tbuckley/cabot-search huggingface dataset:
Abstract LB-075: The histone demethylase JMJD1A is essential to prostate cancer cells through regulation of c-Myc expression
Authors: Lingling Fan, Guihong Peng, Natasha Sahgal, Ladan Fazli, Martin Gleave, Yuji Zhang, Arif Hussain, Jianfei Qi
Journal: Cancer Research (2015)

Abstract Histone demethylase JMJD1A controls gene expression by epigenetic regulation of H3K9 methylation marks. To investigate role of JMJD1A in the development and progression of prostate cancer, we knock down JMJD1A in prostate cancer cells and examine its effect on gene expression and cancer cell biology. We find that silencing of JMJD1A results in the lethality of prostate cancer cells concomitant with inhibition of cell proliferation, induction of apoptosis and cell cycle arrest. Profiling array analyses reveal c-Myc as one of the top transcriptional networks altered upon the JMJD1A inhibition. The gene ontology pathway analyses show that the primary functions of c-Myc targets regulated by JMJD1A are related to cell cycle, cell proliferation and cell survival. Mechanistically, JMJD1A promotes the recruitment of AR and induces demethylation at the c-Myc gene enhancer, thereby increasing the AR-dependent transcription of c-Myc mRNA. In a parallel pathway, JMJD1A binds to E3 ubiquitin ligase HUWE1, attenuates the HUWE1-induced degradation of c-Myc, and thus increases the c-Myc protein level. Together, JMJD1A controls the expression of c-Myc at transcriptional and post-translational levels. Re-expression of c-Myc in the JMJD1A-knockdown cells partly recues the growth of prostate cancer cells in vitro and in vivo. The protein level of c-Myc is positively correlated with that of JMJD1A in a subset of human prostate cancer specimens. Collectively, our findings identify a critical role of JMJD1A for the viability of prostate cancer cells through regulation of c-Myc expression. Note: This abstract was not presented at the meeting. Citation Format: Lingling Fan, Guihong Peng, Natasha Sahgal, Ladan Fazli, Martin Gleave, Yuji Zhang, Arif Hussain, Jianfei Qi. The histone demethylase JMJD1A is essential to prostate cancer cells through regulation of c-Myc expression. [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-075. doi:10.1158/1538-7445.AM2015-LB-075
Abstract 4494: Physical and metabolic stability of SH7139, a new drug candidate for non-Hodgkin's lymphoma targeting HLA-DR10
Authors: Rod Balhorn, Saphon Hok, Monique Cosman Balhorn
Journal: Cancer Research (2015)

Abstract Oncology drugs must remain sufficiently stable during storage, following formulation, after introduction into the bloodstream and during their entry into cells to ensure accurate dosing. After uptake by cells, the biologically active form of the drug also needs to remain stable long enough to achieve an optimal anti-tumor response. SH7139, our most advanced small molecule therapeutic for non-Hodgkin's lymphoma, was designed to target and bind to a unique site on HLA-DR10, a cell surface receptor found on B-cell lymphocytes and over-expressed on many B-cell derived malignancies. Previous studies conducted with lymphoma and other cell lines have shown that SH7139 binds selectively and is highly cytotoxic only to tumor cells expressing HLA-DR10. SH7139 has also been shown to be highly effective in treating human Burkitt's lymphoma (Raji) in a mouse xenograft model. All of the studies performed to date suggest SH7139 meets the necessary stability requirements. No degradation of the drug has been observed during storage at -20°C over a period of 30 months. SH7139 is also stable when dissolved in water or saline over a wide range of pH (pH 2 to 9). Instability is only observed at a highly alkaline pH. At pH 12, a slow auto-catalytic cleavage reaction releases a fragment of one of the recognition elements. The amide bonds linking the three recognition elements to the lysine and miniPEG scaffold of SH7139 remain stable in plasma. Hepatocytes metabolize SH7139 at a moderate rate and produce two primary metabolites. The same metabolites are produced by both canine and human hepatocytes, and the smaller product, 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxyaniline, is rapidly glucuronidated to facilitate its excretion. Both the physical and metabolic stability of SH7139 are consistent with the drug's observed anti-lymphoma activity. This research was supported by the National Cancer Institute Phase II SBIR award R44CA159843-02 to SHAL Technologies Inc. Part of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. Citation Format: Rod Balhorn, Saphon Hok, Monique Cosman Balhorn. Physical and metabolic stability of SH7139, a new drug candidate for non-Hodgkin's lymphoma targeting HLA-DR10. [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 4494. doi:10.1158/1538-7445.AM2015-4494
Abstract 2713: Stem cell mutagenesis and carcinogenesis in the colon of wild type and immune compromised mice
Authors: Barry Gold, Ryan Whetstone
Journal: Cancer Research (2015)

