tbuckley/cabot-search huggingface dataset:
Decreased Incidence of Osteonecrosis of the Jaw (ONJ) in Patients with Multiple Myeloma (MM) Treated with Zoledronic Acid (ZA) after Application of Preventive Measures.
Authors: Meletios Athanasios Dimopoulos, Efstathios Kastritis, Christina Bamia, Ioannis Melakopoulos, Dimitra Gika, Maria Roussou, Magdalini Migkou, Evangelos Eleutherakis-Papaiakovou, Aristotle Bamias
Journal: Blood (2007)
Adjuvant FOLFOX +/− cetuximab in fullRAS andBRAF wildtype stage III colon cancer patients
Authors: J. Taieb, R. Balogoun, K. Le Malicot, J. Tabernero, E. Mini, G. Folprecht, J.-L. Van Laethem, J.-F. Emile, C. Mulot, S. Fratté, C.-B. Levaché, L. Saban-Roche, J. Thaler, L.N. Petersen, J. Bridgewater, G. Perkins, C. Lepage, E. Van Cutsem, A. Zaanan, P. Laurent-Puig
Journal: Annals of Oncology (2016)
Quantification of the Active Decitabine-Triphosphate (DAC-TP) Metabolite: A Novel Pharmacoanalytical Endpoint for Optimization of Hypomethylating Therapy in Acute Myeloid Leukemia (AML)
Authors: Hongyan Wang, Ping Chen, Jiang Wang, Ramasamy Santhanam, Josephine Aimiuwu, Vijayasaradhi UV, Zhongfa Liu, Sebastian Schwind, Alice S. Mims, Rebecca B Klisovic, Alison Walker, Michael R. Grever, Miguel Villalona-Calero, John C. Byrd, Ramiro Garzon, William Blum, Kenneth K. Chan, Guido Marcucci
Journal: Blood (2012)
Abstract 747: Glutamine, glutaminase and γ-glutamyl-transferase activities are essential for lung tumorigenesis
Authors: Daniel R. Sappington, Eric R. Siegel, Rosalind B. Penney, Gunnar Boysen
Journal: Cancer Research (2015)

Abstract Increased glutamine uptake has been found to drive cancer cell proliferation, making tumor cells glutamine-dependent or even addicted. Glutamine is believed to provide additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, a pathway known to be activated in tumor cells. Additionally, glutathione concentrations are known to be elevated in non-small cell lung cancer (NSCLC) and is believed to protect against oxidative stress. In contrast, glutathione's participation in the γ-glutamyl-cycle is less well studied. Here we investigated the hypothesis that glutamine drives glutathione synthesis and export, drives the γ-glutamyl-cycle, and thereby contributes to NSCLC tumor cell proliferation. Glutamine consumption and glutathione excretion were measured in H460, A549 and MRC-5 cell lines. Treatment with BPTES, a known GLS inhibitor, led to reduced cell proliferation. This was also demonstrated when γ-glutamyl-transferase (GGT) was inhibited with acivicin. GGT transfers glutamyl groups from glutathione to amino acids to facilitate the amino acid transport into the cell. These results suggest active utilization of the γ-glutamyl cycle in the tumor cells. The formation of metabolites downstream of GLS and GGT were essentially abolished at the lowest inhibitor concentrations studied. In contrast, biological endpoints, such as MTT assay response, required up to 30-fold higher inhibitor concentrations. Culturing in stable isotope-labeled glutamine demonstrated that &amp;gt;50% of excreted glutathione and &amp;gt;80% of γ-glutamyl amino acids were derived from glutamine. Together these results demonstrate that glutamine is actively utilized for synthesis and excretion of glutathione which, in turn, is utilized to promote amino acid uptake by the formation of γ-glutamyl amino acids. These findings add yet another important function to the glutamine dependence of tumor cells. In addition to providing TCA cycle intermediates, we show that glutamine promotes glutathione synthesis to increase cellular defense mechanisms, and drives the γ-glutamyl cycle to enhance amino acid uptake. Citation Format: Daniel R. Sappington, Eric R. Siegel, Rosalind B. Penney, Gunnar Boysen. Glutamine, glutaminase and γ-glutamyl-transferase activities are essential for lung tumorigenesis. [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 747. doi:10.1158/1538-7445.AM2015-747
Translational In Vivo and In Vitro Studies in Patients (pts) with Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML) and Myeloproliferative Disease (MPD) Treated with MK-0457 (MK), a Novel Aurora Kinase, Flt3, JAK2, and Bcr-Abl Inhibitor.
