tbuckley/cabot-search huggingface dataset:
The effect of quantitative oestrogen receptor expression on recurrence in postmenopausal women with early stage breast cancer.
Authors: J Mansell, IJ Monypenny, AI Skene, P Abram, R Carpenter, JM Gattuso, CR Wilson, WJ Angerson, JC Doughty
Journal: Cancer Research (2009)

Abstract Abstract #1131 Introduction: Approximately 15% of postmenopausal women treated with adjuvant tamoxifen will experience disease recurrence within 5 years. This may reflect resistance of the primary tumour to tamoxifen. We aim to determine if quantitative oestrogen receptor (ER) expression has an effect on the incidence and type of recurrence in this patient group.&amp;#x2028; Methods: All postmenopausal women diagnosed with early stage breast cancer between 1995 and 2001 in 3 hospitals were included. All ER immunohistochemistry was performed on one site by a single pathologist. A percentage of ER expression was assigned to each tumour. Patients were grouped into high ER (≥70% expression) and low ER (&amp;lt;70% expression). Recurrence was defined as distant, locoregional and contralateral. The cumulative risk of recurrence was calculated using the Kaplan-Meier method. Hazard ratios were calculated using Cox regression analysis. Clinical and pathological factors found to be significant on univariate analysis were included in the multivariate analysis.&amp;#x2028; Results: 1563 patients were included in the analysis with a median follow up of 5 years. 190 (12.2%) were classified as having low ER expression. Median age at diagnosis was 62 in the high ER and 59 in the low ER group (p=0.001). There was no significant difference in tumour size, grade and nodal status between ER groups. Low ER expression was associated with significantly higher cumulative recurrence at 5 yrs compared with high ER (17.5% (95% CI 12.0-23.0) vs 11.0% (95% CI 9.2-12.8), p &amp;lt;0.008, log rank test). This difference was only seen in distant recurrence events (15.3% (95% CI 10.0-20.6) vs 8.6% (95% CI 7.0 – 10.2)) with the number of locoregional and contralateral events very similar between the two groups. Using multivariate Cox regression analysis, low ER was a significant predictor of recurrence within 5yrs after adjustment for tumour size, grade, nodal status and mode of presentation (HR 1.64 (95% CI 1.11-2.44), p = 0.014).&amp;#x2028; Conclusions: Postmenopausal women with early stage breast cancer who have tumours with low ER expression are at a significantly increased risk of distant recurrence compared with women with tumours showing high ER expression. This should be considered when making decisions regarding adjuvant treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1131.
Mast Cells Positive to Tryptase Correlate with Angiogenesis in Early Breast Cancer.
Authors: S. Troilo, R. Patruno, N. Zizzo, P. Troilo, A. Catino, C. Gadaleta, G. Ranieri
Journal: Cancer Research (2009)

Abstract Background: Literature data indicate that mast cells (MCs) are involved in tumor angiogenesis due to the release of several pro-angiogenetic factor among which tryptase, a serine protease stored in MCs granules, is one of the most active. In benign breast lesions and in primary breast cancer, tryptase-positive MCs are more numerous as compared to chymase-positive MCs. Recently, it has been demonstrated that tryptase-positive MCs are involved in angiogenesis in sentinel lymph nodes with micrometastases from patients with breast cancer. However no data has been published regarding the correlations between MCs positive to tryptase and angiogenesis in primary breast cancer tissue. In the present study, we have evaluated the correlations between the number of MCs positive to tryptase (MCDPT), the area occupied by MCs positive to tryptase (MCAPT), microvascular density (MVD) and endothelial area (EA) in a series of T1-3, N0-2, MO female breast cancer, by means of immunohistochemistry and image analysis methods.Material and Methods: Bioptic specimens were collected from 88 female breast cancer patients who had undergone breast cancer surgery. For the evaluation of MCDPT, MCAPT, MVD and EA, a three layer biotin-avidin-peroxidase system was utilized. Briefly, six-micrometers thick serial sections of formalin-fixed and paraffin-embedded bioptic tumor samples were obtained. Then sections were microwaved at 500 W for 10 min. and treated with a 3% hydrogen peroxide solution. Sections were incubated with human-specific monoclonal antibodies anti-CD34 (QB-END 10; Bio-Optica Milan, Italy) diluted 1:50 for 1h at room temperature and anti-tryptase (clone AA1; Dako, Glostrup, Denmark) diluted 1:100 for 1h at room temperature. The bound antibody was visualised using biotinylated secondary antibody, avidin-biotin peroxidase complex, and and 3-amino-9-ethylcarbazole. The five most vascularized areas ("hot spot") were selected at low magnification and both individual vessels were counted at x 400 magnification. In serial sections each single tryptase-positive MC was counted. Single brown stained endothelial cells and red MCs positive to tryptase were also evaluated in terms of immunostained area at x 400 magnification.Results: Our data demonstrated a significantly (r= ranging from 0.78 to 0.89; p: ranging from 0.001 to 0.002 by Pearson's analysis respectively) correlation between MCDPT, MCAPT, MVD, EA each to other, whereas no correlation concerning MCDPT, MCAPT, MVD, EA and the main clinical pathological features was found.Discussion: These preliminary results suggest that tryptase-positive MC play a key role in breast cancer angiogenesis and that inhibition of tryptase may be a new antiangiogenic strategy for the treatment of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2159.
SP0168 Win lecture-GOUT and crystal diseases
Authors: A. So
Journal: Annals of the Rheumatic Diseases (2013)

