tbuckley/cabot-search huggingface dataset:
Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies
Authors: Timothy M. Shaver, Brian D. Lehmann, J. Scott Beeler, Chung-I Li, Zhu Li, Hailing Jin, Thomas P. Stricker, Yu Shyr, Jennifer A. Pietenpol
Journal: Cancer Research (2016)

Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. Cancer Res; 76(16); 4850-60. ©2016 AACR.
Nonalcoholic fatty liver disease
Authors: Elizabeth M. Brunt, Vincent W.-S. Wong, Valerio Nobili, Christopher P. Day, Silvia Sookoian, Jacquelyn J. Maher, Elisabetta Bugianesi, Claude B. Sirlin, Brent A. Neuschwander-Tetri, Mary E. Rinella
Journal: Nature Reviews Disease Primers (2015)
Effect of Dietary Protein on Morphologic Development of Rat Mammary Gland&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M C Alvarez Sanz, J M Liu, H H Huang, E J Hawrylewicz
Journal: JNCI Journal of the National Cancer Institute (1986)

Isocaloric diets, containing 8% casein [low protein (LP)]. 19.5% casein [normal protein (NP)], or 31% casein [high protein (HP)] and 10% corn oil, were fed to adult virgin female Sprague-Dawley rats prior to conception and were continued through mating, gestation, and lactation. Female pups, 8 per litter, were fed on their mother's diet for the duration of the study. The pups' sexual maturation occurred at 33, 35, and 70 days of age for the HP, NP, and LP groups, respectively. At 7 weeks of age, duct development in the mammary gland was markedly delayed in the LP group. No significant differences in the extent of ductal development were noted between the HP and NP groups. Morphologic development into terminal end buds, alveolar buds, lobules, and terminal ducts was determined for each diet group at 7 weeks and at sexual maturity plus 3 weeks (SM+3) of age. At 7 weeks, the terminal end bud was the dominant structure in the LP group and was significantly greater in number than in the HP and NP groups. The latter groups were dominated by the alveolar bud structures. At SM+3, the number of terminal end buds decreased, and the alveolar buds increased in the LP group; however, the numbers were still significantly different than in the HP and NP groups. This study indicates that dietary protein affects mammary duct proliferation and morphologic development.
Cervical Carcinoma Antigens in the Diagnosis of Human Squamous Cell Carcinoma of the Cervix&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: H G Haines, J P McCoy, D E Hofheinz, A B Ng, S R Nordqvist, R C Leif
Journal: JNCI Journal of the National Cancer Institute (1981)

The use of tumor-associated antigens (TAA) in the diagnosis of human squamous cell carcinoma of the cervix was evaluated by immunofluorescence staining of second cervical scrapes and touch preparations of normal and carcinomatous tissue. Rabbit antisera, prepared against human cervical squamous cell carcinoma homogenates and absorbed with normal human cervix and plasma, were used to stain 103 second cervical scrapes by indirect immunofluorescence. Of these specimens, 59 were positive by immunofluorescence, whereas the remaining 44 were negative. Compared with conventional cytologic diagnosis, positive immunofluorescence was detected in 100% (49/49) of the second scrapes from patients with cervical dysplasia or carcinoma (for a false-negative rate of zero). Of the second cervical scrapes from 57 patients negative by cytology, 13 were positive by immunofluorescence (for a false-positive rate of 22.8%). Indirect immunofluorescence tests on tumor touch preparations also revealed cervical TAA in other types of gynecologic tumors.
SAKK 65/08: A Phase I Dose Escalation Study of Bortezomib in Combination with Nelfinavir in Patients with Advanced Hematologic Malignancies
Authors: Christoph Driessen, Jürgen Bader, Marianne Kraus, Markus Jörger, Hilde Rosing, Gregoire Berthod, Felicitas Hitz, Catherine Berset, Alexandros Xyrafas, Hanne Hawle, Hermann S Overkleeft, Christiana Sessa, Alwin Huitema, Ulrich JM Mey, Thomas Pabst, Roger von Moos, Dagmar Hess
Journal: Blood (2014)
Validity of Determining Circumcision Status by Questionnaire as Related to Epidemiological Studies of Cancer of the Cervix&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Abraham M. Lilienfeld, M.D., M.P.H., Saxon Graham, Ph,D.
Journal: JNCI Journal of the National Cancer Institute (1958)

