tbuckley/cabot-search huggingface dataset:
Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in <i>BRCA1/2</i> Mutation Carriers
Authors: Alexandra J. van den Broek, Laura J. van ’t Veer, Maartje J. Hooning, Sten Cornelissen, Annegien Broeks, Emiel J. Rutgers, Vincent T.H.B.M. Smit, Cees J. Cornelisse, Mike van Beek, Maryska L. Janssen-Heijnen, Caroline Seynaeve, Pieter J. Westenend, Jan J. Jobsen, Sabine Siesling, Rob A.E.M. Tollenaar, Flora E. van Leeuwen, Marjanka K. Schmidt
Journal: Journal of Clinical Oncology (2015)

To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations.A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses.After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 [95% CI, 2.41 to 4.55; P < .001] and 2.17 [95% CI,1.22 to 3.85; P = .01], respectively). Ten-year cumulative CBC risks were 21.1% (95% CI, 15.4 to 27.4) for BRCA1, 10.8% (95% CI, 4.7 to 19.6) for BRCA2 mutation carriers and 5.1% (95% CI, 4.5 to 5.7) for noncarriers. Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively.Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.
CD20-Negative Relapse After <sup>131</sup>I–Anti-CD20 Therapy
Authors: P. Venugopal, W. T. Leslie, T. O'Brien, S. A. Gregory
Journal: Journal of Clinical Oncology (1999)

Article Tools Correspondence Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.11.3692 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10550173 CD20-Negative Relapse After 131I–Anti-CD20 Therapy P. VenugopalxP. VenugopalSearch for articles by this author , W. T. LesliexW. T. LeslieSearch for articles by this author , T. O'BrienxT. O'BrienSearch for articles by this author , S. A. GregoryxS. A. GregorySearch for articles by this author Show More Rush Cancer Institute, Rush Presbyterian St Luke's Medical Center, Chicago, IL https://doi.org/10.1200/JCO.1999.17.11.3692 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Familial chronic lymphocytic leukemia in two siblings with ATM/13q14 deletion and a similar pattern of clonal evolution
Authors: I V Kostopoulos, A A Tsakiridou, D Pavlidis, A Megalakaki, S I Papadhimitriou
Journal: Blood Cancer Journal (2015)

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in Western countries and accounts for 34% of adult leukemias in the United States1. Although the etiology of CLL remains unknown, there is increasing evidence for the pathogenetic role of inherited factors.2 The familial subtype of the disease is distinguished from sporadic CLL by the presence of at least one affected relative, with the same or a different chronic lymphoproliferation. According to the usual approach, these families have been analyzed to detect linkage, based on the hypothesis of coinheritance of genetic markers. However, due to the small pedigree sizes, these studies have proved inconclusive in determining any specific gene or non-coding region related to the pathophysiology of CLL.3, 4 Moreover, several reports on such cases reveal a significant biologic heterogeneity of familial CLL and indicate that there is no consistent pattern of pathogenesis that would suggest a simple mode of transmission. In this report, we present two siblings diagnosed with CLL, with common chromosomal aberrations and an almost identical pattern of clonal evolution, which is unusual among all published familial cases.
15-Lipoxygenase metabolites modulate proliferative and metastatic signal transduction pathways in human breast carcinoma cells
Authors: Wayne Glasgow, Erika Noble
Journal: Cancer Research (2007)