Authors: Raoul Tibes, Francis Giles, Teresa McQueen, Donald A. Bergstrom, Steven J. Freedman, Michael Andreeff
Journal: Blood (2006)
AICAR Induces Apoptosis in Chronic Lymphocytic Leukemia Cells through the Mitochondrial Pathway and Independently of p53 Pathway and AMPK Activation.
Authors: Joan Gil, Antonio F Santidrián, Diana M González-Gironès, Daniel Iglesias-Serret, Llorenç Coll-Mulet, Ana M Cosialls, Mercè de Frias, Clara Campàs, Eva González-Barca, Esther Alonso, Alberto Fernandez de Sevilla, Benoit Viollet, Gabriel Pons
Journal: Blood (2009)
Impact of Molecular Genetics on Disease-Free Survival in Myelofibrosis Patients Following Allogeneic Stem Cell Transplantation
Authors: Nicolaus Kroeger, Victoria Panagiota, Tatjana Zabelina, Michelle Maria Araujo Cruz, Rabia Shahswar, Anita Badbaran, Ioanna N Triviai, Francis Ayuk, Marten Gehlhaar, Christine Wolschke, Robin Bollin, Ulrich Lehmann, Christian Koenecke, Anuhar Chaturvedi, Haefaa Alchalby, Michael Stadler, Matthias Eder, Maximilian Christopeit, Gudrun Göhring, Michael Koenigsmann, Brigitte Schlegelberger, Hans Heinrich Kreipe, Arnold Ganser, Boris Fehse, Felicitas Thol, Michael Heuser
Journal: Blood (2015)
A Multicentre Trial of the Effectiveness of ζ Globin Enzyme Linked Immunosorbent Assay (ELISA) and Hb H Inclusion Body Screening for the Detection of α Thalassemia Trait.
Authors: John D. Lafferty, David S. Barth, Brian L. Sheridan, Andrew G. McFarlane, Linda M. Halchuk, Mark A. Crowther
Journal: Blood (2006)
KIT blockade is sufficient for donor hematopoietic stem cell engraftment in Fanconi anemia mice
Authors: Shanmuganathan Chandrakasan, Rajeswari Jayavaradhan, John Ernst, Archana Shrestha, Anastacia Loberg, Phillip Dexheimer, Michael Jordan, Qishen Pang, Bruce Aronow, Punam Malik
Journal: Blood (2016)
Human immunodeficiency virus–infected and uninfected adults with non–genotype 3 hepatitis C virus have less hepatic steatosis than adults with neither infection
Authors: Jennifer C. Price, Yifei Ma, Rebecca Scherzer, Natalie Korn, Kyle Tillinghast, Marion G. Peters, Susan M. Noworolski, Phyllis C. Tien
Journal: Hepatology (2016)

Hepatic steatosis (HS) is common in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, but the independent contributions of HCV and HIV to HS are unclear. Magnetic resonance imaging and spectroscopy were used to measure visceral adipose tissue (VAT) and liver fat fraction (LFF) (total lipids/[total lipids + water]) in 356 adults: 57 with HCV monoinfection, 70 with HIV/HCV coinfection, 122 with HIV monoinfection, and 107 with neither infection. Participants who were infected with HCV genotype 3 were excluded because of the genotype's reported steatogenic effects. For prevalence estimates, HS was defined as LFF ≥ 0.05. We estimated the association of HIV and HCV status with LFF using multivariable linear regression, adjusting for demographics, lifestyle, and metabolic factors including the homeostasis model assessment estimate of insulin resistance (HOMA‐IR) and liver fibrosis defined using the aspartate aminotransferase‐to‐platelet ratio index (APRI). The prevalence of HS was highest in the uninfected (33%) and HIV‐monoinfected (28%), followed by the HCV‐monoinfected (19%) and HIV/HCV‐coinfected (11%) ( P = 0.003 across groups). Compared with uninfected participants—and after adjusting for demographics, lifestyle, and metabolic factors—HIV monoinfection, HCV monoinfection, and HIV/HCV coinfection were associated with 19% (95% confidence interval [CI], −39% to 6%), 38% (95% CI, −55% to −12%), and 42% (95% CI, −59% to −18%) lower LFF, respectively. HCV monoinfection and HIV/HCV coinfection remained strongly associated with lower LFF after further adjusting for APRI, and results were unchanged