Comparison of patients' statements with examination findings concerning circumcision of a series of 213 male patients admitted to the Roswell Park Memorial Institute indicated disagreement between examination and statement in 34.4 percent of the patients. Persons whose statements agreed and disagreed with examination were similar in birthplace, languages read and spoken, socioeconomic category of occupation, and age. Analysis of the proportion of disagreeing patients examined by each physician indicated general similarity. Characteristics of patients who stated they were not circumcised, when the physician determined they were circumcised, were not significantly different from those who reported circumcision when the examiner recorded the reverse. However, the first-mentioned group was consistently different to a slight extent from the other in characteristics suggesting less familiarity with the English language. Also, there was a smaller proportion of professional workers in this group, and they were somewhat older. Further study regarding the relationship of circumcision to cervical cancer should be based on physical-examination findings with adequate definitions of degree of length of prepuce.
Evaluating Markers for Guiding Treatment
Authors: Stuart G Baker, Marco Bonetti
Journal: JNCI Journal of the National Cancer Institute (2016)

The subpopulation treatment effect pattern plot (STEPP) is an appealing method for assessing the clinical impact of a predictive marker on patient outcomes and identifying a promising subgroup for further study. However, its original formulation lacked a decision analytic justification and applied only to a single marker.We derive a decision-analytic result that motivates STEPP. We discuss the incorporation of multiple predictive markers into STEPP using risk difference, cadit, and responders-only benefit functions.Applying STEPP to data from a breast cancer treatment trial with multiple markers, we found that none of the three benefit functions identified a promising subgroup for further study. Applying STEPP to hypothetical data from a trial with 100 markers, we found that all three benefit functions identified promising subgroups as evidenced by the large statistically significant treatment effect in these subgroups.Because the method has desirable decision-analytic properties and yields an informative plot, it is worth applying to randomized trials on the chance there is a large treatment effect in a subgroup determined by the predictive markers.
Troubled Times
Authors: John Lister
Journal: New England Journal of Medicine (1974)

AT a recent meeting when the intractable problem of finding means of reconciling the training requirements of young doctors with the service requirements of the hospitals was once more being discussed, a senior medical officer from the Department of Health remarked that he was sad to see the medical profession in such disarray. There was certainly some justification in the remark because there is no doubt that the tensions between the different sections of the profession have recently become more acute. In particular the consultants and specialists, especially those working in district general hospitals, have been giving signs of serious . . .
Routine Aspirin or Nonsteroidal Anti-inflammatory Drugs for the Primary Prevention of Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement
Journal: Annals of Internal Medicine (2007)

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendation and supporting scientific evidence on routine use of aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer. The complete information on which this statement is based, including evidence tables and references, is available in the accompanying articles in this issue and on the USPSTF Web site (http://www.preventiveservices.ahrq.gov). The USPSTF is redesigning its recommendation statement in response to feedback from primary care clinicians. The USPSTF plans to release, later in 2007, a new, updated recommendation statement that is easier to read and incorporates advances in USPSTF methodology. The recommendation statement below is an interim version that combines existing language and elements with a new format. Although the definitions of grades remain the same, other elements have been revised.
Abstract PR06: Precision medicine for newly diagnosed and refractory/recurrent pediatric cancer patients: Lessons learned from “N=1” studies
Authors: Troy A. McEachron, Keri B. Zabokrtsky, Aaron F. Sassoon, Sara Nasser, Tyler Izatt, Chad P. Garner, David W. Craig, John D. Carpten, Leonard S. Sender
Journal: Clinical Cancer Research (2016)

