tbuckley/cabot-search huggingface dataset:
Abstract IA03: The evolutionary landscape of CLL: Therapeutic implications
Authors: Catherine J. Wu
Journal: Clinical Cancer Research (2016)

Abstract Clonal evolution is a key feature of cancer progression and relapse. Recent studies across cancers have demonstrated the extensive degree of intratumoral heterogeneity present within individual cancers. We hypothesized that evolutionary dynamics contribute to the variations in disease tempo and response to therapy that are highly characteristic of chronic lymphocytic leukemia (CLL). We have recently investigated this phenomenon by developing a pipeline that estimates the fraction of cancer cells harboring each somatic mutation within a tumor through integration of whole-exome sequence (WES) and local copy number data (Landau et al., Cell 2013). By applying this analysis approach to 149 CLL cases, we discovered earlier and later cancer drivers, uncovered patterns of clonal evolution in CLL and linked the presence of subclones harboring driver mutations with adverse clinical outcome. Thus, our study, generated from a heterogeneous sample cohort, strongly supports the concept that CLL clonal evolution arises from mass extinction and therapeutic bottlenecks which lead to the emergence of highly fit (and treatment resistant) subclones. We further hypothesized that epigenetic heterogeneity also shapes CLL clonal evolution through interrelation with genetic heterogeneity. Indeed, in recent work, we have uncovered stochastic methylation disorder as the primary cause of methylation changes in CLL and cancer in general, and that this phenomena impacts gene transcription, genetic evolution and clinical outcome. Thus, integrated studies of genetic and epigenetic heterogeneity in CLL have revealed the complex and diverse evolutionary trajectories of these cancer cells. Immunotherapy is exquisitely suited for specifically and simultaneously targeting multiple lesions. We have developed an approach that leverages whole-exome sequencing to systematically identify personal tumor mutations with immunogenic potential, which can be incorporated as antigen targets in multi-epitope personalized therapeutic vaccines. We are pioneering this approach in an ongoing trial in melanoma and will now expand this concept to address diverse malignancies. Our expectation is that the choice of tumor neoantigens for a vaccine bypasses thymic tolerance and thus generates highly specific and potent high-affinity T cell responses to eliminate tumors in any cancer, including both trunk and branch lesions. Citation Format: Catherine J. Wu. The evolutionary landscape of CLL: Therapeutic implications. [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 IA03.
A MYC–aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer
Authors: Daniel Dauch, Ramona Rudalska, Giacomo Cossa, Jean-Charles Nault, Tae-Won Kang, Torsten Wuestefeld, Anja Hohmeyer, Sandrine Imbeaud, Tetyana Yevsa, Lisa Hoenicke, Tatu Pantsar, Przemyslaw Bozko, Nisar P Malek, Thomas Longerich, Stefan Laufer, Antti Poso, Jessica Zucman-Rossi, Martin Eilers, Lars Zender
Journal: Nature Medicine (2016)
Strand and Cell Type-specific Function of microRNA-126 in Angiogenesis
Authors: Qinbo Zhou, Chastain Anderson, Jakub Hanus, Fangkun Zhao, Jing Ma, Akihiko Yoshimura, Shusheng Wang
Journal: Molecular Therapy (2016)

microRNAs or miRs have been shown to be pivotal modulators of vascular development. The strand and cell type-specific function of miR-126 in angiogenesis, especially pathological angiogenesis, remains poorly defined. We characterized the retinal vascular phenotype of miR-126-/- mice, and tested the function of miR-126 strands (miR-126-3p and -5p) using in vitro angiogenesis models and a mouse model of neovascular age-related macular degeneration. We found that miR-126 is critical for retinal vascular development but has dual function in pathological angiogenesis. miR-126-/- mice showed defective postnatal retinal vascular development and remodeling, which is partially rescued by genetic knockout of its target gene Spred-1. Surprisingly, either silencing miR-126-3p by LNA-antimiR or overexpressing miR-126-3p by miRNA mimic repressed laser-induced choroidal neovascularization. To dissect the underlying mechanism, we found in endothelial cells, silencing of miR-126-3p repressed angiogenesis, while overexpression of miR-126-5p enhanced angiogenesis. However, in retinal pigment epithelial cells, miR-126-3p repressed vascular endothelial growth factor (VEGF-A) expression via a novel mechanism of regulating αB-Crystallin promoter activity and by directly targeting VEGF-A 3'-untranslated region. These findings provide first genetic evidence that miR-126 is required for the development of different retinal vascular layers, and also uncover a strand and cell type-specific function of miR-126 in ocular pathological angiogenesis.
Tai chi improves pain in patients with knee arthritis, trial finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Tai chi produced beneficial effects similar to a standard course of physical therapy in the treatment of knee osteoarthritis, a randomised single blind trial has shown.1

Tai chi is a traditional Chinese practice that combines meditation with slow, gentle movements, deep breathing, and relaxation. It has previously been shown to alleviate symptoms of knee osteoarthritis, but no trials directly compared tai chi with standard care.

