tbuckley/cabot-search huggingface dataset:
Abstract 2225: Comprehensive molecular characterization of esophageal squamous cell carcinoma
Authors: Dechen Lin, Xuan Meng, Liang Xu, Lingwen Ding, Manoj Garg, Henry Yang, Lizhen Liu, Jiajie Hao, Mingrong Wang, Yasunobu Nagata, Yusuke Sato, Yusuke Okuno, Seishi Ogawa, Phillip Koeffler
Journal: Cancer Research (2014)

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a world-wide prevalent cancer, which is particularly common in certain regions of Asia. However, the genetic alterations of this disease have not been fully described. Methods We determined the mutational landscape of ESCC through whole-exome or targeted deep sequencing of 139 tumor/germline pairs. The somatic copy number variations (SCNV) of over 180 ESCC tumors were analyzed by SNP-array or array-CGH. Candidate driver mutations were mathematically calculated by the most updated algorithm MutSigCV, and the protein expression of which were thoroughly evaluated by immunohistochemistry. Finally, biological effects of candidate drivers were examined through functional studies in vitro and in vivo. Results Deep sequencing and computational analysis identified frequent and novel driver mutations affecting genes such as FAT1 (11.5%), ZNF750 (7.2%), EP300 (7.9%) and MLL2 (18.0%). FAT1 and ZNF750 genes were homozygouly deleted in 3.5% and 3.4% ESCCs, respectively, and their RNA transcripts and proteins were expressed at much lower levels in primary tumors compared to adjacent normal esophageal epithelial. Importantly, silencing of wild-type FAT1 or ZNF750 expression with siRNA/shRNAs significantly promoted cell proliferation and decreased cell differentiation, whereas ectopic expression of these genes resulted in opposite biological consequences. These genetic alterations and biological evidence strongly suggest that FAT1 and ZNF750 likely encode tumor suppressors which are frequently disrupted in ESCC. Furthermore, by integrating the landscape of somatic mutation, SCNV and protein dysregulation, we proposed that RTK-PI3K-MAPK pathways, cell cycle and epigenetic regulation are frequently altered by multiple molecular mechanisms in esophageal tumors. Finally, our systematic approaches uncovered many novel druggable candidates in this disease, such as FGFR1, ALK and XPO1. Conclusions By demonstrating the genomic landscape of over 180 ESCC cases, our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets. Citation Format: Dechen Lin, Xuan Meng, Liang Xu, Lingwen Ding, Manoj Garg, Henry Yang, Lizhen Liu, Jiajie Hao, Mingrong Wang, Yasunobu Nagata, Yusuke Sato, Yusuke Okuno, Seishi Ogawa, Phillip Koeffler. Comprehensive molecular characterization of esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2225. doi:10.1158/1538-7445.AM2014-2225
Science, medicine, and the future: Genetics and cardiovascular risk
Authors: I. N M Day, D. I Wilson
Journal: BMJ (2001)

Cardiovascular disease is the commonest cause of death in the Western world, and congenital heart disease affects almost 1% of liveborn infants. Both diseases have substantial genetic components. The identification of specific genetic variations that underpin cardiovascular disease is providing new opportunities for diagnostic testing, pharmacogenetics, and drug development. In this review we describe genes that are known to have an important impact on the development of cardiovascular disease and discuss how their identification may improve risk management.

This review is based on our research and clinical experience in human genetics, pathology, and medicine. Citations for the topics discussed derive from literature searches in PubMed, OMIM (Online McKusick Inheritance in Man), and online US and European patent databases (USPTO and Esp@cenet respectively).

Variations in the genes for low density lipoprotein receptor, apolipoprotein B, and apolipoprotein E have a considerable effect on individuals' plasma cholesterol concentrations (fig 1).



Fig 1. 
Effects of genetic variation on population distribution of plasma cholesterol concentration. Polymorphisms in the apolipoprotein E gene (APOE) cause an average 10% lowering (E2 allele) or raising (E4 allele) of cholesterol concentration compared with homozygosity for E3. A single defective allele of the apolipoprotein B gene (APOB) has a heterogeneous effect on cholesterol. A defect in the low density lipoprotein receptor gene (LDLR) leads to a rough doubling in cholesterol concentration for heterozygotes and greater increases for homozygotes



### Variations in the low density lipoprotein receptor gene

Familial hypercholesterolaemia is known to be caused by codominant mutations in the low density lipoprotein (LDL) receptor gene.1 Affected individuals typically have cholesterol concentrations twice the population average for their age and sex. This disorder often results in heart attacks in middle age in the 1 in 500 heterozygotes in populations exposed to a Western diet and in childhood coronary disease in the 1 in a million homozygotes in all populations. The disorder …
Prenatal diagnosis of genetic skin disease by fetoscopy and electron microscopy: report on 5 years' experience
Authors: R.A.J. Eady, D.B. Gunner, M.J. Tidman, A.H.M. Heagerty, K.H. Nicolaides, C.H. Rodeck
Journal: British Journal of Dermatology (1985)

