tbuckley/cabot-search huggingface dataset:
Abstract 2392: Hyaluronan-dependent growth of human triple negative breast cancer MDA-MB-468 in mouse xenograft models
Authors: Chunmei Zhao, Mathieu Marella, Susan Zimmerman, Lei Huang, H. Michael Shepard, Zhongdong Huang
Journal: Cancer Research (2015)

Abstract Hyaluronan (also known as hyaluronic acid or HA) is a nonsulfated glycosaminoglycan in the extracellular matrix. Elevated levels of HA in the tumor microenvironment have been associated with poor prognosis of several human cancers, including pancreatic, breast, colon and prostate. In many cases of breast cancer, HA is found to be associated with the stromal compartment. To understand the interaction between tumor cells and HA containing stromal compartment, we engineered a HA-high stromal cell line by overexpressing the human HAS3 gene in Balb/c 3T3 fibroblast cells. In vitro, the 3T3/HAS3 cells produced and secreted HA, which was shown to bind to the HA-low/CD44-high breast cancer cell line MDA-MB-468 at the cell surface. When co-grafted with MDA-MB-468 cells in mice, 3T3/HAS3 cells promoted the in vivo growth of MDA-MB-468 cells. Furthermore, depletion of HA with PEGPH20 (a pegylated form of the recombinant human PH20 protein) significantly inhibited the growth of MDA-MB-468 cells co-grafted with 3T3/HAS3 cells, suggesting that the HA provided by 3T3/HAS3 cells is critical for the growth of MDA-MB-468 cells in vivo. Immunohistochemical analysis of tumor xenograft samples showed that HA-low MDA-MB-468 cells were surrounded by HA-high stromal cells, resembling the tumor morphology observed in certain breast cancer patients. To model for breast cancers with tumor cell-associated HA, we overexpressed the human HAS3 gene directly in MDA-MB-468 cells. The in vivo growth of MDA-MB-468 was significantly enhanced by HAS3 overexpression. Depletion of HA by PEGPH20 synergized with Abraxane and improved its anti-cancer efficacy in the MDA-MB-468/HAS3 xenograft model compared to PEGPH20 and Abraxane alone. Taken together, we have developed tumor xenograft models that mimic HA-high breast cancers and can be used to test the pharmacological activity of anticancer agents. Further characterization of these models will provide insights into the understanding of the mechanisms by which increased levels of HA and the associated changes in the tumor microenvironment promote the disease progression in breast cancer and how depletion of HA can interfere with this process and synergize with chemotherapies to inhibit tumor progression. Citation Format: Chunmei Zhao, Mathieu Marella, Susan Zimmerman, Lei Huang, H. Michael Shepard, Zhongdong Huang. Hyaluronan-dependent growth of human triple negative breast cancer MDA-MB-468 in mouse xenograft models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2392. doi:10.1158/1538-7445.AM2015-2392
Abstract P052: Coronary Heart Disease Mortality Declines in the United States From 1980 through 2011: Evidence for Stagnation in Young Adults, Especially Women
Authors: Kobina A Wilmot, Martin O’Flaherty, Simon Capewell, Earl S Ford, Viola Vaccarino
Journal: Circulation (2015)

Background: Cardiovascular mortality rates have fallen dramatically over the past four decades. However, recent unfavorable trends in coronary heart disease (CHD) risk factors among young adults (obesity, diabetes, and tobacco use) raise concerns about their subsequent impact on CHD mortality. Furthermore, recent data from the US and other countries suggest a worsening of CHD incidence and mortality among young women. We therefore examined recent trends in CHD mortality rates in the US according to age and sex. Methods: We used mortality data between 1980 and 2011 from US adults ≥ 25 years. We calculated age-specific CHD mortality rates and estimated annual percentage change (EAPC) for US adults, and compared three decades of data (1980-1989, 1990-1999, and 2000-2011). We also used Joinpoint regression modeling to assess changes in trends over time, based on inflection points of the mortality distribution. Results: Young men and women (aged&lt;55 years) showed a robust decline in CHD mortality from 1980 until 1989 (EAPC -5.5% in men and -4.6% in women). However, the two subsequent decades saw stagnation with minimal improvement (Table). This was particularly true for young women who had no improvements between 1990 and 1999 (EAPC +0.1%), and only -1% EAPC since 2000. In contrast, older adults (65+years) showed steep annual declines since 2000, approximately doubled compared with the previous period (women, -5.0% and men, -4.4%). Jointpoint analyses provided consistent results. Conclusions: The dramatic declines in cardiovascular mortality since 1980 conceals major heterogeneities. CHD death rates in older groups are now falling steeply. However, young men and women have enjoyed small decreases in CHD mortality rates since 1990. The drivers of these major differences in CHD mortality trends by age and sex needs urgent study.
Severity of airflow obstruction using NHANESIII versus ERS/GLI12 prediction equations in Caucasian American pulmonary laboratory patients
Authors: Olinto Linares-Perdomo, Dave Collingridge, Dean Sorenson, Matthew Matthew, Denitza Blagev, Robert L. Jensen, John Hankinson, Alan Morris
Journal: European Respiratory Journal (2014)