4476   In addition to serving as potent inflammatory mediators, specific metabolites of arachidonic and linoleic acid are implicated in modulating cell growth, carcinogenesis, and metastasis. In the human breast carcinoma cell line BT-20, we characterized extensive 15-lipoxygenase (LOX)-1 metabolism of linoleic acid to 13-hydroxyoctadecadienoic acid (HODE) by HPLC analyses, RT-PCR, Northern and Western blots. In addition to expression in cell lines, we found enhanced expression of 15-LOX-1 in 15/39 human infiltrating ductal carcinoma breast tissue biopsies. Inhibition of 15-LOX activity blocked both 13-HODE biosynthesis and cellular response to EGF. 13-HODE (1 μM) was found to enhance p42/44 MAP kinase phosphorylation and activity, resulting in augmented mitogenic signaling. In MDA-MB-435 human breast cancer cells, 15-hydroxyeicosatetraenoic acid (HETE), derived from 15-LOX-2 pathways, stimulated cell adhesion to type IV collagen through activation of p38 MAP kinase. Regulation of cell-cell and cell-matrix adhesion plays a key role in the metastatic process. This 15-HETE stimulation involved activation of upstream TGFβ-activated protein kinase (TAK1) and MAP kinase 6. Transfection of cells with dominant negative TAK1 inhibited arachidonic acid stimulation of p38 MAP kinase phosphorylation. These data demonstrate that specific lipid mediators of the 15-lipoxygenase pathways are involved in modulation of signal transduction pathways related to breast cancer cell growth and metastasis and implicate 15-lipoxygenase as a potential therapeutic target.
Remodulation of the tumor microenvironment by regulatory T cells
Authors: Chang Liu, Maria Chikina, Creg J Workman, Dario AA Vignali
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The tumor microenvironment is a complex system, which is composed of various types of non-tumor cells including stromal fibroblasts, the blood and lymphatic vascular networks, the extracellular matrix and notably, the infiltrating immune cells. Regulatory T cells (Treg cells) play
Weights and measures: are bariatric surgery guidelines realistic?
Authors: Youssof Oskrochi, Azeem Majeed, Graham Easton
Journal: Journal of the Royal Society of Medicine (2015)

or metabolic syndrome may be considered for bariatric surgery, if deemed beneficial. The publication of these guidelines will inevitably mean more people will become eligible for surgery, but will these guidelines be practical; and can health services cope with the potential demand for bariatric surgery? The proportion of people with class III obesity (body mass index 40), who are automatically eligible for surgery, has been steadily increasing in the UK for many years and currently stands at 1.7% of men and 3.1% of women, with one projection indicating that this could reach 3% of men and 6% of women by 2030. 6 Furthermore, the number of people eligible for bariatric surgery in the UK is likely to have been underestimated 7 ; concurrent data from
Formation and characterization of a novel 4-hydroxyestradiol-formamidopyrimidine adduct
Authors: Leslie Bransfield, Shelly Odwin, James Yager, John Groopman
Journal: Cancer Research (2008)

