tbuckley/cabot-search huggingface dataset:
Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups
Authors: Pavel Sumazin, Yidong Chen, Lisa R. Treviño, Stephen F. Sarabia, Oliver A. Hampton, Kayuri Patel, Toni‐Ann Mistretta, Barry Zorman, Patrick Thompson, Andras Heczey, Sarah Comerford, David A. Wheeler, Murali Chintagumpala, Rebecka Meyers, Dinesh Rakheja, Milton J. Finegold, Gail Tomlinson, D. Williams Parsons, Dolores López‐Terrada
Journal: Hepatology (2016)

Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2-like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity.Analysis of immunohistochemical assays using antibodies targeting these genes in a prospective study of 35 HBs suggested that these candidate biomarkers have the potential to improve risk stratification and guide treatment decisions for HB patients at diagnosis; our results pave the way for clinical collaborative studies to validate candidate biomarkers and test their potential to improve outcome for HB patients. (Hepatology 2017;65:104-121).
Impact of adjuvant trastuzumab-based chemotherapy in T1ab node-negative HER2 overexpressing breast carcinomas.
Authors: Jean-Sebastien Frenel, Manuel Jorge Rodrigues, Julien Peron, Vano Yann-Alexandre, Johanna Wassermann, Marc Debled, Francois Picaud, Laurence Albiges, Anne Vincent-Salomon, Paul H. Cottu
Journal: Journal of Clinical Oncology (2012)

601 Background: HER2 overexpression has been recognized as a pejorative prognostic factor in node negative T1ab (T1abN0) breast tumors. Randomized clinical trials have shown benefit of adjuvant trastuzumab-based chemotherapy (ATBC) for node-positive and/or greater than 1 cm (T1c or more) HER2+ breast carcinomas. There are no prospective efficacy data of ATBC in T1abN0 HER2+ tumors. Methods: We retrospectively evaluated 276 cases of T1ab node-negative HER2+ breast tumors in 8 French Comprehensive Cancer Centers. We assessed clinical, therapeutic features and outcome. We estimated the probability of disease-free survival (DFS), analyzed associations of ATBC, patient and tumor characteristics with DFS and prognosis factors using the log-rank test, multivariate analysis with logistic regression and Cox’s proportional hazards model. Results: Out of the 276 T1abN0 cases, 129 (47%) received ATBC (ATBC+) and 123 (45%) were not treated by either trastuzumab or chemotherapy (ATBC-). Of these 252 ATBC+ or ATBC- patients, decision of ATBC was associated with date of diagnosis (before or after ASCO 2005 Annual Meeting when interim results from three trastuzumab adjuvant trials were reported) and with poor prognosis features: negative hormone receptors (HR-) status, Elston-Ellis high grade, tumor size &gt; 5 mm and age. With a median follow-up of 44 months 16 recurrences were observed (13 in the ATBC- group, 2 in the ATBC+ and 1 with adjuvant chemotherapy alone). Nine recurrences were distant metastases. A survival benefit in ATBC+ was observed with a 99% 40-months DFS versus 93% for ATBC- (logrank p-test = 0.018). In an exploratory analysis, two factors were significantly associated with worst prognosis for ATBC- that were not observed for ATBC+ : HR- status (98% 40-months DFS for ATBC+ patients versus 84% for ATBC- patients; logrank p-test = 0.0003) and presence of lymphovascular invasion (100% 40-months DFS for ATBC+ versus 73% in ATBC- cases; logrank p-test = 0.003). Conclusions: In our seriesATBC is associated with a significant reduction of risk of recurrence of T1abN0 HER2+ tumors. A clear DFS benefit of ATBC was observed in HR- tumors and/or in presence of lymphovascular invasion.
GW26-e0781 Hyperhomocysteinemia is an independent predictor of long-term clinical outcomes in Chinese octogenarians with acute coronary syndrome
Authors: Zhenhong Fu, Hao Xue, Qiao Xue, Jun Guo, Wei Dong, Mingzhi Shen, Xia Yang, Lian Chen, Yundai Chen
Journal: Journal of the American College of Cardiology (2015)
The Transcription Factor IRF4 Is Crucial for CLL Progression and Regulates Survival and Proliferation in a Microenvironment Related Manner
Authors: Daniela Asslaber, Josefina Pinon Hofbauer, Nadja Zaborsky, Sabine Flenady, Tanja Nicole Hartmann, Richard Greil, Alexander Egle
Journal: Blood (2014)
Impact of Constitutional Polymorphisms in VCAM1, CD44, CXCL12, CXCR4 and CSF3R in Progenitor Cell Mobilization in Patients with Hematological Malignancies
Authors: Maria L. Lozano, Cristina Castilla-Llorente, Elkin A. Niño, Ana I. Antón, Jose Padilla, Encarna Pérez, Vicente Garcia
Journal: Blood (2011)
Safety and Efficacy of Laparoscopic Splenectomy in Patients with Refractory Immune Thrombocytopenic Purpura. A Long-Term Survey
Authors: Nicola Cascavilla, Matteo Scaramuzzi, Michele Nobile, Matteo Dell’Olio, Antonietta Pia Falcone, Lorella Melillo, Grazia Sanpaolo, Potito Rosario Scalzulli, Giovanni Rossi, Antonio La Sala, Carlo Bodenizza, Giovanni D’Arena, Francesco Saverio Mantuano, Michele Mario Greco, Angelo Michele Carella, Emanuela Merla, Angelo Ambrosio, Pierluigi Di Sebastiano
Journal: Blood (2008)
Phase II Study of Combination of the HyperCVAD Regimen with Dasatinib in Patients with Philadelphia Chromosome (Ph) or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL) and Lymphoid Blast Phase Chronic Myeloid Leukemia (CML-LB).
Authors: Farhad Ravandi, Deborah Thomas, Hagop Kantarjian, Stefan Faderl, Charles Koller, Devri Brown, Rebecca Garris, Gautam Borthakur, Jan Burger, Partow Kebriaei, Jeffrey Jorgensen, Dan Jones, Jorge Cortes, Susan O’Brien
Journal: Blood (2007)
Stem cell markers in gastrointestinal cancer
Authors: M. Valladares-Ayerbes, S. Díaz Prado, V. Medina, P. Iglesias, B. Rodríguez, M. Haz, M. Reboredo, M. Quindós, G. Alonso-Jaudenes, L. Antón Aparicio
Journal: Journal of Clinical Oncology (2007)