The new …
The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype
Authors: Matthew J. Schultz, Andrew T. Holdbrooks, Asmi Chakraborty, William E. Grizzle, Charles N. Landen, Donald J. Buchsbaum, Michael G. Conner, Rebecca C. Arend, Karina J. Yoon, Christopher A. Klug, Daniel C. Bullard, Robert A. Kesterson, Patsy G. Oliver, Amber K. O'Connor, Bradley K. Yoder, Susan L. Bellis
Journal: Cancer Research (2016)

Abstract The glycosyltransferase ST6Gal-I, which adds α2-6–linked sialic acids to substrate glycoproteins, has been implicated in carcinogenesis; however, the nature of its pathogenic role remains poorly understood. Here we show that ST6Gal-I is upregulated in ovarian and pancreatic carcinomas, enriched in metastatic tumors, and associated with reduced patient survival. Notably, ST6Gal-I upregulation in cancer cells conferred hallmark cancer stem-like cell (CSC) characteristics. Modulating ST6Gal-I expression in pancreatic and ovarian cancer cells directly altered CSC spheroid growth, and clonal variants with high ST6Gal-I activity preferentially survived in CSC culture. Primary ovarian cancer cells from patient ascites or solid tumors sorted for α2-6 sialylation grew as spheroids, while cells lacking α2-6 sialylation remained as single cells and lost viability. ST6Gal-I also promoted resistance to gemcitabine and enabled the formation of stably resistant colonies. Gemcitabine treatment of patient-derived xenograft tumors enriched for ST6Gal-I–expressing cells relative to pair-matched untreated tumors. ST6Gal-I also augmented tumor-initiating potential. In limiting dilution assays, subcutaneous tumor formation was inhibited by ST6Gal-I knockdown, whereas in a chemically induced tumor initiation model, mice with conditional ST6Gal-I overexpression exhibited enhanced tumorigenesis. Finally, we found that ST6Gal-I induced expression of the key tumor-promoting transcription factors, Sox9 and Slug. Collectively, this work highlighted a previously unrecognized role for a specific glycosyltransferase in driving a CSC state. Cancer Res; 76(13); 3978–88. ©2016 AACR.
Ivabradine
Authors: Mitchell A. Psotka, John R. Teerlink
Journal: Circulation (2016)

Ivabradine is approved to reduce hospitalizations for patients with symptomatic heart failure, reduced ejection fraction, and persistently elevated heart rate despite otherwise maximal medical therapy. However, the eligible patient population is a small fraction of those with heart failure overall. This review summarizes the major clinical evidence supporting the use of ivabradine, identifies and discusses areas of uncertainty from the clinical trial data, helps describe the population most likely to benefit, and attempts to place ivabradine within the multifaceted treatment scheme currently used for patients with heart failure and reduced ejection fraction.
Somatization and psychiatric disorder in the NIMH Epidemiologic Catchment Area study
Authors: G E Simon, M VonKorff
Journal: American Journal of Psychiatry (1991)

Somatization has often been viewed as a defense against awareness of emotional distress or as a masked version of depression. This report examines whether community residents with high levels of functional somatic symptoms also report overt psychological distress and whether somatization is associated with any specific psychiatric disorder.Analyses used data from the community sample of the National Institute of Mental Health Epidemiologic Catchment Area (ECA) study, a population-based survey of psychiatric morbidity among more than 18,000 residents of five U.S. communities.Increasing number of somatization symptoms was strongly associated with overt expression of psychological distress and psychiatric symptoms. Among ECA respondents with five or more current functional somatic symptoms, 63% reported current psychological symptoms and 50% met criteria for a current psychiatric diagnosis (compared to 7% and 6%, respectively, among those with no current somatization symptoms). Somatization symptoms showed strongest associations with anxiety and depressive symptoms, intermediate association with symptoms of psychotic disorders, and weakest associations with symptoms of substance abuse and antisocial personality.ECA study respondents with high levels of somatization symptoms typically reported overt psychological distress, especially anxiety and depression. Patterns of response do not support a dissociation between physical and emotional symptoms. Functional somatic symptoms appear to be common expressions of distress instead of defenses against awareness.
The perils of motherhood at age 14
Authors: Rebecca Coombes
Journal: BMJ (2016)

Keya, aged 14, is pictured with her 2 month old son, Rahim, at home in an urban slum in Bangladesh. Keya, who lives with her 21 year old husband and his parents, almost lost her life as a result of a postpartum haemorrhage.