Abstract To test the hypothesis that a role of inflammation in the etiology of cancer is associated with the production of RONS and subsequent DNA damage, we determined the mutation frequency (MF) in colonic stem cells in C57Bl/6 mice exposed to dextran sulfate sodium (DSS), an inflammatory agent that is used in combination with azoxymethane (AOM) to produce colon tumors in mice. AOM produces promutagenic O6-methylguanine lesions in DNA but does not induce colon tumors in C57Bl/6 mice as a single agent. The MF's in the untreated and DSS treated WT and TCRβ-/- mice were &amp;lt;10-5 indicating that DSS and subsequent inflammation does not generate stem cell mutations in mice that are WT for DNA repair. AOM yielded mutant crypts in WT and TCRβ-/- mice with MF's of ∼4×10-4 and 2×10-4, respectively, which represents a statistically significance decrease in the MF in the immune compromised mice. These results suggest enhanced survival of AOM damaged stem cells in WT vs. TCRβ-/- mice. The combined treatment of AOM+DSS afforded fully mutated crypts in both strains but with a lower MF than observed with AOM alone indicating that DSS induced inflammation destroyed pre-existing AOM mutated crypts. Using the MF in WT mice, the efficiency for the conversion of an O6-methylguanine lesion into a stem cell mutation was estimated to be 0.03%. The carcinogenicity of AOM and/or DSS was evaluated in WT, TCRβ-/-, TCRδ-/- and TCRβ-/-TCRδ-/- mice. At lower DSS exposure (1.5%), there was a significant reduction in tumor incidence, multiplicity and tumor progression in the TCRβ-/- and TCRβ-/-TCRδ-/- vs. WT B6 mice. However, at higher DSS concentration (2%) the difference between the mouse strains disappeared because of an increase in the TCR null mice without a concomitant increase in the WT mice. Citation Format: Barry Gold, Ryan Whetstone. Stem cell mutagenesis and carcinogenesis in the colon of wild type and immune compromised mice. [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 2713. doi:10.1158/1538-7445.AM2015-2713
Discovery of Novel Recurrent Mutations in Childhood Early T-Cell Precursor Acute Lymphoblastic Leukemia by Whole Genome Sequencing - a Report From the St Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project
Authors: Jinghui Zhang, Li Ding, Linda Holmfeldt, Gang Wu, Susan L. Heatley, Debbie Payne-Turner, John Easton, Xiang Chen, Jianmin Wang, Michael Rusch, Charles Lu, Shann-Ching Chen, Racquel Collins-Underwood, Jing Ma, Kathryn G. Roberts, Stanley Pounds, Lei Wei, Anatoly Ulyanov, Jared Becksfort, Pankaj Gupta, Robert Huether, Richard Kriwacki, Daniel McGoldrick, David Zhao, Daniel Alford, Stephen Espy, Kiran Chand Bobba, Guangchun Song, Deqing Pei, Cheng Cheng, Stefan Roberts, Michael Barbato, Dario Campana, Elaine Coustan-Smith, William E. Evans, Sheila A Shurtleff, Maria Kleppe, Jan Cools, Kristin Shimano, Michelle L. Hermiston, Sergei Doulatov, Kolja Eppert, Elisa Laurenti, Faiyaz Notta, John E Dick, Giuseppe Basso, Stephen P. Hunger, Mignon L Loh, Meenakshi Devidas, Brent L. Wood, Stuart S. Winter, Kimberly Dunsmore, Robert S. Fulton, Lucinda A. Fulton, Xin Hong, Christopher C. Harris, David J. Dooling, Kerri Ochoa, Kimberly J Johnson, John C Obenauer, Ching-Hon Pui, Susana C. Raimondi, Clayton W Naeve, Timothy J Ley, Elaine R Mardis, Richard K Wilson, James R Downing, Charles G Mullighan
Journal: Blood (2011)
New-Onset Seizure in Adults and Adolescents
Authors: Jay R. Gavvala, Stephan U. Schuele
Journal: JAMA (2016)