Gout is the articular manifestation of a systemic metabolic disorder – hyperuricemia. The causes of hyperuricemia and its epidemiology have been intensely investigated these last 10 years, and there is an increasing awareness that apart from gout, hyperuricemia is associated with cardiovascular disease and the metabolic syndrome. Recent research has tried to untangle these links and to determine their etiological relationship in man, based on cohort studies and GWAS approaches. A number of novel genes/molecules have been identified and their contribution to the development of gout is being investigated. Persistent hyperuricemia is a major risk factor for the development of gout, an acute inflammatory reaction to MSU crystals deposited in and around the joint. Recent advances in articular imaging by ultrasound and dual energy CT have shown that deposits of MSU are found in the absence of overt inflammation, and suggest that there is a pre-clinical phase of gout. Finally, the therapy of hyperuricemia and of gouty inflammation has seen major drug developments in the last five years. These new drugs should provide the clinician with a larger range of options in the management of gout and hyperuricemia. <h3>Disclosure of Interest</h3> A. So Consultant for: Novartis, Ardea Biosciences, Menarini, Speakers Bureau: Menarini
Abstract 1882: Short- and long-term risk of adenoma recurrence with cigarette smoking: An analysis of the Polyp Prevention Trial and Continued Follow-Up Study
Authors: Adeyinka O. Laiyemo, Chyke Doubeni, Carla D. Williams, Shelly McDonald-Pinkett, Robert E. Schoen, Pamela M. Marcus, Elaine Lanza, Arthur Schatzkin, Duane T. Smoot, Amanda J. Cross
Journal: Cancer Research (2011)

Abstract Background: Prospective studies have evaluated the association between cigarette smoking and colorectal adenoma recurrence within 4 years of follow-up, a relatively short duration. We sought to examine short- and long-term risk of adenoma recurrence in association with cigarette smoking among participants in the Polyp Prevention Trial (PPT), a multicenter, randomized controlled trial that evaluated the effect of a low fat, high fiber, fruits and vegetable diet on the risk of colorectal adenoma recurrence. Methods: A cohort of 774 participants with colorectal adenoma completed a baseline questionnaire including tobacco use and completed the 4-year trial during which they underwent colonoscopy at 1 year and 4 years after enrollment. After the trial was completed, these participants consented to passive follow-up in the Continued Follow-up Study (CFS) during which the colonoscopy reports subsequent to the trial were collected and analyzed. We defined adenoma recurrence as any adenoma detected after the baseline colonoscopy. We used Poisson regression models to evaluate risk of adenoma recurrence up to 4 years (short-term) and up to 12 years of follow-up (long-term). Results: At baseline, 461 (59.6%) participants had a history of smoking: 379 (49.0%) former smokers and 82 (10.6%) current smokers. Mean age of the patients was 59.6 years and 66.2% were males. The mean total duration of follow-up was 8.4 years (range 4.9 – 12.4 years). When compared with never smokers, there was no association between cigarette smoking and adenoma recurrence with either short- or long-term follow-up (Table). Conclusions: Cigarette smoking is not associated with adenoma recurrence in the short- or the long-term. Table: Relative Risk (RR) and 95% confidence interval (CI) for adenoma recurrence during short-term and long-term follow-up according to baseline smoking status Models were adjusted for age, sex, NSAIDs use, BMI and family history of colorectal cancer. 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 1882. doi:10.1158/1538-7445.AM2011-1882
Liver Disease in Adults with Alpha<sub>1</sub>-Antitrypsin Deficiency
Authors: Nils O. Berg, Sten Eriksson
Journal: New England Journal of Medicine (1972)