“When I got married at 13 I was happy,” …
Rubella vaccination: persistence of antibodies for up to 16 years.
Authors: S O'Shea, J M Best, J E Banatvala, W C Marshall, J A Dudgeon
Journal: BMJ (1982)

Sera from 123 volunteers vaccinated six to 16 years previously with one of four rubella vaccines (Cendehill, RA27/3, HPV77-DE5, and To-336) were tested for rubella antibodies by single radial haemolysis and radioimmunoassay. By radioimmunoassay 110 (89.4%) of the vaccinees had antibody concentrations greater than the minimum immune titre (that is, greater than 15,000 IU/1), 11 (8.9%) were seropositive but had concentrations less than or equal to 15,000 IU/1, and two (1.6%) were seronegative. Eight (6.5%) were seronegative by single radial haemolysis, of whom five had received Cendehill vaccine. Six to eight years after vaccination subjects who had received Cendehill vaccine had the lowest geometric mean titre of antibody by radioimmunoassay while the subjects who had received HPV77-DE5 vaccine had the highest. Although antibody concentrations less than or equal to 15,000 IU/1 were not detected among subjects given RA27/3 vaccine six to eight years previously, such low levels were detected in two (15.4%) vaccinated 11-16 years previously. These results emphasise the importance of long-term surveillance programmes so that vaccination policies may be reviewed.
Detection of LA and LAA Thrombus by CMR in Patients Referred for Pulmonary Vein Isolation
Authors: Danai Kitkungvan, Faisal Nabi, Mohamad G. Ghosn, Amish S. Dave, Miguel Quinones, William A. Zoghbi, Miguel Valderrabano, Dipan J. Shah
Journal: JACC. Cardiovascular imaging (2016)

The goal of this study was to evaluate the diagnostic performance of a comprehensive, multicomponent cardiac magnetic resonance (CMR) study for assessment of left atrial (LA) and left atrial appendage (LAA) thrombus.Pre-operative evaluation for pulmonary vein isolation (PVI) typically requires tomographic imaging to define pulmonary venous anatomy and transesophageal echocardiogram (TEE) to assess for the presence of LA/LAA thrombus. CMR is increasingly being used to define pulmonary venous anatomy before PVI. Limited data are available on the utility of a multicomponent CMR protocol in assessing LA/LAA thrombus.We studied patients who underwent multicomponent CMR for evaluation of pulmonary venous anatomy before PVI and underwent TEE within 7 days. LA and LAA thrombi were evaluated by using CMR as follows: 1) cine-CMR; 2) contrast-enhanced magnetic resonance angiography; and 3) equilibrium phase delayed enhancement (DE) CMR with a long inversion time (TI) of 600 ms (long TI DE-CMR). Components of the CMR study were evaluated for diagnostic performance for detection of LA or LAA thrombus using TEE as the reference standard.During the study period, 261 patients were assessed. The median CHA2DS2VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score was 2, and 73.6% of patients were undergoing anticoagulation therapy. CMR and TEE were performed within 1.3 ± 2.3 days. LA/LAA thrombi were discovered in 9 patients (3.5%) by using TEE. Among the CMR techniques performed, long TI DE-CMR had the highest diagnostic accuracy (99.2%), sensitivity (100%), and specificity (99.2%), followed by contrast-enhanced magnetic resonance angiography (accuracy 94.3%; sensitivity 66.7%; and specificity 95.2%) and cine-CMR (accuracy 91.6%; sensitivity 66.7%; and specificity 92.5%).In patients referred for PVI, CMR could be a single complete diagnostic study for assessment of pulmonary venous anatomy as well as presence of LA/LAA thrombi, thus reducing the number of pre-operative tests before PVI. Long TI DE-CMR has the best diagnostic performance and should be used for the detection of LA/LAA thrombi.
L’échoendoscopie de contraste harmonique avec analyse de la courbe temps-intensité pour les tumeurs intra-canalaires papillaires et mucineuses du pancréas
Authors: M. Palazzo
Journal: Endoscopy (2015)

Les tumeurs intra-canalaires papillaires et mucineuses du pancréas (TIPMP) incluent un large spectre de lésions avec un grade histologique allant de la dysplasie légère au carcinome invasif. La prédiction préopératoire de ce grade est difficile. L’échoendoscopie de contraste harmonique permet une étude de la microvascularisation dans une pathologie au cours de laquelle on sait que la néo-angiogenèse est une étape-clef de la carcinogénèse. Le but de cette étude était d’évaluer la précision diagnostique de l’échoendoscopie de contraste harmonique avec analyse de la courbe temps-intensité pour le diagnostic différentiel entre une TIPMP avec dysplasie légère/modérée et une TIPMP avec dysplasie de haut grade ou carcinome invasif.
The Preventability of Cancer
Authors: Graham A. Colditz, Siobhan Sutcliffe
Journal: JAMA Oncology (2016)