<h3>Importance</h3> Approximately 8% to 10% of the population will experience a seizure during their lifetime. Only about 2% to 3% of patients go on to develop epilepsy. Understanding the underlying etiology leading to an accurate diagnosis is necessary to ensure appropriate treatment and that patients with low risk for recurrence are not treated unnecessarily. <h3>Observations</h3> Patients can present with new-onset seizure for a variety of reasons such as acute symptomatic seizures due to acute brain injury or metabolic derangements, or unprovoked seizures that are the initial manifestation of epilepsy. A patient history and physical examination may identify features more consistent with an epileptic event and laboratory studies and brain imaging can identify an acute insult contributing to the presentation. Patients diagnosed with first-time unprovoked seizure require electroencephalography and epilepsy protocol–specific magnetic resonance imaging of the brain, which includes thin-cut coronal slices to determine risk of recurrence and the need for long-term treatment. In patients who meet the criteria for diagnosis of epilepsy, a carefully selected antiepileptic medication with consideration of comorbidities, adverse effect profile, and type of epilepsy is essential along with appropriate counseling. <h3>Conclusions and Relevance</h3> Approximately 3% of the population will develop epilepsy but 2 to 3 times as many patients will experience a single seizure or seizure-like event. A diagnosis of epilepsy has significant medical, social, and emotional consequences. A careful patient history and physical examination, electroencephalography, and brain imaging are necessary to separate patients with acute symptomatic seizures, single unprovoked seizures, and nonepileptic events from those with new-onset epilepsy.
Sniffing out significant “Pee values”: genome wide association study of asparagus anosmia
Authors: Sarah C Markt, Elizabeth Nuttall, Constance Turman, Jennifer Sinnott, Eric B Rimm, Ethan Ecsedy, Robert H Unger, Katja Fall, Stephen Finn, Majken K Jensen, Jennifer R Rider, Peter Kraft, Lorelei A Mucci
Journal: BMJ (2016)

To determine the inherited factors associated with the ability to smell asparagus metabolites in urine. Genome wide association study. Nurses' Health Study and Health Professionals Follow-up Study cohorts. 6909 men and women of European-American descent with available genetic data from genome wide association studies. Participants were characterized as asparagus smellers if they strongly agreed with the prompt "after eating asparagus, you notice a strong characteristic odor in your urine," and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values <5×10-8 were considered as genome wide significant. 58.0% of men (n=1449/2500) and 61.5% of women (n=2712/4409) had anosmia. 871 single nucleotide polymorphisms reached genome wide significance for asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553. A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing.
Imatinib Is Safe and Effective In Patients with Refractory Chronic Graft Versus Host Disease: Analysis of Two Consecutive Prospective GITMO* Studies.*Gruppo Italiano Trapianto Midollo Osseo
Authors: Attilio Olivieri, Michele Cimminiello, Franco Locatelli, Marco Zecca, Paolo Corradini, Francesca Patriarca, Nicola Mordini, Pasquale Iacopino, Amedea Donelli, Carmine Selleri, Manuela Badiali, Giovanna Lucchini, Guido Gini, Pietro Leoni, Alberto Bosi, Andrea Bacigalupo
Journal: Blood (2010)
CHOP Followed by Radiotherapy for Localized Aggressive Primary Gastric Lymphoma: Results of a Multi Center Phase II Study.
Authors: Yeon Hee Park, Won Seog Kim, Baek-Yeol Ryoo, Sung Hyun Yang, Mi Sook Kim, Seung-Sook Lee, Kihyun Kim, Keon Woo Park, Chul W. Jung, Yong Chan Ahn, Do Hoon Lim, Young H. Ko, Keunchil Park
Journal: Blood (2004)
Final Report of a Phase II Study of 5-Azacitidine and Vorinostat in Patients (pts) with Newly Diagnosed Myelodysplastic Syndrome (MDS) or Acute Myelogenous Leukemia (AML) Not Eligible for Clinical Trials Because Poor Performance and Presence of Other Comorbidities
Authors: Guillermo Garcia-Manero, Elihu H Estey, Elias Jabbour, Gautam Borthakur, Tapan Kadia, Kiran Naqvi, Ross L Levine, Zeev Estrov, Alfonso Quintas-Cardama, Marina Konopleva, Stefan Faderl, Maria Tanaka, Hui Yang, Farhad Ravandi, William G. Wierda, Jorge E. Cortes, Patricia Ann Boone, Hagop M. Kantarjian
Journal: Blood (2011)
Myeloproliferative Neoplasm with BCR-JAK2 Fusion Gene As the Result of t(9;22)(p24,11.2) in a Brazilian Patient
Authors: Daniela Ferreira Dias, Marcelo Bellesso, Rodrigo Santucci, Renata Campos Elias, Veronica Ramos Oliveira, Renato Centrone, Adelson Alves
Journal: Blood (2012)
A Study of the Expression of the LMP1 Oncoprotein in Low-Grade B Cell Lymphomas and Correlation with the Levels of Oxidative Stress
Authors: Panagiotis Theodorou Diamantopoulos, Vasiliki Papadopoulou, Aikaterini Polonyfi, Athanasios G. Galanopoulos, Fani Kalala, Konstantinos Zervakis, Theodoros Iliakis, Evangelos Terpos, Despoina Perrea, Nora-Athina Viniou
Journal: Blood (2012)
Growth Differentiation Factor 15 as a Novel Biomarker for Metformin
Authors: Hertzel C. Gerstein, Guillaume Pare, Sibylle Hess, Rebecca J. Ford, Jennifer Sjaarda, Kripa Raman, Matthew McQueen, ShunFu Lee, Heinz Haenel, Gregory R. Steinberg
Journal: Diabetes Care (2016)