Journal Article Prenatal diagnosis of genetic skin disease by fetoscopy and electron microscopy: report on 5 years' experience Get access R.A.J. Eady, R.A.J. Eady Department of Electron Microscopy and Cell Pathology, Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar D.B. Gunner, D.B. Gunner Department of Electron Microscopy and Cell Pathology, Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar M.J. Tidman, M.J. Tidman Department of Electron Microscopy and Cell Pathology, Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar A.H.M. Heagerty, A.H.M. Heagerty Department of Electron Microscopy and Cell Pathology, Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar K.H. Nicolaides, K.H. Nicolaides Harris‐Birthright Research Centre for Fetal Medicine, King's College Medical School, London Search for other works by this author on: Oxford Academic Google Scholar C.H. Rodeck C.H. Rodeck Harris‐Birthright Research Centre for Fetal Medicine, King's College Medical School, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Page 45, https://doi.org/10.1111/j.1365-2133.1985.tb13015.x Published: 01 July 1985
Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease
Authors: Shiqi Yang, Ayman Koteish, Huizhi Lin, Jiawen Huang, Tania Roskams, Valina Dawson, Anna Mae Diehl
Journal: Hepatology (2004)

Hepatic steatosis may have a generally benign prognosis, either because most hepatocytes are not significantly injured or mechanisms to replace damaged hepatocytes are induced. To determine the relative importance of these mechanisms, we compared hepatocyte damage and replication in ethanol-fed and ob/ob mice with very indolent fatty liver disease to that of healthy control mice and PARP-1(-/-) mice with targeted disruption of the DNA repair enzyme, poly(ADP-ribose) polymerase. Compared to the healthy controls, both groups with fatty livers had significantly higher serum alanine aminotransferase values, hepatic mitochondrial H(2)O(2) production, and hepatocyte oxidative DNA damage. A significantly smaller proportion of the hepatocytes from fatty livers entered S phase when cultured with mitogens. Moreover, this replicative senescence was not reversed by treating cultured hepatocytes with agents (i.e., betaine or leptin) that improve liver disease in intact ethanol-fed or leptin-deficient mice. Hepatocytes from PARP1(-/-) mice also had more DNA damage and reduced DNA synthesis in response to mitogens. However, neither mice with fatty livers nor PARP-1-deficient mice had atrophic livers. All of the mice with senescent mature hepatocytes exhibited hepatic accumulation of liver progenitor (oval) cells and oval cell numbers increased with the demand for hepatocyte replacement. Therefore, although hepatic oxidant production and damage are generally increased in fatty livers, expansion of hepatic progenitor cell populations helps to compensate for the increased turnover of damaged mature hepatocytes. In conclusion, these results demonstrate that induction of mechanisms to replace damaged hepatocytes is important for limiting the progression of fatty liver disease.
Variant angina pectoris. Role of coronary spasm in the development of fixed coronary obstructions.
Authors: J C Kaski, D Tousoulis, E McFadden, F Crea, W I Pereira, A Maseri
Journal: Circulation (1992)

It has been suggested that recurring coronary artery spasm may lead to the development of fixed atherosclerotic coronary obstructions.We studied 10 patients with typical Prinzmetal's variant angina in whom the disease remained active for years and in whom occlusive coronary spasm occurred reproducibly at the same arterial site during repeat coronary arteriography (25 +/- 12 months after initial angiography). At initial evaluation, four patients had significant (greater than or equal to 50% fixed coronary diameter reduction) one-vessel coronary artery disease, and six had nonsignificant disease. Spasm developed at stenotic sites (20-65% diameter reduction) in nine patients and at an angiographically normal site in one patient. Progression of coronary disease was assessed in 62 segments: 10 spastic (of which nine were stenotic) and 52 nonspastic (eight stenotic and 44 angiographically normal), using computerized arteriography. Mean diameters (millimeters) of spastic segments, nonspastic stenoses, and angiographically normal nonspastic segments were not significantly different at first and second arteriograms (1.52 +/- 0.14 versus 1.43 +/- 0.21, 1.32 +/- 0.17 versus 1.12 +/- 0.23, and 2.40 +/- 0.12 versus 2.42 +/- 0.12, respectively). Stenosis progression (from 65% diameter reduction to total occlusion) occurred in one patient at a spastic site and in two at nonspastic sites (from 34% to 65% and from 84% to 100%). Complicated stenoses suggestive of plaque fissuring were not observed during the study.In patients with chronic Prinzmetal's variant angina without myocardial infarction, stenosis progression was not frequently observed at spastic sites despite the recurrence of focal coronary spasm over relatively long periods of time.
Immunologic Distinction between Infectious and Serum Hepatitis
Authors: A. M. Prince, R. L. Hargrove, W. Szmuness, C. E. Cherubin, V. J. Fontana, G. H. Jeffries
Journal: New England Journal of Medicine (1970)