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 Oncology 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 Oncology journal
EMOTIONS AND BODILY CHANGES
Journal: Annals of Internal Medicine (1935)

This fourth edition of Dr. Dunbar's book is a monumental work which should be considered a classic in the field of psychosomatic medicine. Here in one volume is compiled a systematic survey of psychosomatic interrelationships. The book is outstanding as a reference work in that in addition to 751 pages of abstracted material there are 263 pages of bibliography. The first part of the book consists of orientation and methodology, under which are discussed such subjects as "Problems of Integration and Differentiation," "Acute and Chronic Illness," and "Problems of Measurement." Part 2 of the book is related to the great organ systems, so that one may review contributions pertinent to gastroenterology, cardiovascular medicine, endocrinology, etc. In a volume of this size it is most difficult for a reviewer to cover the work in detail. Not being a psychiatrist, it would be presumptuous for this reviewer to attempt any specific criticism
The role of plasma amine oxidase, platelet monoamine oxidase, and red cell catechol-O-methyl transferase in severe behavioral reactions to disulfiram
Authors: L F Major, D L Murphy, E S Gershon, G L Brown
Journal: American Journal of Psychiatry (1979)

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.
The relative-rate test of the molecular clock hypothesis: a note of caution.
Authors: S Scherer
Journal: Molecular Biology and Evolution (1989)

An important role in the controversy has been assigned to the relative-rate test of molecular evolution (Sarich and Wilson 1973), since it can be applied without referring to geological time (for review, see Wilson et al. 1977).This test has been used widely as ultima ratio in order to support the rateconstancy hypothesis of molecular evolution (for recent examples, see, e.g., Bledsoe 1987; Easteal 1988), although it was pointed out more than 10 years ago that the relative-rate test cannot detect changes in the evolutionary rate if proteins change their rates proportionally (Fitch 1976).In the present letter, the potential failure of the relative-rate test to support the rate-constancy hypothesis is emphasized using Cu-Zn superoxide dismutase ( SOD), since this protein has been considered to be a very poor evolutionary clock (for a detailed discussion of nine sequences, see Lee et al. 1985;
Posttraumatic stress disorder, hypnotizability, and imagery
Authors: R K Stutman, E L Bliss
Journal: American Journal of Psychiatry (1985)

Twenty-six Vietnam veterans were studied to determine the relationship between posttraumatic stress disorder and hypnotizability. The intensity of their posttraumatic stress disorder was measured by a self-report. Their hypnotizability scores, vividness of imagery scores, and symptomatic profiles were also ascertained. Veterans with low or no posttraumatic stress disorder scores had normal hypnotizability scores and normal imagery scores, whereas those with high posttraumatic stress disorder scores had high hypnotizability scores and high imagery scores. The authors conclude that either combat traumas enhanced hypnotic potential in some veterans or that veterans with excellent hypnotic potential to begin with were more susceptible to posttraumatic stress.
Validity of subtyping psychotic depression: examination of phenomenology and demographic characteristics
Authors: N Breslau, H Y Meltzer
Journal: American Journal of Psychiatry (1988)

The authors examine the validity of subtyping psychotic depression by comparing 111 patients with schizoaffective, unipolar, and bipolar psychotic depression on demographic characteristics and symptoms at index episode. Diagnoses were made by using Research Diagnostic Criteria (RDC). The three groups were indistinguishable in sex, race, and age at onset. Schizoaffective patients had more "schizophrenic" symptoms but were not different in depressive delusions, other psychotic symptoms, or affective symptoms. However, bipolar patients scored significantly higher than nonbipolar patients on hypomania. There is little support in these data for the schizoaffective versus nonschizoaffective distinction. Further tests are needed, including tests of response to treatment and biological markers.
Chromatographic Separation of Some Metabolites of the Carcinogen &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide
Authors: John H. Weisburger, Elizabeth K. Weisburger, Harold P. Morris, Herbert A. Sober
Journal: JNCI Journal of the National Cancer Institute (1956)

Journal Article Chromatographic Separation of Some Metabolites of the Carcinogen N-2-Fluorenylacetamide Get access John H. Weisburger, John H. Weisburger Laboratory of Biochemistry, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth K. Weisburger, Elizabeth K. Weisburger Laboratory of Biochemistry, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold P. Morris, Harold P. Morris Laboratory of Biochemistry, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert A. Sober Herbert A. Sober Laboratory of Biochemistry, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 17, Issue 3, September 1956, Pages 363–374, https://doi.org/10.1093/jnci/17.3.363 Published: 01 September 1956 Article history Received: 21 May 1956 Published: 01 September 1956