RATIONALE:   Spirometric airway obstruction severity is based on prediction equations. We examined the NHANESIII and ERS/GLI12 prediction equations for categorizing airway obstruction severity.    METHODS:   We used 12,239 clinical spirograms from 10 to 95 year old Caucasian males and females referred to pulmonary laboratories at Intermountain Medical Center and LDS Hospital (Salt Lake City) from 2001 to 2013. Spirograms met reproducibility and acceptability criteria. We used lower predicted limits from NHANESIII (Hankinson et al.,1999) and the ERS-Task Force Global Lung Initiative (ERS/GLI12) (Quanjer PH et al., 2012) equations.   RESULTS:   Of the 12,239 spirograms, 3901 (31.8%) had airway obstruction by NHANESIII and 3937 (32.2%) were obstructed by ERS/GLI12. NHANESIII and GLI/ERS12 equations categorized, respectively, 1428 (11.8%) and 1487 (12.1%) as mild, 647 (5.3%) and 659 (5.4%) as moderate, 616 (5%) and 613 (5%) as moderately severe, 690 (5.6%) and 676 (5.5%) as severe, and 500 (4%) and 502 (4%) as very severe airway obstruction.  Figure: Spirometric categorization of airway obstruction in Caucasian American pulmonary laboratory patients using the NHANES-III and ERS/GLI-12 prediction equations.   CONCLUSION:   NHANESIII and ERS/GLI12 prediction equations categorize airway obstruction in an American Caucasian pulmonary laboratory population in a similar manner.
Impact of teaching and awareness programme on doctors' knowledge of chest drain insertion site
Authors: Mithun Murthy, Joanna Gallagher, Nicola Stevenson
Journal: European Respiratory Journal (2011)

Aim: To assess if doctors identify correct site for chest drain insertion. To assess impact of teaching programme on their knowledge.

Method: In 2008, 111 doctors were asked to identify correct drain insertion site for uncomplicated pneumothorax by marking photographs. Data were collected on grade, specialty and prior experience (Gallagher JL; Stevenson N. Thorax 2009; 64 (Suppl IV):A166). In 2010, 102 doctors surveyed after introduction of teaching programme.

Results: We had 108 responses in '08 compared to 100 in '10. 55/108 (51%) correctly marked site in 2008 compared to 75/100 (75%) in 2010.

View this table:

Incorrect marking by grade; both years





View this table:

Incorrect marking by specialty (2010)





83% doctors with prior respiratory experience were correct in '10 compared with 62% in '08. 75% Associate specialists, 86% Consultants, 100% F2s, 73% SHOs and 95% SpRs who felt confident at performing procedure, correctly identified site. In '10, 68% doctors received formal training.

