid levels, with AAV8-CBA-MUT (n=2) treated mice manifesting methylcitrate and methylmalonic acid levels that trended lower than those measured in mice injected with AAV8-hAAT-MUT (n=4) at both time points. Further studies will be needed to precisely compare the differences between the hAAT and CBA promoters in MMA mouse models, but our preliminary results demonstrate that the Mut−/−; TgINS-MCK-Mut mice can be used to easily ascertain hepatic correction of Mut deficiency, which should help inform the selection of regulatory elements that will provide maximal therapeutic efficacy to treat patients with MMA.
TNFRSF14 and EZH2 Mutations, Chr2p Gain and Copy Number Changes Targeting Genes Whose Proteins Interact with the Microenvironment In Transformed Follicular Lymphoma
Authors: David Wrench, Ajanthah Sangaralingam, Hira Tayyib, Myung-Kuk Kang, Ciaran O'Riain, Manu Gupta, Emanuela Carlotti, Csaba Bodor, Sameena Iqbal, Tracy Chaplin, Janet Matthews, Andrew James Clear, Andrew Davies, Silvia Montoto, Maria Calaminici, Bryan D Young, John G. Gribben, Andrew Lister, Jude Fitzgibbon
Journal: Blood (2010)
Familiar Chronic Myeloproliferative Syndromes in First-Degree Relatives and Monozygotic Twins.
Authors: Stefano Pulini, Serena Rupoli, Gaia Goteri, Angela Tassetti, Anna Rita Scortechini, Simonetta Mulattieri, Andrea Stronati, Giuseppe Saglio, Pietro Leoni
Journal: Blood (2006)
681. HIV-1 Mediated Insertional Activation of STAT5B and BACH2 Promotes the Formation of a Viral Reservoir in T Regulatory Cells
Authors: Daniela Cesana, Francesca R. Santoni de Sio, Laura Rudilosso, Pierangela Gallina, Andrea Calabria, Laura Passerini, Silvia Nozza, Elisa Vicenzi, Guido Poli, Silvia Gregori, Giuseppe Tambussi, Eugenio Montini
Journal: Molecular Therapy (2016)

Since its identification, HIV-1 remains a global health threat responsible for a world-wide pandemic. The introduction of Anti-Retroviral Therapy (ART) greatly extended patients survival; however ART can control but not cure HIV infection. It has been recently suggested that HIV-1 by integrating near cancer-associated genes could promote the expansion and persistence of infected cells in patients under ART. However, the molecular mechanism/s of insertional mutagenesis used and the physiological impact on the cells harboring these integrations are completely unknown.Here, we found that in peripheral blood mononuclear cells (PBMC) from 54 HIV-1 infected patients under ART, BACH2 and STAT5B were targeted by a significantly higher number of integrations and with the same orientation of gene transcription compared to other lentiviral integration (LV) datasets (p<0.0001). Furthermore, aberrant chimeric transcripts containing viral sequences fused to the first protein coding exon of BACH2 or STAT5B and predicted to encode for unaltered full-length proteins were found in PBMC of 34% (30/87) of HIV-1 patients under ART. Tracking the expression of HIV-1/STAT5B and HIV/BACH2 transcripts by droplet digital PCR in T cell subpopulations purified from the blood of patients under ART (N=6), we found a significant enrichment (higher than 10 fold) of the chimeric mRNAs in T-regulatory cells in all patients tested. The absence of any reported cases of T cell leukemia induced by HIV insertions in patients (despite several years of infection) and the role of these transcription factors suggest that cell clones harboring this type of activating insertions acquire a selective advantage possibly by altering the T-cell identity and/or homeostasis rather than triggering cell transformation. In vitro experiments performed on T regulatory cells purified from healthy donors demonstrated that the LV-mediated expression of these transcription factors significantly increased their proliferation ability (p<0.001) without impacting on their immune-suppressive function. Overall, our findings provide novel evidences that HIV-1 takes advantage of insertional mutagenesis to favor its persistence in the host by activating STAT5B and BACH2. Indeed, the HIV-mediated deregulation of these transcription factors could confer a selective advantage to T regulatory cells, which being able to diminish the immune surveillance against infected cells contribute to promote long-term viral persistence. Hence, new targeted therapies aimed at interfering with BACH2 and STAT5B regulated pathways could provide the general means for the immunological re-sensitization towards HIV-1 infected cells to reduce long lived cellular reservoirs and the eradication of the viral infection in HIV-1 patients.
Prognostic Factors of Response and Survival in CMML Patients Treated with Azacitidine (AZA)
Authors: Lionel Ades, Mikkael A. Sekeres, Alice Wolfromm, Melissa L. Teichman, Ramon V. Tiu, Raphael Itzykson, Jaroslaw P. Maciejewski, Francois Dreyfus, Alan F. List, Pierre Fenaux, Rami S. Komrokji
Journal: Blood (2011)
Staging with 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for nonseminomatous germ cell tumor (NSGCT): The Peter MacCallum Cancer Centre experience
Authors: C. J. Pezaro, G. C. Toner, R. Hicks
Journal: Journal of Clinical Oncology (2009)

e16140 Background: We retrospectively evaluated our single institution experience using FDG-PET as part of initial assessment of stage I/II NSGCT. Previous studies by de Wit et al and the TE22 trial concluded that there was a very limited role for PET staging in NSGCT. Despite these results, PET continues to be utilised in our center. Methods: With local ethics approval, the PET center database at Peter MacCallum Cancer Centre (PMCC) was used to identify a series of 26 patients with NSGCT who underwent FDG-PET as part of staging investigations between 1998 and 2008. Demographic and clinical information was collected using electronic and paper medical records. Histological samples were reviewed if additional information was required. Results: Lymphovascular invasion (LVI) was present in 10 (38%) of orchiectomy specimens. 15 patients had stage I disease on both CT and PET. PET upstaged 7 patients from stage I to stage II disease, and all upstaged patients received systemic chemotherapy (3 cycles BEP). 1 patient with stage I disease on PET and CT received adjuvant chemotherapy (2 cycles EP). 3 patients with LVI and stage 1 disease on CT and PET underwent surveillance. With median follow-up of 33 months (range 1–94), all patients were alive without disease recurrence, although 1 patient was treated for a second primary NSGCT. Conclusions: Using PET images, we were able to identify patients with low volume metastatic disease and achieve 100% relapse-free survival rates. Despite the small sample size, these results are promising and are better than expected based on published data. This might be explained by the quality of the PET imaging, including attenuation correction and combined CT/PET for enhanced sensitivity interpreting retroperitoneal disease. Further evaluation of PET is warranted, particularly in patients with equivocal CTs or with the high-risk feature of LVI. [Table: see text] No significant financial relationships to disclose.