after excluding subjects with suspected cirrhosis. Among the entire cohort, Hispanic ethnicity, male sex, VAT, and HOMA‐IR were independently associated with greater LFF. Conclusion : Contrary to expectations, HIV/HCV‐coinfected and HCV‐monoinfected adults had significantly less liver fat than uninfected adults, even after adjusting for demographics, lifestyle, metabolic factors, and hepatic fibrosis. Our findings suggest that non–genotype 3 HCV infection may be protective against HS. The mechanisms by which this occurs and the impact of HCV treatment on HS requires further investigation. (H epatology 2017;65:853‐863)
Abstract 1872: Plasma carotenoids and breast cancer risk in the Cancer Prevention Study II Nutrition Cohort
Authors: Ying Wang, Susan M. Gapstur, Mia M. Gaudet, Jeremy D. Furtado, Hannia Campos, Marjorie L. McCullough
Journal: Cancer Research (2015)

Abstract Background: Several plasma carotenoids have been inversely associated with postmenopausal breast cancer risk in large cohort studies and a pooled analysis. Whether associations differ by tumor or participant characteristics is unclear. We investigated the associations of plasma carotenoids with postmenopausal breast cancer risk overall and by estrogen receptor (ER) status, tumor stage, smoking status and body mass index in a case-control study nested in the Cancer Prevention Study II Nutrition Cohort. Methods: A total of 561 breast cancer cases diagnosed between blood draw in 1998-2001 and June 30, 2007 and matched 1:1 with controls on race, birth date and blood draw date were included. Multivariable-adjusted conditional and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Plasma α-carotene was inversely associated with breast cancer risk even after adjustment for total fruit and vegetable intake (4th vs. 1st quartile OR = 0.58, 95% CI: 0.40, 0.85, P-trend = 0.03). This inverse association was stronger among ever smokers (P-interaction&amp;lt;0.05), and obese women (P-interaction = 0.02), but did not differ by tumor stage (P-heterogeneity = 0.61). Although there was an inverse trend between α-carotene and ER+ (P-trend = 0.01) but not ER- breast cancer (P-trend = 0.99), the test for heterogeneity by ER status was not statistically significant (P-heterogeneity = 0.28). There was some evidence of an inverse association with total carotenoids but this association was nonlinear. Conclusions: These results suggest that higher plasma α-carotene is associated with lower risk of breast cancer, and this association was even stronger in smokers and obese women. Citation Format: Ying Wang, Susan M. Gapstur, Mia M. Gaudet, Jeremy D. Furtado, Hannia Campos, Marjorie L. McCullough. Plasma carotenoids and breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. [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 1872. doi:10.1158/1538-7445.AM2015-1872
Abstract 181: miR-134 targets programmed cell death 7 (PDCD7) gene to modulate the pathogenesis of head and neck carcinoma
Authors: Shih-Yuan Peng, Kuo-Wei Chang, Shu-Chun Lin, Hsi-Feng Tu
Journal: Cancer Research (2015)

Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the prevalent malignancies in the world. microRNAs (miRNAs) are involved in the neoplastic process of various malignancies including HNSCC to mediate post-transcriptional down-regulation of target genes. This study shows that miR-134 enhances the proliferation, migration and invasion of HNSCC cells. In silico modules predict that programmed cell death 7 (PDCD7) gene could be one of the targets of miR-134. In stable HNSCC cell subclones, ectopic miR-134 expression decreased PDCD7 expression; while the ectopic miR-134Zip expression increased PDCD7 expression. Reporter assays confirmed the binding