21095 Background: Cancer cells with stem cells (CSC) properties have been identified in different tumors. It is suggested that CSC are responsible for the continuous growth of tumors, metastasis and drug-resistance. Markers for stem cells have been described. Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells. ABCG2 transporter (MDR1) gene expression has been described as surrogate for the side-population phenotype. PTTG1 has also been recently identified as a component of the molecular signature of human (hu) ES cell-lines. Methods: Using Digital Northern we have demonstrated a significant tag counts for PTTG1 and reticulocalbin 2 (RCN2) in 11 huES cell-lines of the CGAP. The objective of our work has been to assess gene expression of these SC markers in a panel of new gastrointestinal cancer (GC) cells lines (CL) developed in our laboratory. Quantitative assessment was obtained by real-time PCR relative to normal bone marrow (BM), colonic mucosa and established cell-lines. GCCLs have been developed from ascitic fluid obtained of pancreatic carcinoma (MBQ-OJC1) and colon cancer (JJPF-OJC4, LCM-OJC5 and JAC-OJC6). GCCLs had been fully characterized by cytomorphology, epithelial and tumor markers (keratins, EGFR, EpCAM, p53), karyotype and tumor spheroids cultures. Results: Expression for ABCG2, Nanog, Oct4, PTTG1 and RCN2 were clearly detected in all the GCCL. Relative levels for each mRNA shown wide variety. For example, ABCG2 mRNA was highly expressed (2–26 fold) in colon cancer CL relative to BM. RCN2 was overexpressed (more than 2 x 10 2 fold) in 3 GCCL. Conclusions: Our results show that expressions of different “stemness” genes are maintained in cultured cancer cells. These data suggest that CSC are present in metastatic sites and can be maintained in continuous culture. We hypothesized that PTTG1 and RCN2 could be tested as a new cancer stem cells markers. No significant financial relationships to disclose.
Dual Roles for Regulatory T-cell Depletion and Costimulatory Signaling in Agonistic GITR Targeting for Tumor Immunotherapy
Authors: Ashley E. Mahne, Smita Mauze, Barbara Joyce-Shaikh, Jane Xia, Edward P. Bowman, Amy M. Beebe, Daniel J. Cua, Renu Jain
Journal: Cancer Research (2016)