Examination of hepatic tissue obtained at autopsy (13 cases) and by biopsy (one case) from patients with homozygous alpha1-antitrypsin deficiency showed that the hepatocytes contained periodic-acid-Schiff-positive globular material similar to that seen in infantile cirrhosis with alpha1-antitrypsin deficiency. Five of the adult patients had cirrhosis, and three fibrosis of the liver; of these eight, all over 50 years of age, three also had hepatomas. Twelve of the 13 autopsy cases had either bullous or panacinar emphysema. The findings suggest that in alpha1-antitrypsin deficiency liver disease and emphysema are linked to the same genetic defect.
Hyperbaric-Oxygen Treatment of Multiple Sclerosis
Authors: Boguslav H. Fischer, Morton Marks, Theobald Reich
Journal: New England Journal of Medicine (1983)

Several uncontrolled studies have suggested a beneficial effect of hyperbaric oxygen on multiple sclerosis. We studied 40 patients with advanced chronic multiple sclerosis who were randomly divided into two matching groups. The experimental group received pure oxygen, and the placebo group received a mixture of 10 per cent oxygen and 90 per cent nitrogen; both groups were treated at a pressure of 2 atmospheres absolute for 90 minutes once daily, for a total of 20 exposures. Objective improvement occurred in 12 of 17 patients treated with hyperbaric oxygen and in 1 of 20 patients treated with placebo (P less than 0.0001). Improvement was transient in seven of the patients treated with oxygen and long-lasting in five. Those with less severe forms of the disease had a more favorable and lasting response. At one year of follow-up, deterioration was noticed in 2 patients (12 per cent) in the oxygen group, neither of whom had had an initial response, and in 11 patients (55 per cent) in the placebo group, one of whom had had a positive initial response (P less than 0.0008). Minor ear problems and reversible myopia were the only side effects observed. These preliminary results suggest a positive, though transient, effect of hyperbaric oxygen on advanced multiple sclerosis, warranting further study. This therapy cannot be generally recommended without longer follow-up periods and additional confirmatory experience.
Commons is worried about private finance for NHS New group will strengthen patient involvement in NHS research Special conference will consider future of general practice Transition to new grade must be completed in a year
Authors: L. Beecham
Journal: BMJ (1996)

# Commons is worried about private finance for NHS {#article-title-2}

The all-party House of Commons Treasury select committee has questioned the suitability of the government's private finance initiative (PFI) for health projects. Under the initiative, private finance is raised for large public capital projects, including new hospitals. The select committee report predates the plan for Britain's first £170m PFI hospital to be built from scratch at Norwich (13 April, p 929).

The treasury committee is concerned that those aspects of PFI projects which have a lucrative return will attract investment and would have to be linked to substantial management contracts. The ability of NHS trusts to plan the provision of services could be lost.

While the official policy is that clinical services should not be provided by private finance, the committee heard that the PFI was forcing a false split between clinical and non-clinical services—for example, in the position of the domestic housekeeper hitherto a key member of the clinical team. The committee is concerned that the PFI should not introduce arbitrary demarcations in hospital management.

In written evidence to the committee the BMA warns that while the PFI will not result in the employment of clinicians by private companies, some of them will be supplying clinical services for profit. They may be tempted to cut costs by reducing and putting financial pressure on clinical decisions, leading to ethical problems for doctors.