Abstract Whole genome sequencing has rapidly emerged as the preferred method for unbiased genomic interrogation. Leveraging this technology, we have developed a precision medicine clinical research protocol for pediatric, adolescent, and young adult cancer patients. The primary objective of this study is to arrive at genome informed treatment recommendations for individual patients suffering from aggressive and/or worsening disease in a clinically relevant time frame. The second objective is to survey the genomic landscape of newly diagnosed and recurrent/refractory patients. To accomplish this, we have employed an interdisciplinary workflow including a customized bioinformatic analysis pipeline, contextual biological interpretation of the data, and case reviews during weekly molecular tumor board meetings. Here we report the results of having sequenced over 50 patients diagnosed with both common and rare malignancies. Factors affecting the successful identification of therapeutically actionable targets and subsequent intervention are varied. The most consistent findings are the increased mutation burden in patients who have received chemotherapy and/or radiation prior to tissue collection. Lastly, we highlight the realistic opportunities, challenges, and insight gained from an ongoing single institution experience. This abstract is also presented as Poster 27. Citation Format: Troy A. McEachron, Keri B. Zabokrtsky, Aaron F. Sassoon, Sara Nasser, Tyler Izatt, Chad P. Garner, David W. Craig, John D. Carpten, Leonard S. Sender. Precision medicine for newly diagnosed and refractory/recurrent pediatric cancer patients: Lessons learned from “N=1” studies. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr PR06.
The impact of political process on hospital psychiatry
Authors: G L Hogben, T Critelli, R Hoffman
Journal: American Journal of Psychiatry (1979)

Political forces motivated the New York State Department of Health to withhold payment for Medicaid-financed inpatients on therapeutic passes. The elimination of therapeutic passes had many negative effects on patient care. The authors believe this experience demonstrates that political factors can overwhelm standard clinical practice and reasoned health planning to force irrational change on health care delivery.
Reply:
Authors: Naoki Tanaka, Frank J. Gonzalez
Journal: Hepatology (2012)

We thank Drs. Gabbi and Gustafsson for their interest in our study on serum metabolomic analysis of nonalcoholic steatohepatitis (NASH) in mice.1 We measured the hepatic contents of taurocholate and tauro-β-muricholate using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry. However, the hepatic levels of these bile acids were not decreased in mice treated for 2 weeks with a methionine- and choline-deficient (MCD) diet (Fig. 1). Although changes in expression of the canalicular bile acid transporters were not detected, hepatic bile excretion might be decreased to some degree. When hepatic bile acid levels are altered, the expression of small heterodimer partner (Shp) may be changed accordingly to maintain hepatic bile acid levels. Indeed, the levels of Shp mRNA were decreased by MCD treatment, even in the absence of a significant decrease in hepatic bile acid content (Fig. 2). These findings suggest an abnormal response of transcription factors and their target genes associated with bile acid homeostasis, and thus we propose a disruption of bile acid homeostasis during the course of NASH where proinflammatory cytokines and cellular stress may disrupt bile acid homeostasis, causing a vicious cycle. Thus, we are generally in agreement with Drs. Gabbi and Gustafsson's view that clarification of the dynamic changes in bile acid homeostasis and the related transcriptional factors during NASH development might lead to new bile-modulating therapies for NASH. Hepatic levels of taurocholate and tauro-β-muricholate in mice treated for 2 weeks with methionine- and choline-supplemented control diet (MCS), choline-deficient diet (CD), methionine- and choline-deficient diet (MCD), and methionine-deficient diet (MD). The levels of bile acids were normalized to those of MCS-treated mice and were expressed as relative abundance. Values were expressed as mean ± standard deviation (n = 5 in each group), and statistical analyses were performed using the 1-way analysis of variance with Tukey's test. Time course of small heterodimer partner mRNA levels during treatment with methionine- and choline-supplemented control diet (MCS) and methionine- and choline-deficient diet (MCD) diets. The mRNA levels were normalized to those of 18S ribosomal mRNA and subsequently normalized to those of mice after a 3-day MCS diet treatment. The values were expressed as mean ± standard deviation (n = 5 in each group), and statistical analysis was performed using the 2-tailed Student t test in the same treatment period. Naoki Tanaka M.D., Ph.D*, Frank J. Gonzalez Ph.D.*, * Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Nicotine potentiation of haloperidol in reducing tic frequency in Tourette's disorder [published erratum appears in Am J Psychiatry 1991 Sep;148(9):1282]
Authors: B J McConville, M H Fogelson, A B Norman, W M Klykylo, P Z Manderscheid, K W Parker, P R Sanberg
Journal: American Journal of Psychiatry (1991)