Abstract Agonistic monoclonal antibodies (mAb) targeting the T-cell receptor coregulatory molecule GITR exert potent therapeutic activities in preclinical tumor models. Although anti-GITR mAb are thought to act by depleting and destabilizing the intratumoral T regulatory cell (Treg) population, the precise mechanism of action is obscure. Here, we addressed this issue using a Treg fate-mapping approach, which revealed that Treg loss was primarily due to cell depletion, with minimal evidence of Treg conversion to a non–Foxp3-expressing population. Further characterization of persisting Tregs following anti-GITR mAb treatment showed that a highly activated subpopulation of CD44hiICOShi intratumoral Tregs were preferentially targeted for elimination, with the remaining Tregs exhibiting a less suppressive phenotype. With these changes in the Treg population, intratumoral CD8+ T cells acquired a more functional phenotype characterized by downregulation of the exhaustion markers PD-1 and LAG-3. This reversal of CD8+ T-cell exhaustion was dependent on both agonistic GITR signaling and Treg depletion, as neither mechanism by itself could fully rescue the exhaustion phenotype. Tests of anti-human GITR antibody MK-4166 in a humanized mouse model of cancer mimicked many of the effects of anti-mouse GITR mAb in syngeneic tumor models, decreasing both Treg numbers and immune suppressor phenotype while enhancing effector responsiveness. Overall, our results show how anti-GITR mAb shifts Treg populations to enable immune attack on tumors, with clinical implications for molecular markers to modify emerging treatments. Cancer Res; 77(5); 1108–18. ©2016 AACR.
State-Level Cancer Mortality Attributable to Cigarette Smoking in the United States
Authors: Joannie Lortet-Tieulent, Ann Goding Sauer, Rebecca L. Siegel, Kimberly D. Miller, Farhad Islami, Stacey A. Fedewa, Eric J. Jacobs, Ahmedin Jemal
Journal: JAMA Internal Medicine (2016)

State-specific information about the health burden of smoking is valuable because state-level initiatives are at the forefront of tobacco control. Smoking-attributable cancer mortality estimates are currently available nationally and by cancer, but not by state.To calculate the proportion of cancer deaths among adults 35 years and older that were attributable to cigarette smoking in 2014 in each state and the District of Columbia.The population-attributable fraction (PAF) of cancer deaths due to cigarette smoking was computed using relative risks for 12 smoking-related cancers (acute myeloid leukemia and cancers of the oral cavity and pharynx; esophagus; stomach; colorectum; liver; pancreas; larynx; trachea, lung, and bronchus; cervix uteri; kidney and renal pelvis; and urinary bladder) from large US prospective studies and state-specific smoking prevalence data from the Behavioral Risk Factor Surveillance System.The PAF of cancer deaths due to cigarette smoking in each US state and the District of Columbia.We estimate that at least 167 133 cancer deaths in the United States in 2014 (28.6% of all cancer deaths; 95% CI, 28.2%-28.8%) were attributable to cigarette smoking. Among men, the proportion of cancer deaths attributable to smoking ranged from a low of 21.8% in Utah (95% CI, 19.9%-23.5%) to a high of 39.5% in Arkansas (95% CI, 36.9%-41.7%), but was at least 30% in every state except Utah. Among women, the proportion ranged from 11.1% in Utah (95% CI, 9.6%-12.3%) to 29.0% in Kentucky (95% CI, 27.2%-30.7%) and was at least 20% in all states except Utah, California, and Hawaii. Nine of the top 10 ranked states for men and 6 of the top 10 ranked states for women were located in the South. In men, smoking explained nearly 40% of cancer deaths in the top 5 ranked states (Arkansas, Louisiana, Tennessee, West Virginia, and Kentucky). In women, smoking explained more than 26% of all cancer deaths in the top 5 ranked states, which included 3 Southern states (Kentucky, Arkansas, and Tennessee), and 2 Western states (Alaska and Nevada).The proportion of cancer deaths attributable to cigarette smoking varies substantially across states and is highest in the South, where up to 40% of cancer deaths in men are caused by smoking. Increasing tobacco control funding, implementing innovative new strategies, and strengthening tobacco control policies and programs, federally and in all states and localities, might further increase smoking cessation, decrease initiation, and reduce the future burden of morbidity and mortality associated with smoking-related cancers.
Genetic models for estimating age-specific risk of sporadic breast cancer
Authors: E. R. Jupe, D. A. Ralph, C. E. Aston, S. Manjeshwar, T. D. Pugh, B. A. Gramling, D. C. Defreese, C. D. Shimasaki
Journal: Journal of Clinical Oncology (2006)