Serums from patients with acute viral hepatitis were tested for the presence of the serum-hepatitis (SH) antigen to determine whether this would permit distinction between the two major types of viral hepatitis. None of four patients with short-incubation MS-1 infection (Willowbrook) had detectable antigen, whereas this antigen was identified in all eight cases of long-incubation MS-2 infection (Willowbrook). Correspondingly, only one out of 74 cases associated with four epidemics of infectious hepatitis, and none of 19 sporadic cases occurring in children under the age of 14 showed presence of detectable antigen, whereas 76 of 116 cases (66 per cent) that followed exposure to contaminated needles and 25 of 43 post-transfusion cases (58 per cent) were positive. SH antigen was also detected in 71 of 129 patients (55 per cent) with viral hepatitis who gave no history of parenteral exposure. Serum-hepatitis virus thus appears to be the major cause of sporadic hepatitis in urban adults regardless of the presence or absence of parenteral exposure to blood or blood products.
Calcific Constrictive Pericarditis: Is It Still with Us?
Authors: Lieng H. Ling, Jae K. Oh, Jerome F. Breen, Hartzell V. Schaff, Gordon K. Danielson, Douglas W. Mahoney, James B. Seward, A. Jamil Tajik
Journal: Annals of Internal Medicine (2000)

Background: The presence of pericardial calcification on a plain radiograph strongly suggests constrictive pericarditis in patients with heart failure. However, calcific constrictive pericarditis is considered rare in the United States since tuberculosis incidence has decreased, and doubt has therefore been raised about the importance of this radiologic finding in modern cardiovascular practice. Objective: To determine the clinical and prognostic significance of pericardial calcification on radiography in patients with constrictive pericarditis. Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: A consecutive series of 135 patients (mean age ± SD, 56 ± 16 years) who from 1985 through 1995 had constrictive pericarditis confirmed surgically (n = 133) or by autopsy (n = 2). Patients were divided into two groups: those with pericardial calcification on chest radiography (group I) and those without (group II). Measurements: Clinical and diagnostic findings were compared in both groups, and outcome was compared in 132 patients who had pericardiectomy. Results: Pericardial calcification was seen in 36 patients (27%). The cause of constrictive pericardial disease was indeterminate in 67% of patients in group I and in 21% of patients in group II (P < 0.001). Patients in group I had had symptoms for a longer period and were more likely to have pericardial knock, larger atrial size, and atrial arrhythmia. Significantly more perioperative deaths were seen in group I, but incidence of late survival and incidence of noncalcific disease were similar in both groups. Conclusions: Pericardial calcification is a common finding in patients with constrictive pericarditis. It is often associated with idiopathic disease and other markers of disease chronicity and is an independent predictor of increased perioperative mortality rates.
US healthcare kickback schemes come under heavy scrutiny
Authors: O. Dyer
Journal: BMJ (2015)

Two Florida doctors have agreed to settle allegations that they accepted kickbacks disguised as salaries for their wives in return for referrals to a home healthcare company

Alan Buhler and Craig Prokos, physicians, and their wives Lynn Buhler and Cynthia Prokos, are the sixth and seventh couples to settle accusations of violating the False Claims Act in cases brought against the company A Plus Home Health Care. The Buhlers will pay $1.05m (£0.7m; €0.95m) and the Prokos couple $90 000. In addition to the salaries paid to the two physicians’ wives, who allegedly performed few of the duties for which they were supposedly being paid, Alan Buhler also accepted and tried to conceal payments made to him as a medical director, the government …
Abstract 3550: Curcumin suppresses growth of human mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis
Authors: Ying Wang, Arun K. Rishi, Wenjuan Wu, Lisa Polin, Sunita Sharma, Edi Levi, Steven Albelda, Harvey I. Pass, Anil Wali
Journal: Cancer Research (2011)

Abstract Malignant Pleural Mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis regulatory pathways are frequently altered in MPM and thus remain attractive targets for therapeutic intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. Here we investigated the biological and molecular responses of MPM cells to Curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of Curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose and time dependent manner while pretreatment of MPM cells with Curcumin enhanced Cisplatin efficacy. Curcumin activated stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, Curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of Curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, Curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in development of effective therapeutic treatment options against resistant MPM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3550. doi:10.1158/1538-7445.AM2011-3550
Abstract 2476: Synthesis of novel aza-podophyllotoxins derivatives substituted at ring-A and their activities on NCI-60 human tumor cell line.
Authors: Ajay Kumar, Vineet Kumar, Sanjay V. Malhotra, Alegria E. Antonio
Journal: Cancer Research (2013)