The BMA states that the greatest instinctive objection to private finance in the NHS is that …
P201 Pneumocystis Jirovecii Prevalence In A Large Uk Adult Cystic Fibrosis Centre
Authors: H. Green, R. Bright-Thomas, P. Barry, A. Horsley, K. Mutton, A. Jones
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> <i>Pneumocystis jirovecii</i> (<i>PJ</i>) is an atypical fungus that causes pneumonia in immunocompromised patients. Its role in patients with cystic fibrosis (CF) is unclear. Its reported prevalence in CF ranges from 1–22% but has never been determined in the UK. Here we present preliminary cross-sectional data from an ongoing study at a UK adult CF centre serving &gt;400 patients, to establish prevalence and potential risk factors for infection. <h3>Methods</h3> Sputum samples were obtained from 100 randomly selected CF outpatients and sent for routine microbiology and <i>PJ </i>DNA PCR assay at enrolment, subsequent visits, and pulmonary exacerbations requiring intravenous antibiotics within 4 months. Data were recorded for demographics, co-morbidities symptom score, spirometry, inflammatory markers, and prophylactic or recent therapeutic antibiotic therapy. Univariate comparisons were made between sputum <i>PJ </i>positive and negative patients. Chi square tests were used for categorical comparisons and independent sample t-tests for continuous independent variables. <h3>Results</h3> Of the 100 patients, 4 of 100 had a positive sputum <i>PJ</i> PCR at baseline. 50 patients had a routine follow up sample between 1 and 4 months: 2 were positive for <i>PJ.</i> 22 patients had a sputum sample analysed at the onset of a pulmonary exacerbation of which 1 was positive for <i>PJ. </i>Hence, a total of 7 of 100 patients had a single positive sample by PCR for <i>PJ.</i> No patient has had &gt;1 positive sample. None of the baseline parameters were significantly different between PJ positive and PJ negative patients at the level p <h3>Conclusion</h3> These results suggest that<i> PJ</i> is not an important infecting pathogen in this UK cohort of CF patients. This may be due to frequent use co-trimoxazole for pulmonary exacerbations and high prevalence of prophylactic macrolide antibiotic therapy at our centre compared to other published studies. These preliminary data were underpowered to accurately compare baseline characteristics between PJ positive and PJ negative patients.
The Risk Factors for Bleomycin Pulmonary Toxicity for Hodgkin Lymphoma and Germ-Cell Tumor: A Single-Center Analysis
Authors: Y. Yamada, N. Matsubara, M. Sasaki, H. Yuasa, Y. Naito, M. Nezu, A. Hosono, H. Mukai, K. Tsukasaki, K. Ito
Journal: Annals of Oncology (2013)
Health Care Reform in the New South Africa
Authors: Solomon R. Benatar
Journal: New England Journal of Medicine (1997)

The social transition which must follow the political transition in South Africa will pose major challenges for many decades. While it clear that inequities must be reduced, it is less clear how to effectively and sustainably achieve that end, especially given current rapid population growth and minimal additional resources in an economy which is growing less rapidly than hoped for by the new government. Health care reform is one of the country's many challenges. This paper provides insight into the shift from the conventional biomedical model of health care to the primary health care approach within a fixed public health budget. Obstacles to change, threats to academic activities, the 1980s and 1990s, political and social transition, health care reform since 1994, academic medicine and medical education, choices facing society, movement from political apartheid to economic apartheid, and public awareness are described.
OC-069 Constitutive Activation of the DNA Damage Response Pathway in Cancer Represents a Deregulated Pathway
Authors: S Din, T Hupp
Journal: Gut (2013)

<h3>Introduction</h3> The DNA damage response (DDR) is an innate cellular response allowing cells to halt the cell cycle and repair DNA damage sustained by activating various mechanisms. The efficacy of conventional cancer treatment modalities is related in their ability to induce DNA damage. Constitutive activation of the ataxia telangectasia mutated (ATM) dependent DDR and repair pathways have been reported in (pre) malignant human tissues and may undermine the efficacy of current cancer therapies. Inhibition of proteins involved in the DDR cascade is an attractive therapeutic concept that may overcome resistance to current cytotoxics and potentiate the effects of radiotherapy. <h3>Methods</h3> A tumour microarray was created using 179 sporadic colorectal cancers; 152 were of the microsatellite stable phenotype. The microarray was interrogated using antibodies against proteins of the DDR signalling cascade. A colorectal cancer cell line model was utilised to asses the functionality of the constitutively activated DNA damage pathway. ATM inhibition in combination with ionising irradiation was analysed in the cell line model using radioactive quantification of DNA synthesis, flow cytometric cell separation, clonogenic survival and immunoblotting. <h3>Results</h3> Phosphorylated Chk2 threonine-68, a surrogate marker of the DDR, was present in 22% of microsatellite-stable colorectal tumours and 33% of tumours with the microsatellite instability phenotype. High p53 staining was present in 53% of microsatellite stable cancers and 26% microsatellite instable cancers. P21-null HCT116 cells display constitutive activation of the ATM DDR but display a defect in the ionising radiation induced S-phase checkpoint, termed radioresistant DNA synthesis. This radioresistant phenotype is associated with increased basal levels of Cdc25A protein, deficient DNA damage-induced degradation of Cdc25A and Chk2 mis-localisation. P21-null HCT116 and SW620 cells, which exhibit basal Chk2 threonine-68 phosphorylation, were unable to abrogate the S-phase checkpoint when treated with an ATM inhibitor, suggesting that the ATM–Chk2 arm is non-functional in these cells: inhibition of ATM did not potentiate the efficacy of ionising irradiation. <h3>Conclusion</h3> In a colorectal cancer cell line model constitutive activation of the ATM DDR pathway reflected a non-functional pathway and inhibition of ATM in these circumstances was unable to potentiate the efficacy of ionising irradiation. Basal Chk2 threonine-68 phosphorylation in colorectal cancer may reflect a deregulated ATM DDR pathway and/or checkpoint adaption. A predictive model is proposed that integrates functionality of the ATM-Chk2 axis, p53 mutation status and defects in DNA repair pathways when considering ATM inhibitor therapy. <h3>Disclosure of Interest</h3> None Declared
Abstract 5000: Epigenetic de-silencing of Glutathione s-transferase pi by tumor suppressive maspin
Authors: Xiaohua Li, Elisabeth Heath, Wael A. Sakr, Shijie Sheng
Journal: Cancer Research (2010)