10038 Introduction: Accurately assessing individual risk of developing breast cancer is essential for early detection and prevention. The possibility exists to improve upon the widely used Gail model in predicting an individual’s risk of developing breast cancer, by incorporating both genetic and lifestyle information. Methods: We have developed a model with data from ∼7,000 Caucasian women (2,300 cases and 4,700 controls) enrolled in four geographically distinct regions of the US. Questionnaire-based information on clinical and lifestyle variables, including the Gail model questions, were collected. All samples were genotyped for 120 common, functional polymorphisms in candidate genes likely to influence breast carcinogenesis. The data were randomly divided into training (75%) and validation (25%) sets. Because of age-dependent genetic penetrance observed in the study, separate models were built for three age intervals (30–44, 45–54 and ≥ 55). Following assessment of Hardy-Weinberg equilibrium and linkage-disequilibrium, univariate and multivariate statistical analyses were performed to assess genetic main effects and epistatic interactions and define model terms. Models were evaluated by Receiver Operator Curve (ROC) analysis. Results: The riskprediction models developed for all three age intervals were informative with Area Under the Curve (AUC) that was consistently greater than expected by chance and exceeded the predictive power of the Gail model alone. No strong associations were found between scores derived from our models and the Gail model. The results suggest that the genetic markers examined contribute to breast cancer prediction independent of the Gail scores, and due to the improvement in the AUC, probably complement the Gail scores. The strongest genetic contributors to risk were identified in the youngest group where the AUC was 0.71 in the training set and 0.66 in the validation set. Estimated AUC values appear to be quite stable across 1,000 bootstrap samples of training and validation sets. Conclusions: The predictive power of these models integrating both genetic and epidemiological data provides an improved estimate of an individual’s breast cancer risk. [Table: see text]
Adipose-Derived Mesenchymal Stem Cells with Potential to Ameliorate Platelet Recovery and Enhance Megakaryopoiesis in a Mouse Model of Radiation-Induced Thrombocytopenia Via the PI3k/Akt Pathway
Authors: Xiao-Hui Zhang, Jia-Min Zhang, Fei-Er Feng, Qian-Ming Wang, Xiao-Lu Zhu, Shi-Yuan Zhou, Yi Zhou, Hui-Sheng Ai, Xiao Jun Huang
Journal: Blood (2014)
India launches plan for national cancer screening programme
Authors: Sanjeet Bagcchi
Journal: BMJ (2016)

The Indian government has published an operational framework for the country’s first national cancer screening programme, scheduled to start in November 2016.1 There will be mandatory screening for oral, breast, and cervical cancer in people over the age of 30 in 100 districts of India before the programme expands to other areas.

The Indian health minister, Jagat Prakash Nadda, said in a statement, “I am happy that my ministry has developed an operational framework for the screening and management of common cancer . . . This framework provides mechanisms to ‘operationalise’ screening and management of common cancer at field …
High-Performance Computing in Neuroscience for Data-Driven Discovery, Integration, and Dissemination
Authors: Kristofer E. Bouchard, James B. Aimone, Miyoung Chun, Thomas Dean, Michael Denker, Markus Diesmann, David D. Donofrio, Loren M. Frank, Narayanan Kasthuri, Chirstof Koch, Oliver Ruebel, Horst D. Simon, Friedrich T. Sommer, None Prabhat
Journal: Neuron (2016)
White Flag
Authors: Kirstin Hirni, Brian Carter
Journal: Annals of Internal Medicine (2015)