Conclusions: Correct identification of insertion site improved in all grades after structured teaching and awareness programmes. Doctors with previous respiratory experience or in surgical specialties had better knowledge. Most had reasonable assessment of their competence and majority received training. Formal training should be given to all doctors.
Passive Paw Anaphylaxis in the Rat Optimum
Authors: B. A. Baldo, P. G. Thomas, Catherine L. Nelson, K. M. Taylor
Journal: Allergy (1980)

The difficulties involved in quantitating passive cutaneous anaphylaxis led us to examine the rat paw as a site for passive anaphylaxis and to define optimum conditions for passive paw anaphylaxis. Generation of homocytotropic antibodies in a number of different rat strains revealed that female Brown Norway rats were excellent producers of high titre antisera after only a single injection of antigen and Bordetella pertussis. Injection of ratpaws with diluted antisera followed by short (1-2 h) or long (72 h or more) sensitization periods showed that maximum paw swelling occurred 15 min after antigen challenge. Retention of tissue sensitizing capacity in the paw for greater than 35 days but loss of this capacity following heating of antiserum at 56 degrees C, indicated that the rat homocytotropic antibodies involved in passive paw anaphylaxis belong to the IgE class. Experiments using mepyramine, methysergide and diethylcarbamazine showed that 5-hydroxytryptamine is the most important mediator of passive paw anaphylaxis after both a short (2 h) and a long (72 h) sensitization procedure. Passive paw anaphylaxis in the rat is at least as easy to perform as passive cutaneous anaphylaxis, results can be obtained more rapidly and accurate measurement of paw thickness is not difficult. The procedure is a viable alternative to passive cutaneous anaphylaxis and may offer advantages over the latter method especially in the search for, and rapid assessment of, anti-allergic compounds.
The concept of splitting and its clinical relevance
Authors: Salman Akhtar, Jessica P. Byrne
Journal: American Journal of Psychiatry (1983)

After briefly reviewing various contributions to the concept of splitting, the authors describe the clinical manifestations of this defense. These include 1) inability to experience ambivalence, 2) impaired decision making, 3) oscillation of self-esteem, 4) egosyntonic impulsivity, and 5) intensification of affects. The authors then discuss the relevance of such conceptualizations to the differential diagnosis and psychotherapy of personality disorders.
Profound parental bias associated with chromosome 14 acquired uniparental disomy indicates targeting of an imprinted locus
Authors: A Chase, W Leung, W Tapper, A V Jones, L Knoops, C Rasi, L A Forsberg, P Guglielmelli, K Zoi, V Hall, L Chiecchio, L Eder-Azanza, C Bryant, L Lannfelt, L Docherty, H E White, J Score, D J G Mackay, A M Vannucchi, J P Dumanski, N C P Cross
Journal: Leukemia (2015)

Acquired uniparental disomy (aUPD) is a common finding in myeloid malignancies and typically acts to convert a somatically acquired heterozygous mutation to homozygosity. We sought to identify the target of chromosome 14 aUPD (aUPD14), a recurrent abnormality in myeloid neoplasms and population cohorts of elderly individuals. We identified 29 cases with aUPD14q that defined a minimal affected region (MAR) of 11.2 Mb running from 14q32.12 to the telomere. Exome sequencing (n=7) did not identify recurrently mutated genes, but methylation-specific PCR at the imprinted MEG3-DLK1 locus located within the MAR demonstrated loss of maternal chromosome 14 and gain of paternal chromosome 14 (P<0.0001), with the degree of methylation imbalance correlating with the level of aUPD (r=0.76; P=0.0001). The absence of driver gene mutations in the exomes of three individuals with aUPD14q but no known haematological disorder suggests that aUPD14q may be sufficient to drive clonal haemopoiesis. Analysis of cases with both aUPD14q and JAK2 V617F (n=11) indicated that aUPD14q may be an early event in some cases but a late event in others. We conclude that aUPD14q is a recurrent abnormality that targets an imprinted locus and may promote clonal haemopoiesis either as an initiating event or as a secondary change.
Diagnosis of Hepatic Granulomas: A Review<sup>1</sup>
Authors: P R Mills, R I Russell
Journal: Journal of the Royal Society of Medicine (1983)

Hepatic epithelioid granulomas are relatively common, being found in 3-10% of liver biopsy specimens (Guckian & Perry 1966). Epithelioid granulomas are focal aggregates of modified macrophages, termed epithelioid cells, which are thought to form around poorly soluble antigens, and should be distinguished from lipogranulomas which are found in association with fatty change. The liver is an organ very rich in reticuloendothelial cells which undertake detoxification of numerous substances; therefore the liver is a common site for granuloma detection. Unfortunately, the formation of granulomas is a nonspecific reaction to a large variety of noxious stimuli and only rarely can the pathologist provide further information of diagnostic help. The term 'granulomatous hepatitis' should be avoided as hepatocellular dysfunction is uncommon in association with hepatic granulomas.
Abstract 4060: Androgen receptor is involved in the migration and invasion of triple-negative breast cancer cells
Authors: Qiao-dan ZHENG, Wenyuan Wu, Cai Huang
Journal: Cancer Research (2014)

