tbuckley/cabot-search huggingface dataset:
Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL
Authors: Justyna A. Wierzbinska, Reka Toth, Naveed Ishaque, Karsten Rippe, Jan-Philipp Mallm, Lara C. Klett, Daniel Mertens, Thorsten Zenz, Thomas Hielscher, Marc Seifert, Ralf Küppers, Yassen Assenov, Pavlo Lutsik, Stephan Stilgenbauer, Philipp M. Roessner, Martina Seiffert, John Byrd, Christopher C. Oakes, Christoph Plass, Daniel B. Lipka
Journal: Genome Medicine (2020)

Abstract Background In cancer, normal epigenetic patterns are disturbed and contribute to gene expression changes, disease onset, and progression. The cancer epigenome is composed of the epigenetic patterns present in the tumor-initiating cell at the time of transformation, and the tumor-specific epigenetic alterations that are acquired during tumor initiation and progression. The precise dissection of these two components of the tumor epigenome will facilitate a better understanding of the biological mechanisms underlying malignant transformation. Chronic lymphocytic leukemia (CLL) originates from differentiating B cells, which undergo extensive epigenetic programming. This poses the challenge to precisely determine the epigenomic ground state of the cell-of-origin in order to identify CLL-specific epigenetic aberrations. Methods We developed a linear regression model, methylome-based cell-of-origin modeling (Methyl-COOM), to map the cell-of-origin for individual CLL patients based on the continuum of epigenomic changes during normal B cell differentiation. Results Methyl-COOM accurately maps the cell-of-origin of CLL and identifies CLL-specific aberrant DNA methylation events that are not confounded by physiologic epigenetic B cell programming. Furthermore, Methyl-COOM unmasks abnormal action of transcription factors, altered super-enhancer activities, and aberrant transcript expression in CLL. Among the aberrantly regulated transcripts were many genes that have previously been implicated in T cell biology. Flow cytometry analysis of these markers confirmed their aberrant expression on malignant B cells at the protein level. Conclusions Methyl-COOM analysis of CLL identified disease-specific aberrant gene regulation. The aberrantly expressed genes identified in this study might play a role in immune-evasion in CLL and might serve as novel targets for immunotherapy approaches. In summary, we propose a novel framework for in silico modeling of reference DNA methylomes and for the identification of cancer-specific epigenetic changes, a concept that can be broadly applied to other human malignancies.
NON-INVASIVE ELECTROANATOMIC MAPPING TO PREDICT ORIGIN OF OUTFLOW TRACT VENTRICULAR PREMATURE DEPOLARIZATIONS
Authors: Kristie Coleman, Stavros Mountantonakis, Aditi Vaishnav, Parth Makker, Moussa Saleh, Kabir Bhasin, Neil Bernstein, Nicholas Skipitaris
Journal: Journal of the American College of Cardiology (2020)
Meeting the Educational Needs of an Increasingly Diverse Surgical Workforce
Authors: Minerva A. Romero Arenas
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
THE IMPACT OF CORONARY ARTERY DISEASE ON ATRIAL FIBRILLATION RECURRENCE AFTER ABLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Pablo Paz, Barbara Mantilla, Saif El Nawaa, M Rubayat Rahman, Mohamed Elmassry, Pattara Rattanawong, Prapaipan Putthapiban, Ty Whisenant, Jakrin Kewcharoen, Wasawat Vutthikraivit
Journal: Journal of the American College of Cardiology (2020)
Prevalence of Pathogenic Variants in Cancer Susceptibility Genes Among Women With Postmenopausal Breast Cancer
Authors: Allison W. Kurian, Ryan Bernhisel, Katie Larson, Jennifer L. Caswell-Jin, Aladdin H. Shadyab, Heather Ochs-Balcom, Marcia L. Stefanick
Journal: JAMA (2020)