4339  A major risk factor for breast cancer is the endogenous hormone, estrogen. Estrogen mediated carcinogenesis can involve its binding to estrogen receptors stimulating cell proliferation and its oxidative metabolism to catechols and then quinones which can form covalent adducts with DNA. Estrogen quinone-DNA adducts are also potential biomarkers for risk assessment of cancer development. The ability to quantitatively measure these adducts and assign a risk based on the levels of adducts could lead to earlier detection and possible prevention strategies. The estradiol (E2) quinone metabolites are electrophilic compounds that react with DNA to form both stable and depurinating adducts. The quinone derived from 4-hydroxyestradiol can react with DNA to form adenine and guanine adducts which depurinate from DNA. These initial N7-N9 doubly substituted E2 quinone-guanine adducts place a localized positive charge on the imidazole ring of the pyrimidine facilitating destabilization of the glycosidic bond resulting in depurination. Alternatively, the positive charge can also facilitate ring opening of the imidazole ring leading to a stable formamidopyrimidine (fapy) adduct. The in vitro half-life of the unstable 4-hydroxyestradiol-N7-deoxyguanosine (4-OHE2-N7-dG) adduct was reported to be 6.5 hrs which sufficient for fapy production. We conducted studies to determine if 4-OHE2-N7-dG is converted to its fapy derivative (4-OHE2-fapy-dG). Analysis by mass spectrometry revealed an m/z of 572.4 which corresponds to 4-OHE2-fapy-dG. Upon ms/ms analysis, an m/z of 455.2 was found corresponding to loss of the deoxyribose moiety. Additional analysis by ms3 revealed fragments with m/z 167.9 and 140.1 corresponding to fapyG and loss of CO from fapyG respectively. These data confirm formation of 4-OHE2-fapy-dG in reactions involving the nucleoside. Further studies to investigate the possible formation of this adduct in calf thymus DNA and DNA from cultured rat hepatocytes treated with E2 are underway to determine if there is any biological significance to this novel estrogen adduct derivative. Confirmation of the fapy estrogen adduct in a biological system will add another piece to the puzzle in the complex metabolic profile of estrogen.  As mentioned, estrogen quinones can react with DNA to form depurinating adducts which are potential biomarkers for risk assessment since they are a direct measure of DNA damage. Efforts have focused on developing a method to quantitatively measure E2-guanine adducts in hepatocyte media from ACI and Sprague-Dawley (SD) rats. ACI rats are sensitive to estrogen induced tumors while SD rats are not. Expectations are the ACI rat hepatocytes will produce more estrogen-guanine adducts compared to the SD rat hepatocytes when treated with E2. These experiments will give insight as to whether or not E2-guanine adducts are biomarkers of estrogen induced tumorgenesis and ultimately carcinogenesis.
The Origin of Tissue-Resident Macrophages: When an Erythro-myeloid Progenitor Is an Erythro-myeloid Progenitor
Authors: Elisa Gomez Perdiguero, Kay Klapproth, Christian Schulz, Katrin Busch, Marella De bruijn, Hans-Reimer Rodewald, Frederic Geissmann
Journal: Immunity (2015)
Abstract 16826: Older Adults With Unrecognized Myocardial Infarction Have Increased Risk of Heart Failure
Authors: Jie J Cao, Erik B Schelbert, Thor Aspelund, Peter Kellman, Gudmundur Thorgeirsson, Sigurdur Sigurdsson, Gudny Eiriksdottir, Lenore J Launer, Tamara B Harris, Vilmundur Gudnason, Andrew E Arai
Journal: Circulation (2014)