of miR-134 to the wild type 3′UTR of PDCD7, which decreased reporter activity. The targeting of miR-134 to the 3′UTR of PDCD7 was abolished by the mutations in targeted sequences. Moreover, miR-134Zip expression increased the activity of wild type reporter. Down-regulation of PDCD7 was identified in around 70% of HNSCC tumors, which was significantly opposite to miR-134 expression. A trend of reverse expression between miR-134 and PDCD7 was also present in HNSCC cell lines. PDCD7 was up-regulated following the apoptosis induced by cis-platin. Ectopic PDCD7 expression decreased the proliferation and migration of HNSCC cells, but it was unable to affect apoptosis or drug resistance status. Moreover, miR-134 associated oncogenicity was attenuated by PDCD7 expression. Taking together, this study concludes that the oncogenic potential of miR-134 in head and neck carcinoma is able to be mediated by targeting PDCD7. Citation Format: Shih-Yuan Peng, Kuo-Wei Chang, Shu-Chun Lin, Hsi-Feng Tu. miR-134 targets programmed cell death 7 (PDCD7) gene to modulate the pathogenesis of head and neck carcinoma. [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 181. doi:10.1158/1538-7445.AM2015-181
The utility of in-vivo functional and genetic parameters of drug elimination for the estimation of irinotecan (Ir) clearance (CL)
Authors: M. Michael, P. Mitchell, R. Hicks, A. Scott, A. Ellis, M. Thompson, J. Hoskins, S. Bates, N. Tebbutt, J. R. Zalcberg
Journal: Journal of Clinical Oncology (2004)

2034 Background: Dosing nomograms based upon metabolic phenotype/genotypes may reduce the marked interpatient variability in the clearance (CL) of cytotoxics in cancer patients (pts). Irinotecan (Ir) is a relevant model drug, its active moiety (SN38), undergoes glucuronidation by uridine diphosphoglucuronyl transferase (UGT)-1A1, and with its metabolites is excreted via biliary membrane transporters P glycoprotein (Pgp) and MRP. The aim of this trial was to correlate functional imaging of biliary excretion, and significant polymorphisms in the genes coding for Pgp (exons 12, 21, 26) and UGT-1A1(*28) with Ir pharmacology. Methods: Eligible pts had colorectal cancer, adequate organ function, ECOG PS 0–2. Pre-therapy all pts had bloods taken for Pgp single nucleotide polymorphism (SNP) analysis and UGT 1A1*28 carriage and underwent hepatic 99mTc-DIDA and -MIBI scans, measures of biliary MRP and Pgp function, respectively. DIDA and MIBI hepatic extraction fraction (HEF), CL, elimination half-time and % retention at 1-hr were calculated. Pts received Ir 125mg/m2/90-min, Leucovorin 20mg/m2, 5FU 500mg/m2 bolus, days 1 & 8, q 3weekly. Plasma was taken for Ir and metabolite analysis on day 1 of cycle 1, using a limited sampling model. Results: 21 pts accrued, M:F = 16:5, Mean age 61 yrs. Mean Ir CL = 14.1 L.hr-1.m-2(CV: 20%), SN38 AUC = 253.9 ng.hr.ml-1 (CV: 56%) (n= 17). Ir CL failed to correlate with either hepatic imaging mode. SN38 AUC inversely correlated with DIDA hepatic clearance (R2 = 0.36). Pts hetero- and homozygous for Pgp exon 21 and 26 SNPs demonstrated a trend to increased SN38 AUC and similarly for pts hetero- (n = 7) and homozygous (n = 2) for UGT 1A1*28. The frequency of delayed diarrhea in cycle 1 was, Grade 0/1: n = 13 pts, Grade 2: 4, Grade 3: 4. A trend to increased DIDA HEF and % retention at 1-hr and MIBI HEF in pts with grade 2/3 diarrhea was noted relative to pts with grade 0/1 diarrhea. Conclusions: Functional hepatic imaging together with Pgp and UGT polymorphisms have shown potentially useful correlates with Ir and SN38 pharmacology and with further appraisal may allow for individualised dosing of this and other relevant cytotoxics. No significant financial relationships to disclose.