This study uses Women’s Health Initiative data to compare the prevalence of pathogenic variants (PVs) in breast cancer susceptibility genes in postmenopausal women with vs without breast cancer to guide decisions about who should undergo PV testing.
Recurrent IDH mutations in high-grade meningioma
Authors: Corey M Gill, Joshua Loewenstern, John W Rutland, Hanane Arib, Nancy Francoeur, Ying-Chih Wang, Nataly Fishman, Margaret Pain, Melissa Umphlett, Yayoi Kinoshita, Russell B McBride, Joshua Bederson, Michael Donovan, Melissa Smith, Robert Sebra, Raj K Shrivastava, Mary Fowkes
Journal: Neuro-Oncology (2020)
NON-CRITICAL CARE TELEMETRY MONITORING FOR NON-CARDIAC RELATED DIAGNOSES: A TIMELY FOLLOW-UP
Authors: Suren Visvanathan, Jonathan Finkel, Sandeep Sharma, Himani Pulivarthi, Purna Sharma, Kumar Ashish, Taranjit Gill, Aishwarya Kuchikulla
Journal: Journal of the American College of Cardiology (2020)
Managing Virtual Hybrid Psychiatrist-Patient Relationships in a Digital World
Authors: Jay H. Shore
Journal: JAMA Psychiatry (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
VARIABILITY OF DISCHARGE MEDICAL THERAPY FOR SECONDARY PREVENTION AMONG PATIENTS WITH MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES (MINOCA) IN THE UNITED STATES
Authors: Harmony R. Reynolds, Rachel Dubner, Nathaniel Rosso Smilowitz, Anne Hellkamp, Robert Jay Widmer
Journal: Journal of the American College of Cardiology (2020)
HEART FAILURE POST-DISCHARGE TELEMONITORING IN A SAFETY-NET HOSPITAL REDUCES 30-DAY READMISSIONS
Authors: Pranay Prabhakar, Vincent Carter, Mohammed Merchant, Ahmed Alsalem, Benson Ku, Aubrey Grant, Courtney Bess, Diane Wirth, Modele Ogunniyi
Journal: Journal of the American College of Cardiology (2020)
Point mutation in p14ARF-specific exon 1Beta of CDKN2A causing familial melanoma and astrocytoma (Research Letter)
Authors: Aideen McInerney-Leo, Lawrie Wheeler, Richard Sturm, Jean-Marie Tan, Jessica Harris, Lisa Anderson, Kasturee Jagirdar, Matt Brown, Paul Leo, H. Peter Soyer, Emma Duncan
Journal: British Journal of Dermatology (2018)

Research letter Dear Editor, Rarely, melanoma is dominantly inherited, with CDKN2A mutations accounting for > 85% of mutation‐positive families.1 CDKN2A encodes two, nonhomologous proteins, p16 and p14ARF, with individually unique first exons (1α and 1β, respectively) and alternative reading frames. Over 95% of the CDKN2A mutations in familial melanoma occur in the p16 transcript...
LOW VISIT ADHERENCE IN A NONCOMMUNICABLE DISEASE CLINIC IN RURAL HAITI
Authors: Lily Yan, Benito Isaac, Kayleigh Bhangdia, Waking Jean-Baptiste, Densa Belony, Louine Martineau, Serge Vertilus, Dufens Pierre-Louis, Darius Fenelon, Emelia Benjamin, Lisa Hirschhorn, Gene Bukhman, Gene Kwan
Journal: Journal of the American College of Cardiology (2020)
PULMONARY ARTERY PRESSURE MONITORING EFFECTIVELY GUIDES MANAGEMENT TO REDUCE HEART FAILURE HOSPITALIZATIONS IN PATIENTS WITH OBESITY
Authors: Douglas Marshall Brinkley, Maya Guglin, Mosi Bennett, Margaret M. Redfield, William Abraham, Marie-Elena Brett, Nicholas Dirckx, Philip B. Adamson, Lynne Stevenson
Journal: Journal of the American College of Cardiology (2020)
The cost-effectiveness of transarterial chemoembolization treatments.
Authors: Fadia T. Shaya, Ian Michael Breunig, Nader Hanna, Viktor Chirikov, Brian S. Seal, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2012)