Background: Heart failure (HF) is an important cause of morbidity and mortality in older populations. In this study we characterized the risk of HF in relation to unrecognized myocardial infarction (UMI) among those without prevalent cardiovascular disease (CVD) in an elderly cohort. Methods: The study subjects were the participants of the Iceland_MI substudy of the Age, Gene/Environment Susceptibility-Reykjavik study, a population based prospective study of older adults. We excluded subjects with prevalent CVD defined as a history of recognized MI, acute coronary syndrome, HF, cardiac arrest, ventricular arrhythmia and stroke. Left ventricular ejection fraction (LVEF) was assessed using cine MRI and UMI was determined by late gadolinium enhancement imaging. Incident HF was adjudicated based on medical records. Results: Of the 701 subjects analyzed, the mean age was 77±5 years, 57% were female and 34% diabetic. The prevalence of UMI was inversely related to the LVEF, 50%, 24% and 10% for LVEF≤45% (n=26) L...
Erectile dysfunction (ED) in successfully treated lymphoma patients
Authors: S. Aksoy, M. Dinçer, S. Kilickap, H. Harputluoglu, Ö. Dizdar, B. Akdogan, H. Özen, M. Erman, I. Celik
Journal: Journal of Clinical Oncology (2006)

18570 Background: Information on male potency in lymphoma survivors is insufficient. In this study, we assessed male sexual function in successfully treated lymphoma patients (pts). Methods: Fifty-nine pts treated for Hodgkin’s (HL) or non-Hodgkin’s lymphoma (NHL) with chemotherapy ± radiotherapy were recruited. Pts older than 55 years and those with a history of pelvic/inguinal radiotherapy or surgery were excluded. Study pts had to be disease-free and off-treatment for at least 6 months at the time of evaluation. Pts completed a survey questionnaire that consisted of demographic characteristics, risk factors for ED and the International Index of Erectile Function (IIEF) to assess their current level of sexual function. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were also determined. Results: The mean age of the 59 pts was 40.2 ± 11.0 (range, 18–55 years). Thirty-eight (64.4%) had HL and 21 (35.6%) NHL. The mean interval between the end of active treatment and study evaluation was 7.7 years (range: 10 mths to 20 yrs). According to the IIEF score, 61.0% had some degree of ED (IIEF score &lt;26): 33.9% had mild ED (IIEF score 17–25), 15.2% moderate ED (IIEF score 11–16) and 11.9% severe ED (IIEF score 6–10). Mean total scores of sexual desire, sexual satisfaction, orgasm and overall satisfaction domains of IIEF were significantly lower in pts with ED than those with normal ED (26.0 ± 1.8 and 39.0 ± 0.8, respectively; p &lt; 0.001). Nine (18.4%) of 49 pts had an elevated FSH, 7 (14.2%) had elevated LH, and 3 (6.1%) had decreased testosterone levels. These hormonal disturbances did not affect the presence of ED and its severity. Six (10.2%) pts had hypertension and 3 (5.1%) had diabetes mellitus. Forty (57.6%) pts were ever-smokers, 29 (49.2%) were overweight or obese (BMI &gt;25), but none had coronary artery disease. These risk factors did not statistically affect the presence of ED or its severity in our pts. Conclusions: These findings suggest that diagnosis and treatment of lymphoma may be a risk factor per se for the development of ED. Therefore, the underlying pathology, either organic or psychological, remains to be defined. Clinicians should be aware of this problem in lymphoma survivors and offer these pts adequate treatment options. No significant financial relationships to disclose.
Abstract 11223: Hydrochlorothiazide Use is Independently Associated With a Decreased Risk of New Atrial Fibrillation in Hypertensive Patients With Electrocardiographic Left Ventricular Hypertrophy
Authors: Peter M Okin, Kristian Wachtell, Sverre E Kjeldsen, Richard B Devereux
Journal: Circulation (2014)

Background: High and even upper-normal blood pressure (BP) are predictors of incident atrial fibrillation (AF) and we have recently demonstrated that more aggressive BP control is associated with a lower risk of new AF. Previous study has demonstrated that hydrochlorothiazide (HCTZ) use is independently associated with greater left atrial size reduction in hypertensive patients. However, whether HCTZ use is associated with a lower incidence of AF independent of BP effects is unclear. Methods: Risk of new-onset AF was examined in relation to in-study HCTZ use in 8704 hypertensive patients with ECG LVH with no history of AF, in sinus rhythm on their baseline ECG, with baseline data on HCTZ use, who were randomly assigned to losartan- or atenolol-based treatment with additional protocol-based use of HCTZ as needed to lower BP. Results: During 4.7±1.1 years follow-up, new-onset AF was diagnosed in 691 patients (7.9%) and 6,932 (79.6%) were treated with HCTZ at some time. In univariate Cox analysis, in-study H...
Abstract 16131: Novel Magnetic Resonance Wave Intensity Analysis in Pulmonary Hypertension
Authors: Michael A Quail, Daniel S Knight, Jennifer A Steeden, Liesbeth Taelman, Shahin Moledina, Andrew M Taylor, Patrick Segers, J. Gerry Coghlan, Vivek Muthurangu
Journal: Circulation (2014)