681. Increasing Insulin Activity During AAV (Adeno-Associated Virus) Administration to Muscle Improves Gene Transfer in Mice
Authors: Sean M. Carrig, Enoch Bijjiga, Ashley T. Martino
Journal: Molecular Therapy (2015)

25+ years of AAV (adeno-associated virus) gene therapy research has resulted in optimized: 1- delivery routes, 2- vectors, 3- genomes and 4- immunosuppression. These studies have yielded the first westernized AAV gene therapy drug to treat LPLD (lipoprotein Lipase Deficiency) and the promise of future AAV gene therapy drugs to treat hemophilia B and other genetic disorders. Interestingly, we have little understanding of how hormones regulate these AAV drug/future drug candidates. Our studies show that hormone management has a place in improving AAV gene therapy. Since liver and skeletal muscle are strong responders to insulin and these tissues are common targets for these AAV treatments, our studies focused on how insulin regulates AAV gene therapy. We tested insulin supplementation in: HepG2 (liver), differentiated myocytes, HEK293 (kidney) and A549 (lung epithelial). HepG2 and myocytes showed elevated INSR (insulin receptor) mRNA levels (6 to 9-fold respectively) compared to HEK293 and A549 cells. The elevated INSR levels paralleled a significant 2.5 and 3 fold increase in AAV2-CMV-LacZ (M.O.I of 5e3)gene transfer to HepG2 and myocytes respectively when media was supplemented with insulin. Insulin enhanced gene transfer was not seen in HEK293 and A549 cells. Additionally, using HI glucose (4.5 g/L) and LOW glucose (1.0 g/L) medias, we showed that these results were not influenced by glucose availability. When comparing INSR levels in C57BL/6 mouse tissue, liver and skeletal muscle showed a 10-Fold and 22-Fold increase respectively compared to lung tissue. In these mice, intra-muscular (I. M.) gene delivery using AAV1-CMV-schFIX (dose: 3.0e10 v.g.) was significantly improved 4 to 5 fold (figure 1) using insulin augmentation protocols: either a subcutaneous insulin pellet which released 4 U/kg per day or a high carbohydrate (70%) diet. The insulin augmentation protocols began 1.0 hr prior to AAV administration and continued for 4 weeks after. AAV delivery occurred during the window of a significant drop (3 fold) in blood glucose indicating an increase in insulin activity. The glucose levels had returned to normal 7 days later even though the insulin augmentation protocols continued for 4 weeks likely due to antagonistic feedback responses to long-term hyperinsulinemic conditions (i.e. cortisol release). The insulin augmentation protocols only demonstrated an increase in insulin activity at the onset of vector delivery but not after, yet elevated hFIX levels were sustained throughout the study, even after the insulin augmentation protocols ended. This indicates that insulin activity does not impact sustained transgene expression and may only regulate AAV uptake, intracellular trafficking or both. Data from liver directed studies using AAV8-CMV-schFIX are pending.