Metformin is a commonly used glucose-lowering drug. However, apart from glycemic measures, no biomarker for its presence or dose has been identified.A total of 237 biomarkers were assayed in baseline serum from 8,401 participants (2,317 receiving metformin) in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Regression models were used to identify biomarkers for metformin use.Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables. For the remaining 25 linked biomarkers, the odds ranged from 0.71 to 1.24. A 1.64 ng/mL higher GDF15 level predicted a 188-mg higher metformin dose (P < 0.0001).GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.
Generation of Non-Deletional Hereditary Persistence of Fetal Hemoglobin (HPFH) Beta-Yac Transgenic Mouse Models: -175 Black HPFH and -195 Brazilian HPFH
Authors: Carolina A Braghini, Fernando F Costa, Flavia C Costa, Halyna Fedosyuk, Matthew Parker, Allen M Chazelle, Kenneth R Peterson
Journal: Blood (2015)
The organization and support of clinical trials (CTs) in oncology patients through a center of clinical investigations, optimization, standardization, and safety (CIO) team.
Authors: U. Kohlweyer, S. Rohdenburg, H. Reinhardt, R. Zurheiden, V. Schmidt, M. Burbeck, M. M. Engelhardt
Journal: Journal of Clinical Oncology (2011)

e16610 Background: Clinical trials (CTs) are broadly performed due to enormous drug advances and medical progress, making the logistics of phase I-III CTs, a daily challenge. Methods: We report of our organization, structure and support of CTs and safe agent/chemotherapy-application through our departmental CIO-team. Results: Our CIO is responsible for 1. all CTs conducted within our department, 2. the documentation of in- and out-patients using an electronic tumor documentation system (eTBD) and 3. chemotherapy-logistics. In close cooperation with the attendings/PIs, our CIO-office coordinates: first contacts (e.g. with sponsors, CROs, ethics committees), evaluation of exciting CTs, trials' logistics and CRF-documentation. In order to estimate highly realistic patient recruitment numbers, we employ our eTBD which includes our patients' demographics, comorbidities, chemotherapy-pretreatment, SAEs, date of progression and survival. Almost 21.000 cancer patients are recorded within our eTBD since 1997. At least 500 detailed analyses for CT-logistics are performed per year. Another useful CT-support tool is our protocol study and review board, that organizes newly proposed CTs with our clinical and CIO-team, intensively discussing pro and cons of planned CTs, feasibility questions and logistics. Within CTs, close collaborations have been proven valuable, e.g. with collaborating departments, translational research teams, clinical pharmacy and European approval offices. In order to enhance patient recruitment into CTs, we employ intranet-based trial synopses. Entity-specific 'CT-out-patient-clinics' are another useful tool to efficiently enrol patients into CTs. The quality management (QM) committee has repeatedly demonstrated our patients' and sponsors' utmost satisfaction to our described efforts. For our achievements, the CIO has won the 2009-QM prize of our university and was finalist of the Golden Helix Award 2010. Conclusions: In times of increasingly dense physicians' schedules and with enormous CT-logistics, our CIO structure is highly valuable for successful trial performance.
MGN1703, a Novel TLR9-Agonist - Results of a Phase 1 Clinical Trial in Patients with Metastatic Malignancies.
Authors: Martin R Weihrauch, Manuel Schmidt, Marina Tschaika, Heike Richly, Michael S von Bergwelt-Baildon, Ulrich Hacker, Alexander Shimabokuro-Vornhagen, Burghardt Wittig, Max E Scheulen
Journal: Blood (2009)
Fertility preservation options and the young breast cancer patient: A survey.
Authors: Manuela Jacobsen Junqueira, Shari Beth Goldfarb, Bridget A. Oppong, Sujata Patil, Anne Eaton, Cristina Olcese, Jessica Morgan, Joanne Frankel Kelvin, Maura N. Dickler, Mary Gemignani
Journal: Journal of Clinical Oncology (2012)