Abstract Triple-negative breast cancer(TNBC)is a major world health problem, accounting for more than 15% of breast cancer new cases each year. The 5-year survival rate for TNBC is approximately 54.5% and death usually occurs as a result of local invasion and regional metastases. A complete understanding of the molecular mechanisms that control the aggressive behavior of triple-negative breast cancer cells is essential in order to develop targeted therapies to manage the disease. Recent evidence has suggested a role of Androgen receptor (AR)in cellular motility and invasion. In this present study we examined the role of AR on the migration and invasion of triple-negative breast cancer cells. Detect the AR levels in 7 cell line of breast cancer cells including MCF-7, MDA-MB-157, MDA-MB-231, MDA-MB-435, MDA-MB-468, MDA-MB-549, HS-578T by Q-PCR, we demonstrate that AR is highly express in triple-negative breast cancer cells; shRNAs specific to AR have been generated and delivered into human breast cancer cells by lentiviral vectors. We showed that the total levels of AR can be decreased by AR shRNA and inhibit MDA-MB-231 cellular motility and large focal adhesion (FA) formation, the cell migration was determined by time-lapse cell migration assays, depletion of endogenous AR significantly reduced the velocity and directionality of cell migration, and strongly inhibited the net distance of cell migration, indicating that AR modulates cell migration by controlling the velocity and directionality of migration. We also showed that AR activation and the migration and invasion of MDA-MB-231 , MDA-MB-435, MDA-MB-468 can be strongly inhibited with commercially available AR blocker Bicalutamide by cell migration and invasion assay. These results suggest that AR in breast cancer cells is required for cellular migration and invasion. Citation Format: Qiao-dan ZHENG, Wenyuan Wu, Cai Huang. Androgen receptor is involved in the migration and invasion of triple-negative breast cancer cells. [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 4060. doi:10.1158/1538-7445.AM2014-4060
Abstract 3947: BP1 protein, a transcription factor, is secreted by breast cancer cells
Authors: Jinguen Rheey, Anna Yakovleva, Kellie-Ann Yamane, Patricia E. Berg
Journal: Cancer Research (2015)

Abstract Background. BP1 is a homeobox gene which is normally expressed during early hematopoiesis. Homeotic proteins regulate the expression of multiple genes involved in development and differentiation. We have previously shown that BP1 mRNA and protein levels are elevated in 80% of women with invasive ductal breast cancer. Furthermore, BP1 protein (pBP1) overexpression is associated with larger and more aggressive breast tumors. In cultured breast cancer cell lines overexpressing pBP1, we observe decreased cell death and increased proliferation. BP1 overexpression has also been found to stimulate known oncogenes including BCL2 and c-MYC. Methods. Levels of pBP1 were detected in cell extracts (CE) and conditioned media (CM) using Western Blot analysis. Depleted media (DM), in which the pBP1 was removed, and recombinant BP1 protein (rpBP1) were used as controls. Cell viability was assessed using MTT assays. Real-time qPCR was used to measure expression of selected oncogenes. Results. Our results show that: (a) pBP1 is secreted from three breast cancer cell lines but not from two normal breast epithelial cell lines. (b) pBP1 exhibits mitogenic activity towards breast cancer cells and normal breast cells, whether cells are grown in media containing 10x conditioned medium (CM) from cells secreting pBP1 or in media containing purified recombinant pBP1 (rpBP1). (c) Growth of breast cancer cells or normal breast epithelial cells in CM or rpBP1 leads to up-regulation of selected oncogenes known to be targets of BP1. These oncogenes include BCL2 and MET. BP1 itself was stimulated, but only in normal breast epithelial cells. The mechanism of secretion is under investigation. Conclusions. Our data suggest that secreted pBP1 can stimulate cell proliferation and gene expression in tumor cells as well as in nearby normal cells. Citation Format: Jinguen Rheey, Anna Yakovleva, Kellie-Ann Yamane, Patricia E. Berg. BP1 protein, a transcription factor, is secreted by breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3947. doi:10.1158/1538-7445.AM2015-3947
Spontaneous pneumothorax: Epidemiology in France
Authors: Antonio Bobbio, Agnes Dechartres, Samir Bouam, Emelyne Canny, Nicolas Roche, Marco Alifano
Journal: European Respiratory Journal (2014)