e14626 Background: Transarterial chemoembolization (TACE) is often a treatment for patients precluded from surgery. TACE recipients may get ≥1 TACE treatment, yet little is known about the cost-effectiveness of such additional TACEs. Methods: The study population includes 1,095 Medicare patients with a 1st diagnosis of 1ry HCC in 2000-07 who got TACE, or both TACE+ablation (LD) where one occurred prior to any other treatments. Patients were studied through end of 2009, in SEER-Medicare A-B. Stratifying by ablation, Cox proportional hazards models were built to assess the impacts of successive TACEs on all-cause/HCC-mortality, adjusting for clinical (cancer stage, underlying health status, liver conditions) and demographics. Average HCC-related Medicare costs (US$2,011) attributed to additional TACEs was estimated with generalized least squares, obtaining incremental cost effectiveness ratios (ICERs) and 95% confidence intervals, controlling for systemic chemotherapy and radiation therapy in the follow-up period. Results: Cancer stages 1, 2, 3, and 4 represented 34%, 16%, 19%, and 5% of the 1095 patients, respectively: 26% unstaged, 68% male, 71% Caucasian, 6% African American, and 17% Hispanic. 474 non-LD TACE patients had one TACE, 218 two, 93 three, 70 ≥four. Among LD patients, 121 got 1 TACE, 58 two, 34 three, 27 ≥four. In non-LD patients, further reductions in all-cause/HCC mortality were associated with the 2nd (HR .76, p&lt;.01; HR .78, p=.045) and 3rd (HR .68, p&lt;.01; HR .61, p&lt;.01) TACE, but not the 4th; only the 3rd TACE further reduced mortality risk in LD patients (HR .48, p=.01; HR .34, p .01). For non-LD patients, using HCC mortality, the 2nd TACE was attributed to $19,969 per life year (LY) added, 95%CI $8,634, $31,303, the 3rd $10,290/LY ($2,815, $17,764); using all-cause mortality, the 2nd $27,813/LY ($15,943, $39,684), the 3rd ICER was statistically N.S. All ICERs were N.S. for LD patients. Conclusions: Additional TACEs provide survival benefit for HCC Medicare patients in clinical practice. However, that benefit may decrease after the 3rd exposure, which is more cost effective than a 2nd one. Additional TACEs may be confounded if ≥4 TACEs are intended to treat biologically aggressive disease.
LEFT ATRIAL HYPERTENSION AND THE RISK OF RECURRENT HEART FAILURE AFTER ATRIAL FIBRILLATION ABLATION
Authors: Jasen Lee Gilge, Asim Ahmed, Bradley Clark, Benzy Padanilam, Jeffrey Olson, Girish Venugopalan Nair, Sandeep Joshi, Ashwin Kumar Ravichandran, Parin Patel
Journal: Journal of the American College of Cardiology (2020)
GREY-ZONE TROPONIN AND THE RISK FOR POOR OUTCOME AMONG HOSPITALIZED PATIENTS UNDERGOING MYOCARDIAL PERFUSION IMAGING
Authors: Anat Berkovitch, Alexey Naimushin, Nir Shlomo, Shlomi Matetzky, Roy Beigel, Michael Naroditsky, Elad Asher, Eli Rozen, Ilan Goldenberg, Robert Klempfner, Ronen Goldkorn
Journal: Journal of the American College of Cardiology (2020)
VALIDATION OF CHADS2, CHA2DS2VASC AND R2CHA2DS2VASC SCORES FOR PREDICTING STROKE ONE YEAR AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Paul Muutu Ndunda, Peter Tadros, Mark Wiley, George Zorn, Gregory Muehlebach, Heyrettin Okut, Mohinder Vindhyal, Zaher Fanari
Journal: Journal of the American College of Cardiology (2020)
THE NARROW YET NOT SO NARROW VENTRICULAR TACHYCARDIA
Authors: Sangeeta Prabhakar Bhat, Wilson Young, Hamza Hafeez, Sharath Rajagopalan, Najam Saqib, Muhammad Pir, Abdul Haseeb, Mirza Mujadil Ahmad, Pranjal Boruah
Journal: Journal of the American College of Cardiology (2020)
PLATYPNEA-ORTHODEOXIA SYNDROME IN A PATIENT WITH COR TRIATRIATUM DEXTER AND PATENT FORAMEN OVALE: A CASE REPORT
Authors: Sravani Lokineni, Bassil Said, Venkata Satish Pendela, Erfan Alotaki, Depta Jeremiah, Bipul Baibhav
Journal: Journal of the American College of Cardiology (2020)
THE IMPACT OF THE AFFORDABLE CARE ACT ON DISPARITIES IN UTILIZATION OF CARDIOVASCULAR PREVENTIVE SERVICES BY SOCIOECONOMIC STATUS
Authors: Hannah Verma, Jonathan Hong, Shiwani Mahajan, Nihar R. Desai, Salim Virani, Harlan Krumholz, Harlan Krumholz, Khurram Nasir, Javier Valero Elizondo
Journal: Journal of the American College of Cardiology (2020)
Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders
Authors: Dennis Lal, Patrick May, Eduardo Perez-Palma, Kaitlin E. Samocha, Jack A. Kosmicki, Elise B. Robinson, Rikke S. Møller, Roland Krause, Peter Nürnberg, Sarah Weckhuysen, Peter De Jonghe, Renzo Guerrini, Lisa M. Niestroj, Juliana Du, Carla Marini, James S. Ware, Mitja Kurki, Padhraig Gormley, Sha Tang, Sitao Wu, Saskia Biskup, Annapurna Poduri, Bernd A. Neubauer, Bobby P. C. Koeleman, Katherine L. Helbig, Yvonne G. Weber, Ingo Helbig, Amit R. Majithia, Aarno Palotie, Mark J. Daly
Journal: Genome Medicine (2020)