575 Background: Approximately 15% of breast cancers (BC) are diagnosed in reproductive aged women. Management of the disease in this age group frequently includes chemotherapy and hormonal therapy, which can both affect fertility. Considering that age at first delivery has been steadily increasing, young women may face BC before completion of childbearing. Methods: In this prospective study, women referred to our institution for surgical treatment of BC were asked, before their first visit, to fill out a questionnaire regarding their reproductive history and fertility preservation knowledge. Eligible patients included women between the ages of 18 and 45, with a newly diagnosed BC, who had not yet started treatment. Results: Sixty women were eligible with a median age of 40 (range 20-45). 98% of responders (59 out of 60) had been diagnosed within the previous 2 months. 78% (47/60) had a college or post-graduate degree. 80% (48/60) had been pregnant before, while 86.5% (45/52) reported having had children. 81% (47/58) were premenopausal, and only 3 patients reported not having had periods for more than 1 year. 50% of responders (30/60) declared no interest in future childbearing, 25% were definitely interested, and 25% were undecided. However, only 9% (5/57) reported having received information on fertility preservation options before the survey. Women who have been pregnant were significantly less likely to consider fertility preservation options prior to treatment (egg/embryo/ovarian tissue cryopreservation [6% vs. 50%, p=0.001]), or after treatment (egg/embryo donation, surrogacy or adoption [6% vs. 58%, p&lt;0.0001]). Conclusions: This pilot study was designed to gather information on reproductive health of newly diagnosed young BC patients and to assess their willingness to consider various fertility preservation options before or after treatment. Our study population consisted of mostly women who had been pregnant and had children. We found that 50% of the women were unsure or wanted future children. Yet, only 9% had received information on fertility options at diagnosis. This pilot study highlights the need for education and/or intervention in fertility preservation options for young women with breast cancer.
Abstract 5016: Short-term blockade of EGF signaling improves immune-mediated cytotoxicity of NSCLC cells
Authors: Charli Dominguez
Journal: Cancer Research (2015)

Abstract One of the manifestations of tumor plasticity is the acquisition of mesenchymal-like features by epithelial tumor cells via the phenomenon of epithelial-mesenchymal transition (EMT). This phenotypic conversion of tumor cells is known to be associated with tumor resistance to multiple cancer therapies, including chemotherapy, radiation and some small molecule-targeted therapies. Recent work from our group demonstrated that tumor cells undergoing the EMT may also become resistant to immune-mediated cytotoxicity involving antigen-specific and innate effector cells. As signaling through the epidermal growth factor receptor (EGFR) is a major inducer of EMT in epithelial cells, in the present study we sought to investigate the effect of short-term EGFR inhibition with erlotinib on tumor phenotype, and provide rationale for combination with immune-mediated therapies. Our data shows that pretreatment with the EGFR TKI erlotinib for less than 72 hours modulates tumor plasticity and immune-mediated cytotoxicity in NSCLCs harboring a sensitizing EGFR mutation. A significant modulation in expression of multiple EMT markers can be observed, including significant changes in the levels of expression of the transcription factor brachyury, a driver of human tumor EMT and a target for immunotherapeutic interventions. In addition, significant modulation of immune-relevant molecules on the surface of tumor cells can be observed, including changes in the levels of TRAIL-receptors, co-stimulatory and checkpoint molecules. The observed phenotypic changes in response to short-term erlotinib treatment correlate with an enhancement of immune-mediated tumor cell lysis, without any observed adverse affect on effector cell populations. Taking into account that brachyury-based cancer vaccines are currently being evaluated in clinical trials, modulation of brachyury levels and the observed enhancement of immune-mediated lysis in erlotinib-treated tumors may provide the rationale for future combinations of erlotinib and brachyury-based vaccines for the treatment of lung carcinomas. Citation Format: Charli Dominguez. Short-term blockade of EGF signaling improves immune-mediated cytotoxicity of NSCLC 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 5016. doi:10.1158/1538-7445.AM2015-5016