Abstract Abstract: Loss of expression of the GST pi isoform due to DNA hypermethylation-mediated epigenetic silencing is one of the most common molecular events in precancerous and cancerous lesions of human prostate. Our previous studies demonstrated that tumor suppressive maspin, an endogenous inhibitor of histone deacetylase 1, could up-regulated GST activity and reduced reactive oxygen species (ROS) generation in response to oxidative stress treatment. We confirmed that maspin restored GST pi expression in maspin transfected prostate cancer cell line DU145. Conversely, maspin knocking down by siRNA in PC3 cells led to reduced GST pi expression. We further investigated the possibility that the epigenetic regulation by DNA-methylation and histone deacetylation were coupled dynamic processes that HDAC inhibition by maspin alone was sufficient to reverse the DNA-methylation silencing effects. Using methylation-specific polymerase chain reaction (M-PCR), DNA demethylation in GST pi promoter was detected only in maspin-expressing cells. Chromatin immunoprecipitation (ChIP) assay showed that a significant higher level of acetylated histone 3 was associated with the GST pi promoter DNA complex. In the same DNA complex from maspin transfected cells, less DNA methylation transferase (DNMT1) and methyl-CpG-binding domain (MBD2/3) proteins were detected as compared to that from the mock control cells. It was noted that in DU145-derived transfected cells, maspin simultaneously restored GST pi expression and sensitized tumor cells to drug-induced apoptosis, while overexprssion of GST pi alone in LNCaP prostate cancer cells conferred resistance to oxidative stress in cell death, HIF-1α induction, and phosphorylation of histone 2A.X. These data suggest that, as an epithelial-specific HDAC1 inhibitor, maspin may function to maintain the epithelial tissue homeostasis through balancing the GST pi-dependent detoxification and HDAC1 inhibition-dependent apoptosis sensitivity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5000.
The Clinical Utility of Tc-99m–Labeled Tin Colloid in the Diagnosis of Extramedullary Hematopoiesis
Authors: URVI JOSHI, VINCE A. PARTAP, CHRIS RUSH
Journal: Clinical Nuclear Medicine (2000)

A case is presented in which Tc-99m–labeled tin colloid scintigraphy was used to confirm the presence of extramedullary hematopoiesis in a large pelvic mass in an 83-year-old man with sideroblastic anemia and symptoms suggestive of renal colic.
Guanidine Derivatives in Medicine
Authors: Philip R. Steinmetz, Christine Balko, Frank Davidoff
Journal: New England Journal of Medicine (1973)

FIFTY years have passed since the introduction of insulin into medicine. It is not widely known that guanidine derivatives were first used in the therapy of diabetes at about the same time, and that the effects of guanidine in a biologic system were first described nearly 100 years ago.1 Over the years, a wide variety of guanidine derivatives have become important investigational tools, as well as major therapeutic agents. Table 1 shows some of these compounds and the extensive range of their activities and uses. It is tempting to conclude that the common structural feature, the guanidine residue, confers no more specificity . . .