On Being a Doctor17 March 2015White FlagKirstin Hirni, MD and Brian Carter, MDKirstin Hirni, MDFrom University of Missouri-Kansas City and Children's Mercy Hospital, Kansas City, Missouri.Search for more papers by this author and Brian Carter, MDFrom University of Missouri-Kansas City and Children's Mercy Hospital, Kansas City, Missouri.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-2119 Audio Reading - “White Flag” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "White Flag," by K. Hirni and B. Carter. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I gripped the steering wheel with trembling hands as I drove through a light drizzle to the hospital, wondering the whole way, “Is this it?”Grandma was still independent and spunky at the age of 96. She even ran a “bookstore” that amounted to a veritable community and counseling center. Her door was always open to anyone who needed her or just wanted company. Having retired after decades teaching at the local school district, she remained a prominent figure in the community.It was February of my intern year when Grandma came down with a viral illness. Over the course ... Author, Article, and Disclosure InformationAffiliations: From University of Missouri-Kansas City and Children's Mercy Hospital, Kansas City, Missouri.Corresponding Author: Kirstin Hirni, MD, University of Missouri-Kansas City, 2301 Holmes Street, Kansas City, MO 64108; e-mail, [email protected]edu.Current Author Addresses: Dr. Hirni: University of Missouri–Kansas City, 2301 Holmes Street, Kansas City, MO 64108.Dr. Carter: Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108. PreviousarticleNextarticle Advertisement Audio Reading - “White Flag” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "White Flag," by K. Hirni and B. Carter. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 17 March 2015Volume 162, Issue 6Page: 453-454KeywordsBloodBrainChemotherapyHeartLymphomaNeurosurgeryPalliative carePharynxRibsVeins ePublished: 17 March 2015 Issue Published: 17 March 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Phase I, pharmacokinetic (PK), &amp; pharmacodynamic (PD) study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, (17DMAG, NSC 707545) in patients with advanced solid tumors
Authors: M. J. Egorin, C. P. Belani, S. C. Remick, C. Erlichman, C. J. Teneyck, J. L. Holleran, S. P. Ivy, S. Ramalingam, C. L. Naret, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2006)

3021 Background: 17DMAG is a water-soluble analog of 17-allylamino-17-demethoxygeldanamycin (17AAG), the first geldanamycin compound to enter clinical trials. 17DMAG causes oncoprotein degradation by binding to heat shock protein 90 (HSP90) &amp; has greater in-vitro activity than 17AAG. In animals treated with 17DMAG, liver toxicity is dose-limiting. The objectives of this first-in-human study are to: establish the dose-limiting toxicity (DLT); recommend a phase 2 dose; &amp; characterize the PK &amp; PD of 17DMAG. Methods: Using a modified accelerated schema, escalating doses of 17DMAG are given IV over 1 h daily x 5 (schedule A) or daily x 3 (schedule B) every 3 weeks. Plasma 17DMAG concentrations during cycle 1 are quantitated by LC/MS. HSP70 &amp; ILK levels in peripheral mononuclear cells are measured by western blot at baseline &amp; 24 h on d 1. Results: 37 pts have been enrolled. On schedule A, dose levels are 1.5, 3, 6, 9, 12 &amp; 16 mg/m 2 /d (n = 20). On schedule B, the starting dose was 2.5 mg/m 2 /d. Based on safety information from schedule A, subsequent schedule B dose levels were 14, 19, 25 &amp; 34 mg/m 2 /d (n = 17). One DLT was noted in schedule A (16 mg/m 2 ) &amp; consisted of reversible liver enzyme elevation. End-of-infusion (EOI) 17DMAG concentrations (33–2074 ng/ml) &amp; AUC 0–24 (200–5200 ng/ml x h) increase linearly with dose. Interpatient PK variability was substantial, with CV% of 16–59%. The daily administration schedule precluded precise definition of 17DMAG t 1/2 &amp; clearance, but estimates of t 1/2 &amp; clearance ranged from 10.8 to 77 h &amp; 19–160 ml/min/m 2 , respectively. Between 0 &amp; 24 h, 20.5 ± 8.6% (range 4–43.8%) of the administered dose was excreted in urine. HSP70 increased between 0.2 &amp; 3.7 fold above baseline in PBMCs at 24 h at 12, 16, &amp; 25 mg/m 2 . There is an indication of ILK degradation in 3 of 4 patients evaluated at 25 mg/m 2 . Conclusions: 17DMAG is well tolerated at current dose levels &amp; maximal tolerated dose has not been reached. 17DMAG plasma PK are linear over the doses delivered to date, &amp; there is evidence of a target effect as manifested by↑HSP70 &amp; ↓ILK. Support: U01CA099168–01, U01CA62502, U01CA69912, R01CA90390 &amp; NIH/NCCR/GCRC grants #5M01 RR 00056 &amp; M01 RR00080 No significant financial relationships to disclose.