In an open, nonblind study, 10 patients with Tourette's disorder who were being treated with haloperidol were videotaped before, while, and after chewing nicotine gum. The frequency of tics was reduced significantly during the 30-minute gum-chewing period and during the 1 hour after gum chewing. Nicotine appears to potentiate haloperidol effects in patients with Tourette's disorder.
School-Level Practices to Increase Availability of Fruits, Vegetables, and Whole Grains, and Reduce Sodium in School Meals — United States, 2000, 2006, and 2014
Authors: Caitlin Merlo, Nancy Brener, Laura Kann, Tim McManus, Diane Harris, Kristy Mugavero
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Students consume up to half of their daily calories at school, often through the federal school meal programs (e.g., National School Lunch Program) administered by the U.S. Department of Agriculture (USDA). In 2012, USDA published new required nutrition standards for school meals.* These standards were the first major revision to the school meal programs in >15 years and reflect current national dietary guidance and Institute of Medicine recommendations to meet students' nutrition needs. The standards require serving more fruits, vegetables, and whole grains and gradually reducing sodium content over 10 years. To examine the prevalence of school-level practices related to implementation of the nutrition standards, CDC analyzed data from the 2000, 2006, and 2014 School Health Policies and Practices Study (SHPPS) on school nutrition services practices related to fruits, vegetables, whole grains, and sodium. Almost all schools offered whole grain foods each day for breakfast and lunch, and most offered two or more vegetables and two or more fruits each day for lunch. The percentage of schools implementing practices to increase availability of fruits and vegetables and decrease sodium content in school meals increased from 2000-2014. However, opportunities exist to increase the percentage of schools nationwide implementing these practices.
Impact of age, ECOG PS and type of treatment on progression-free survival and overall survival in second-line therapy for advanced gastric cancer: analysis on 709 cases
Authors: V. Fanotto, C. Fontanella, M. Uccello, G. Pasquini, S. Bozzarelli, F. Leone, M. Russano, G. Rosati, G. Tomasello, N. Silvestris, F. Pietrantonio, I. Paladina, E.S. Lutrino, D. Melisi, L. Antonuzzo, C. Caparello, S. Cordio, V. Rotella, L. Rimassa, G. Aprile
Journal: Annals of Oncology (2015)
Safety and Efficacy of Neoadjuvant Folfirinox in Patients (Pts) with Locally Advanced Pancreatic Adenocarcinoma (Lapc)
Authors: M.M. Khushman, N. Scherfenberg, P. Hosein, M. Velez, L. Carcas Peirce, D. Dammrich, J. Hurtado-Cordovi, R. Parajuli, T. Pollack, A.P. Harwood, J. Macintyre, J. Merchan, A. Loaiza-Bonilla, I.I. Akunyili, M. Restrepo, G. Narayanan, L. Portelance, D. Sleeman, J. Levi, C. Rocha-Lima
Journal: Annals of Oncology (2014)
In Vitro Culture of Cells Isolated From Dimethylnitrosamine-Induced Renal Mesenchymal Tumors of the Rat. I. Qualitative Morphology 2
Authors: Gordon C. Hard, R. Borland
Journal: JNCI Journal of the National Cancer Institute (1975)