Background.  Epidemiology of spontaneous pneumothorax has been scanty studied in recent years in spite of new pathogenic insights.   Aim and objectives.  The aim of the study was to study the characteristics of spontaneous pneumothorax in a nationwide population database.   Methods.  The database of the French National health system of hospital admissions between 2008 and 2011 was explored. Information for each hospital stay included age, sex, primary versus secondary character, type of unit admission, duration of hospital stay, and month of hospitalization.   Results.  A total of 59,658 hospital admissions for patients aged>14 years were retrieved, with an estimated annual incidence of 17/100,000 inhabitants. Sex ratio was 1/3.35 and hospital re-admissions in between two years were estimated at 34%. Mean age of patients was 38 ±19 years. Winter, spring, summer and fall hospitalizations accounted for 25%, 25%, 24% and 26%, respectively (p=0.01). Primary pneumothorax accounted for 85% of hospitalizations. In 24% of cases a surgical procedure was performed. Surgical treatment was correlated with age (p   Conclusions.  Sex and age are important determinants in presentation and management of spontaneous pneumothorax.
Obesity, pain, and sedation are important
Authors: A. Higgs
Journal: BMJ (1996)

EDITOR,—John C Hall and colleagues stratify their patients as high risk only on the basis of American Society of Anesthesia grade (>1) and advanced age (>60 years) and then imply that other putative risk factors are similar in the two (high and low risk) groups. They seem to ignore one major risk factor for the development of postoperative respiratory complication—namely, obesity. Although the two groups are …
Abstract 110: The role of the p53 target Wig-1 in senescence and cancer
Authors: Fredrik Jerhammar, Cinzia Bersani, Dijana Djureinovic, Patrick Micke, Klas G. Wiman
Journal: Cancer Research (2015)

Abstract The wild type p53-induced gene 1, Wig-1 (also known as Zmat3 or PAG608) binds to AU-rich elements in mRNAs and thereby regulates important tumor associated factors including p53, FAS, and N-Myc. Focusing on normal human diploid fibroblasts (HDF), we are now exploring the role of Wig-1 in senescence. SiRNA-mediated Wig-1 depletion increases senescence markers such as Beta-galactosidase staining, H3K9me3, H4K20me3, and p21. Also, Wig-1 is spontaneously downregulated in cells undergoing replicative senescence. The trimethylation of lysine 9 on histone 3 (H3K9me3) is an established marker of cellular senescence and increases upon siRNA-mediated Wig-1 knockdown in HDF cells. It is also increased in late passage (senescent) fibroblasts that express low Wig-1 levels. Our RNA-immunoprecipitation sequencing (RIP-seq) data of tumor cells shows that Wig-1 binds histone-modifying enzymes SUV39H2 (which trimethylates H3K9), and subunits of PP1 (protein phosphatase 1, which dephosphorylates H3T10). These mRNAs have AU-rich elements in the 3´UTR. Importantly, we have observed that both SUV39H2 and its corresponding methylation (H3K9me3) is increased upon Wig-1 silencing. In a cohort of 350 lung cancer patients, we found Wig-1 gene amplification in a large portion of squamous cell carcinomas, whereas in lung adenocarcinomas the Wig-1 gene was unchanged. Interestingly, strong Wig-1 staining in this cohort correlates to worse prognosis. We think Wig-1 attenuates senescence via downregulating important senescence markers in both tumor and normal cells. Evidence point to Wig-1 playing an inhibitory role on the mRNAs of histone modifying enzymes, thereby acting on well established senescence markers of gene expression and chromatin regulation. Citation Format: Fredrik Jerhammar, Cinzia Bersani, Dijana Djureinovic, Patrick Micke, Klas G. Wiman. The role of the p53 target Wig-1 in senescence and cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 110. doi:10.1158/1538-7445.AM2015-110