MicroRNA Expression Profiling in Multiple Myeloma: Correlation with Genetic Abnormalities
Authors: Norma C. Gutiérrez, Maria Eugenia Sarasquete, Manuel Delgado, Patricia Martín-Jiménez, Carmen Chillón, Isabel M. Isidro, Teresa Prieto, Ramon García-Sanz, Jesus M. Hernández, Marcos González, Jesus F San Miguel
Journal: Blood (2008)
Gene Expression Signatures Predict Overall Survial in Diffuse Large B Cell Lymphoma Treated with Rituximab and Chop-Like Chemotherapy.
Authors: Georg Lenz, George Wright, Sandeep Dave, Alexander Kohlmann, Wenming Xiao, John Powell, Hong Zhao, Weihong Xu, Randy D. Gascoyne, Joseph M. Connors, Lorraine May, Dennis D. Weisenburger, Tim Greiner, Julie Vose, James O. Armitage, Javeed Iqbal, Martin Bast, Kai Fu, Elias Campo, Emili Montserrat, Armando Lopez-Guillermo, Pedro Jares, Antonio Martinez, Betty Gibbs, Lisa M. Rimsza, Richard I. Fisher, Rita M. Braziel, Ray Tubbs, James Cook, Brad Pohlman, John Sweetenham, Gunhild Troen, Erlend B. Smeland, Jan Delabie, Stein Kvaloy, Harald Holte, Elaine S. Jaffe, Wyndham H. Wilson, Nicole Grant, Elena Hartmann, Andreas Rosenwald, German Ott, Hans-Konrad Muller-Hermelink, T. Andrew Lister, Mickey Williams, Lothar Wieczorek, Wing C. Chan, Louis M. Staudt
Journal: Blood (2007)
PTU-038 New diagnosis of inflammatory bowel disease in the over 60s: an unintended consequence of the Bowel Cancer Screening Programme?
Authors: L PEE, A F Muller
Journal: Gut (2010)

<h3>Introduction</h3> The Bowel Cancer Screening Programme (BCSP) was introduced in England in 2006, with the expectation that screening would be available throughout England for the 60–69 years of age cohort by the end of 2009. Our own Trust began screening in May 2009. Although the programme aims is to detect individuals with polyps or tumours, patients with other causes of internal bleeding may be identified. <h3>Methods</h3> The results of all 253 patients (pts) attending for screening colonoscopy in the 6-month period May – October 2009 were assessed. The Hospital notes and pathology records were reviewed for all reports mentioning a diagnosis of inflammatory bowel disease (IBD). Pts identified with IBD were asked about pre screening colonoscopy bowel symptoms. Patients whose records indicated a known diagnosis of IBD were removed from the study. <h3>Results</h3> 15/253 pts (5.9%) were reported to have endoscopic features of inflammatory bowel disease. 5 pts were removed from the analysis on account of : prior diagnosis of Crohn9s (1), normal histology despite endoscopic evidence stating inflammation / ulceration (2) and 2 pts with ileal ulceration known to have been on anti-inflammatory drugs or aspirin. 10 pts (6M:4F, 4%) of the screening cohort were identified with a new diagnosis of Crohn9s (ileal (5) or aphthous ulceration of the colon, 2) or ulcerative colitis (3, left sided). Recommendations for Gastroenterology referral were made to the GP. One patient was started on mesalazine on the day of the procedure together with same day review by the IBD Nurse specialist. Most (9/10) of the cohort had experienced a change in bowel habit or rectal bleeding, but had not reported their symptoms to the GP. <h3>Conclusion</h3> 4% of our patient cohort attending for bowel cancer screening colonoscopy were given a new diagnosis of inflammatory bowel disease. The majority described pre-existing symptoms but had not sought medical advice, with the arrival of the faecal occult blood testing kit prompting them to participate in the programme. An unintended benefit of the BCSP has been to identify IBD in a 4% cohort of individuals attending for screening colonoscopy.