Abstract Podophyllotoxin is a major cytotoxic constituent of several members of Podophyllum peltatum species. The semisynthetic derivatives namely etoposide, etopophos and teniposide have been developed from podophyllotoxin and are currently used in clinic for the treatment of several human tumors since five decades. Synthesis of podophyllotoxin is not feasible so far and due to this reason structural modification of podophyllotoxin could not be explored very well. The structural complexity of podophyllotoxin, arising from the presence of four stereogenic carbons in ring C has restricted most of the structural activity relationship (SAR) studied by derivatization of the parent natural product rather than by de novo multi-step chemical synthesis. In past we have developed various heterocyclic analogues of podophyllotoxin derivatives. Owing to their promising activity against 60 cell lines at NCI, we are actively engaged in developing new library of N-hydroxyethyl-4-aza-didehyropodophyllotoxin derivatives. A new library of aza-podophyllotoxin derivatives substituted at ring-A has been developed and followed by a screen of in vivo activity using a panel of tumor hollow-grafts implanted in mice consisting of breast (MDA-MB-231), non-small lung (NCI-H23 and NCI-H522), colon (SW-620 and COLO 205), melanoma (UACC-62, MDA-MB-435 and LOXIMVI), ovarian (OVCAR-5 and OVCAR-3) and CNS (U251 and SF-295) cell lines. These new compounds found to have comparatively good activity against colon and cancer lines. Citation Format: Ajay Kumar, Vineet Kumar, Sanjay V. Malhotra, Alegria E. Antonio. Synthesis of novel aza-podophyllotoxins derivatives substituted at ring-A and their activities on NCI-60 human tumor cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2476. doi:10.1158/1538-7445.AM2013-2476 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
The John Phillips Memorial Lecture: Changing Patterns of Susceptibility of Some Common Bacterial Pathogens to Antimicrobial Agents.
Authors: Maxwell Finland
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971The John Phillips Memorial Lecture: Changing Patterns of Susceptibility of Some Common Bacterial Pathogens to Antimicrobial Agents.Maxwell Finland, M.D., M.A.C.P.Maxwell Finland, M.D., M.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-843_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptStudies on the in vitro susceptibility to all antibiotics available and in general use at the time have been carried out periodically with contemporary strains of some of the commoner bacterial pathogens isolated at the Boston City Hospital. Some of the results of these studies are reviewed and correlated with certain properties of the bacteria and with some features of the patients from whom they were isolated. In particular, the effect of the intensive use of antibiotics on the resistance of selected species and on the changing ecology of serious bacterial infections within the hospital are analyzed and discussed.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 843-843KeywordsAntibioticsAntimicrobialsBacteriaBacterial pathogensEcology Issue Published: 1 May 1971 PDF downloadLoading ...
The Family Medical History: Assessing Patient Understanding of Diabetes Mellitus
Authors: Rachelle S Doody, Nellie P Grose
Journal: Diabetes Care (1981)

In this preliminary study, we attempted to determine whether diabetic subjects with a positive family medical history for diabetes have a better understanding of their own disease (ie., of its course, treatment, and genetic characteristics) than diabetic subjects without diabetes in their histories. We interviewed 50 diabetic subjects and scored their responses to determine their understanding of diabetes in general and in their own cases in particular. The data were analyzed using the Student's t test and chi-square analysis. Overall, patients with positive histories did not have significantly higher understanding than patients with negative histories. However, if patients had extensive exposure to the affected relative, or if tht relative was a spouse or a parent, the patients' understanding was significantly higher (P &amp;lt; 0.05). Educational level, age, and duration of diabetes did not affect patients' understanding. The data suggest that the family medical history can be a valuable teaching model, once we redefine it so as to reconcile patient concepts about illness with physician concepts of disease.
The Tobacco Buyout and the FDA
Authors: Steven A. Schroeder
Journal: New England Journal of Medicine (2004)

An unlikely alliance between tobacco growers and tobacco-control advocates will be tested this fall, as a congressional conference committee attempts to reconcile separate versions of tobacco legislation that the House and the Senate have attached to the Foreign Sales Corporation Act. On June 17, 2004, the House voted to abolish a long-standing quota system (whereby a defined number of farmers are permitted to grow tobacco in quantities set by the government each year) and to pay $9.6 billion from the federal treasury to tobacco farmers to ease the transition. In addition, the House bill would eliminate all existing restrictions on . . .