Background: Pathological pulmonary wave reflections (WR) are a potential hemodynamic biomarker for pulmonary hypertension (PH). WR can be quantified using wave intensity analysis (WIA), typically utilizing simultaneous invasive pressure and velocity measurements. In this study we reformulated WIA to use CMR area and flow to measure reflections non-invasively. We hypothesized that this method could detect differences in WR in PH patients compared to healthy controls and could also differentiate certain PH subtypes. Methods: 20 patients with PH (35% CTEPH), mean age 54years (75% female) and 10 healthy controls, 47years (60% female) were recruited. Branch pulmonary artery (PA) flow volume (Q) and area curves (A) were used to measure wave intensity ( dI ), defined as, dI =[[Unable to Display Character: &amp;#8710;]]Ax[[Unable to Display Character: &amp;#8710;]]Q and dI ± =± c /4 [[[Unable to Display Character: &amp;#8710;]]A± [[Unable to Display Character: &amp;#8710;]]Q/ c ] 2 , where c =wave-speed. Data were acquired using a retrospectively gated, respiratory navigated, golden-angle, 10.5ms temporal resolution, phase-contrast MR sequence. All patients also underwent right heart cardiac catheterization for pressure and vascular resistance (PVR) measurement, median interval 6 days (IQR 2-11days). The presence of proximal clot in CTEPH patients was determined from contemporaneous CT/angiographic data. Results: A backwards-travelling compression wave (BCW) was present in both left and right PAs of all PH patients, but was absent in all controls ( p =6e -8 ). A backwards-travelling expansion/suction wave was present in the 19/20 branch PAs of controls, and only 4/40 PAs in patients ( p &lt; 0.0001). The area under the BCW was associated with a sensitivity of 100% (95% CI 63-100%) and specificity of 91% (95% CI 75-98%) for the presence of clot in the proximal pulmonary arteries of patients with CTEPH. Conclusions: Noninvasive pulmonary WIA accurately delineates pulmonary vascular health and disease. The main findings of this study were: i) There was a significant difference in WIA metrics between patients and controls, in particular, the presence of a BCW was specifically associated with the presence of PH; and ii) The magnitude of the BCW area showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the non-invasive assessment of PH.
Evidence is insufficient to recommend e-cigarettes for quitting, US committee concludes
Authors: I. Torjesen
Journal: BMJ (2015)

There are not enough data on the effectiveness of electronic cigarettes to determine whether the devices can help smokers quit, the US Preventive Services Task Force has concluded.1

The Task Force, which makes recommendations on the effectiveness of preventive healthcare services such as screening, counselling, and use of drugs, issued its draft evaluation of tobacco smoking cessation in adults and pregnant women on 5 May. The evaluation said that “the current evidence is insufficient to recommend electronic nicotine delivery systems (ENDS) for …
Spontaneous Disseminated Squirrel Fibroma
Authors: Shively, James N., Moe, Kathleen K., Woolf, Alan, King, John M.
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Spontaneous Disseminated Squirrel Fibroma Get access James N. Shively, James N. Shively Department of Pathology, New York State Veterinary College, Cornell University, Ithaca, New York 14850 Search for other works by this author on: Oxford Academic PubMed Google Scholar Kathleen K. Moe, Kathleen K. Moe Department of Pathology, New York State Veterinary College, Cornell University, Ithaca, New York 14850 Search for other works by this author on: Oxford Academic PubMed Google Scholar Alan Woolf, Alan Woolf Department of Pathology, New York State Veterinary College, Cornell University, Ithaca, New York 14850 Search for other works by this author on: Oxford Academic PubMed Google Scholar John M. King John M. King Department of Pathology, New York State Veterinary College, Cornell University, Ithaca, New York 14850 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 3, September 1972, Pages 919–922, https://doi.org/10.1093/jnci/49.3.919 Published: 01 September 1972 Article history Received: 18 July 1972 Accepted: 21 July 1972 Published: 01 September 1972
EU court adviser upholds standard tobacco packaging law
Authors: Clare Dyer
Journal: BMJ (2015)

A European Union law requiring all member states to introduce standardised packaging for cigarettes is valid, a senior legal adviser to the European Court of Justice told the court on 23 December in the latest blow for the tobacco industry.

Opinions from the court’s advocates general are not binding but are usually followed by the judges’ rulings, which are. The judges’ rulings in this case are expected in four to six months.

If the judges agree with the German advocate general, Juliane Kokott, member states will be able to …
P-176 Nabpaclitaxel plus gemcitabine as induction chemotherapy (CT) followed by chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC)
Authors: L. Foltran, G. Boz, G. Lo Re, R. Innocente, D. Tonin, A. De Paoli, G. Tosolini, A. Del Conte, S. Saracchini, P. Sandri
Journal: Annals of Oncology (2015)
P0725 : Lipidomics analysis of fasting serum identifies novel lipid biomarkers specific for HCV genotype 3 and genotype 1 chronic hepatitis C virus infection
Authors: D.A. Sheridan, M. Gomez Romero, S. Bridge, M. Crossey, I.T. Shawa, D. Neely, D. Felmlee, E. Holmes, M. Bassendine, S. Taylor-Robinson
Journal: Journal of Hepatology (2015)