The in vitro morphology of cells isolated from renal mesenchymal tumors induced in rats by a single ip injection of dimethylnitrosamine was followed in short- and long-term culture. The morphology of cells isolated from normal rat-kidney cortex was studied for comparison. Primary tumor-cell isolates consisted of a range of mesenchymal cell forms interspersed between discrete, homogeneous islands of cohesive epithelium-like cells. The latter were presumably derived from renal parenchyma that had been engulfed within the in vivo neoplasm by proliferating tumor cells, since this epithelial component did not survive serial subculture. Established tumor cell lines consisted of a pleomorphic range of mesenchymal forms resembling the descriptions of various cell types in vitro, including fibroblasts, smooth muscle cells, and endothelial cells. A range of mesenchymal cell forms in culture therefore correlated with the heterogeneous histologic nature of the in vivo neoplasm in which fibroblasts, smooth muscle fibers, and endothelium-like cells were also represented. Multinucleate or polymorphonuclear giant cells were characteristic of tumor cell cultures, whereas large, expanded polygonal cells with longitudinal striations were characteristic of normal kidney cell cultures. Some tumor cell cultures were typified by cells with cytoplasmic vacuolation and some by the acquisition of an epithelioid form at high cell density, a change not preceded by islands of cohesive, epithelium-like cells at preconfluent stages.
Abstract 3336: Early Management and Norepinephrine Withdrawal But Not Hormonal Therapy, Improve Donor Heart Function
Authors: Rajamiyer V Venkateswaran, Richard P Steeds, Ian C Wilson, Jorge G Mascaro, Richard D Thompson, Jonathan N Townend, Robert S Bonser
Journal: Circulation (2006)

Objectives: To assess the role of early management, tri-iodothyronine (T3) and methylprednisolone (MP) therapy in potential heart donors. Methods: In a prospective randomized double blind trial, 80...
Abstract A20: Innovative drug discovery for bladder cancer by miR-130 family seed-targeting locked nucleic acid
Authors: Hiroshi Egawa, Kentaro Jingushi, Yuko Ueda, Kaori Kitae, Wataru Nakata, Kazutoshi Fujita, Motohide Uemura, Norio Nonomura, Kazutake Tsujikawa
Journal: Cancer Research (2016)

Abstract Bladder cancer causes an estimated 150,000 deaths per year worldwide. Although 15% of the recurrent bladder cancer becomes an invasive type, targeted therapy for malignant bladder cancer does not make much progress. To investigate a novel therapeutic target, we focused on miRNA expression signatures obtained from bladder cancer clinical specimens, and found that the miR-130 family (miR-130b, miR-301a and miR-301b) was significantly up-regulated in bladder cancer specimens compared to adjacent normal urothelial specimens. Functional analyses revealed that the miR-130 family promoted bladder cancer cell migration and invasion by regulating both focal adhesion kinase (FAK) and Akt phosphorylation. Moreover, miR-130b directly targeted Phosphatase and Tensin Homolog Deleted from Chromosome 10 (PTEN), which suppresses FAK and Akt activation. Furthermore, Argonaute2-immunoprecipitation and the subsequent gene array analysis identified tyrosine-protein phosphatase non-receptor type 11 (PTPN11) as another target gene of both miR-130b and miR-301b. Thus, the miR-130 family promotes bladder cancer cell motility by regulating these target genes. We next designed miR-130 family-targeted LNA (Locked Nucleic Acid) that can inhibit entire miR-130 family through a common seed sequence. miR-130 family-targeted LNA suppressed bladder cancer cell proliferation, migration and invasion powerfully by targeting both PTEN and PTPN11. Furthermore, miR-130 family-targeted LNA significantly inhibits bladder tumor growth in a murine xenograft model. Taken together, the miR-130 family has a crucial role for malignant progression of bladder cancer and thus miR-130 family-targeted LNA could be a promising molecular-targeted drug for bladder cancer. Citation Format: Hiroshi Egawa, Kentaro Jingushi, Yuko Ueda, Kaori Kitae, Wataru Nakata, Kazutoshi Fujita, Motohide Uemura, Norio Nonomura, Kazutake Tsujikawa. Innovative drug discovery for bladder cancer by miR-130 family seed-targeting locked nucleic acid. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A20.