Abstract Background Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes belong to gene families. The use of gene family information for disease gene discovery and variant interpretation has not yet been investigated on a genome-wide scale. We empirically evaluate whether paralog-conserved or non-conserved sites in human gene families are important in NDDs. Methods Gene family information was collected from Ensembl. Paralog-conserved sites were defined based on paralog sequence alignments; 10,068 NDD patients and 2078 controls were statistically evaluated for de novo variant burden in gene families. Results We demonstrate that disease-associated missense variants are enriched at paralog-conserved sites across all disease groups and inheritance models tested. We developed a gene family de novo enrichment framework that identified 43 exome-wide enriched gene families including 98 de novo variant carrying genes in NDD patients of which 28 represent novel candidate genes for NDD which are brain expressed and under evolutionary constraint. Conclusion This study represents the first method to incorporate gene family information into a statistical framework to interpret variant data for NDDs and to discover new NDD-associated genes.
DOBUTAMINE STRESS ECHOCARDIOGRAM (DSE) INDUCED TAKOTSUBO SYNDROME: A RARE COMPLICATION OF A COMMON NON-INVASIVE DIAGNOSTIC TEST
Authors: Priyanka Parajuli, Manjari Regmi, Odalys Estefania Lara-Garcia, Debra Doud, Arvind Garg, Ish Singla
Journal: Journal of the American College of Cardiology (2020)
Post-transplant lymphoproliferative disorder (PTLD) after liver transplantation: Report of 16 cases from a single center.
Authors: Ayhan Ulusakarya, Beatrice Delmas Marsalet, Srimanta Misra, Nahla Cucherousset, Philippe Ichai, Mazen Haydar, Watek Almohamad, Yusuf Gumus, Hamid Bessaoud, Pasquale Innominato, Emma Goldschmidt, Didier Samuel, Catherine Guettier, David Machover, Ali Turhan, Jean-Francois Morere
Journal: Journal of Clinical Oncology (2013)

e19513 Background: PTLD is a rare complication of organ transplantation, but it can jeopardize the transplantation outcome. Methods: Paul Brousse University Hospital is the largest liver transplantation center in France. We retrospectively analyzed data from all of the patients who experienced PTLD and treated in our hematology/oncology department in the last 10 years. Results: 16 cases of PTLD occurred after various intervals following the liver transplant without correlation with the type of underlying liver disease or immunosuppressive treatment. Overall, the patients had poor general health (ECOG 3-4: 69%), renal and/or hepatic failure (75%), and cytopenia (63%). PTLD were often of high grade (81%), B phenotype (94%), stage IV (75%), with high LDH (88%). The most frequent disease sites were liver (63%), subdiaphragmatic lymphadenopathy (69%), and extranodal (69%). After a reduction in the immunosuppressive treatment, the patients received their initial chemotherapy mostly with a combination of prednisolone, cyclophosphamide, vincristine, and rituximab. As soon as their general condition improved, R-CHOP was given as the standard regimen. All patients experienced severe and frequent complications during chemotherapy. Two patients had liver transplant rejection, lethal in one case. Six patients died: 4 of progression or relapse of PTLD, one after 4 th liver transplantation, one of leukoencephalitis. Complete remission was obtained in 81% of patients. Ten patients (63%) are alive in complete remission after a median follow up of 6.5 years. Conclusions: Despite the clinical complexity of these patients, PTLD can be treated utilizing common lymphoma chemotherapy with treatment accommodations to poor ECOG, liver and renal dysfunctions.
Incidental Breast Carcinoma Detected With 13N-NH3 Cardiac PET Imaging
Authors: Marie Louise E. Bernsen, Friso M. van der Zant, Maurits Wondergem, Wouter A. M. Broos, Remco J. J. Knol
Journal: Clinical Nuclear Medicine (2020)

A 78-year-old woman with chest pain and a history of pacemaker implantation for arrhythmia underwent myocardial perfusion imaging by means of N-NH3 cardiac PET/CT. N-NH3 cardiac PET showed no signs of ischemia or infarction. Incidentally, a nodule with increased N-NH3 activity was observed in the right breast. Histopathologic examination revealed invasive ductal carcinoma.
NICE recommends migraine drug that could treat 10 000 patients in England
Authors: Elisabeth Mahase
Journal: BMJ (2020)

A drug to prevent chronic migraine could soon become available on the NHS for around 10 000 people in England, after the National Institute for Health and Care Excellence (NICE) found it to be cost effective.

In its draft guidance on the drug NICE has recommended fremanezumab (Ajovy, Teva Pharmaceuticals), citing clinical trial evidence presented by the manufacturer, which found that the drug reduced the number of monthly migraine days more than placebo for episodic and chronic migraine. …
COMPREHENSIVE IN VIVO CORONARY PLAQUE MAPPING: A 3-VESSEL OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Makoto Araki, Tsunenari Soeda, Hyung Oh Kim, Vikas Thondapu, Michele Russo, Osamu Kurihara, Hiroki Shinohara, Yoshiyasu Minami, Takumi Higuma, Taishi Yonetsu, Tsunekazu Kakuta, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2020)
PROGNOSTIC VALUE OF RIGHT VENTRICULAR BRANCHES SLOW FLOW PHENOMENON AFTER PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE CORONARY SYNDROME IN THE RIGHT CORONARY ARTERY
Authors: Koshi Setoyama, Shinjo Sonoda, Yutaro Naka, Hiroki Okabe, Konosuke Inoue, Toshiya Miura, Reo Anai, Yuki Tsuda, Masaru Araki, Yutaka Otsuji
Journal: Journal of the American College of Cardiology (2020)
CATHETER ABLATION OF ATRIAL FIBRILLATION IN HEART FAILURE PATIENTS WITH OR WITHOUT OTHER ETIOLOGIES
Authors: Giichi Nitta, Osamu Inaba, Junichi Nitta, Yohei Tamura, Gaku Narita, Hirotaka Yano, Shunichi Kato, Toshikazu Kono, Takashi Ikenouchi, Kazuya Murata, Yasuaki Hada, Miki Kanoh, Tomomasa Takamiya, Yukihiro Inamura, Ken Negi, Akira Sato, Tsunehiro Yamato, Yutaka Matsumura, Masahiko Goya, Tetsuo Sasano
Journal: Journal of the American College of Cardiology (2020)
Evaluation of food effect on pharmacokinetics (PK) of GDC-0449 (G) in advanced solid tumor patients.
Authors: Manish Sharma, Soonmo Peter Kang, Theodore Karrison, Kehua Wu, Michelle Turcich, David Geary, Naoko Takebe, Richard A. Graham, Michael L. Maitland, Richard L. Schilsky, Mark J. Ratain, Ezra E. W. Cohen
Journal: Journal of Clinical Oncology (2012)

e13106 Background: GDC-0449 (Vismodegib, Genentech), an orally bioavailable small-molecule SMO (Smoothened) inhibitor, was recently approved for advanced basal cell carcinoma (BCC) and is being evaluated in other solid tumors. This study sought to determine whether there is a significant effect of food on the PK of G. Methods: In part I, patients (pts) were randomized 1:1 to fasting overnight (FO) or a high fat meal (HF) before a single dose of G 150 mg. The study was later amended to 1:1:2 randomization to FO, HF or a low fat meal (LF). Plasma concentrations of G were determined by a validated liquid chromatography-tandem mass spectrometry assay. PK endpoints were observed Cmax, observed Tmax, and AUC (0-24 and 0-168 hours). In part II, pts randomized to FO or HF in part I took G 150 mg/day in a fasting state, while pts randomized to LF took G 150 mg/day in a fed state. PK endpoints after two weeks were steady state (ss) Cmax, ss Tmax, and ss AUC (0-24 hours). 60 pts enrolled 10/09-11/11, of which 43 were evaluable for PK: 18 FO; 14 HF; 11 LF. Pt characteristics: Female 53%; median age 59; PS 0: 62%, 1: 38%. Tumor types: 43% colorectal; 17% pancreatic; 40% other. Results: PK data were log-transformed for analysis. AUC (0-168 hours) after a single dose was higher in HF than in FO pts (p = 0.049); ratio of geometric means = 1.46 (90% CI = 1.07-1.99). There was a trend toward higher Cmax after a single dose in HF than in FO pts (p = 0.071); ratio of geometric means = 1.39 (90% CI = 1.03-1.88). There were no significant differences between groups for single dose AUC (0-24 hours) and Tmax. There were no significant differences between fasting and fed groups for ss Cmax, ss Tmax, or ss AUC (0-24 hours). The frequencies of drug-related Grade ≥ 3 toxicities were similar in the fasting and fed groups. There were no objective responses; 11 pts (18%) had stable disease for a median duration of 16 weeks and a maximum of 104 weeks (BCC). Conclusions: A high fat meal increases plasma exposure to a single dose of G, but there are no significant PK or safety differences between fasting and fed groups at ss. GDC-0449 can be taken with or without food for daily dosing. This study design is an efficient way to evaluate the effect of food on oral anti-cancer drugs. Supported by NCI grant 5U01-CA69852-12.