tbuckley/cabot-search huggingface dataset:
Abstract 1777: Antitumor effect of PM01183 in a human pancreatic adenocarcinoma orthotopic model
Authors: M Virtudes Cespedes, M José Guillén, Ramon Mangues, Alberto Gallardo, P Alamo, I Casanova, Carmen Cuevas, Pablo Aviles
Journal: Cancer Research (2012)

Abstract Background: Pancreatic ductal adenocarcinoma is the fourth cause of death in the Western world and, despite the advances in cancer therapies, limited therapeutic benefit (palliating symptoms, better quality of life) may be offered to patients: the overall 5-year survival rate remains &amp;lt; 5%. PM01183 is a new synthetic tetrahydroisoquinoline alkaloid that binds to selected DNA sequences and promotes apoptosis by inducing double-strand breaks at nanomolar concentrations. Confirmed antitumor clinical activity was observed at the recommended dose level of PM01183 in the first-in-human Phase I study in patients with advanced/refractory solid tumors. Currently, PM01183 clinical development includes Phase II single agent trials (pancreas, breast and platinum-resistant/refractory ovarian) as well as Phase I trials in combination (with doxorubicin and gemcitabine) and in advanced acute leukemia. The in vivo antitumor activity of PM01183 was investigated in the human NP9 pancreatic orthotopic model Material and Methods: Athymic nude female mice were orthotopically implanted with luciferase-expressing NP9Luc tumors. Fifteen days after implantation, tumor bearing mice were randomly allocated (N=12 /group) into either PM01183 (at 0.18 mg/kg), gemcitabine (at 180 mg/kg) or control (placebo) groups. Treatments were initiated (Day 0) and administered for 3 consecutive weeks (q7dx3; days 0, 7, 14). Response to treatment was assessed on Day 7 (short-term) by bioluminescence imaging (BLI), and by survival evaluation (long-term): mice were sacrificed when their tumor diameters reached ca. 2 cm or when they became moribund. Statistical differences between groups were determined using two-tailed Mann-Whitney U test and by analysis of the Kaplan-Meier curve. Results: Results showed that PM01183 (q7dx3 at 0.18 mg/kg) induced statistically significant tumor reduction compared to placebo-treated animals by BLI analysis (P= 0.006) on Day 7. Reductions in tumor size were associated to changes in survival median times: PM01183 treatment significantly increased the survival time compared to either gemcitabine- (P= 0.003) or placebo-treated (P= 0.0001) animals. Conclusion: PM01183 demonstrated in vivo antitumor activity in a human pancreatic orthotopic model (NP9), as reflected by metabolic, size-related and survival rate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1777. doi:1538-7445.AM2012-1777
976 CENTRILOBULAR CHANGES ARE KEY HISTOLOGICAL FINDINGS FOR SEGREGATING CASES OF DE NOVO AUTOIMMUNE HEPATITIS AFTER LIVER TRANSPLANTATION
Authors: M. Sebagh, A. Coilly, M. Castillo-Rama, A. Dos Santos, V. Delvart, C. Johanet, A.-M. Roque-Afonso, B. Roche, J.-C. Duclos-Vallee, D. Azoulay, D. Samuel, A.-J. Demetris
Journal: Journal of Hepatology (2012)
Half the 14 million people in poorer countries who need antiretrovirals get them
Authors: A. Gulland
Journal: BMJ (2011)

Countries must stand by their pledge to increase their funding for combating the HIV and AIDS epidemic to build on dramatic progress made in recent years, a report by the United Nations says.

In his introduction to the report, released a week before world AIDS day on 1 December, Michel Sidibe, executive director of UNAIDS, the joint UN agency on HIV and AIDS, focused on the success of the international response to the HIV epidemic: “Just a few years ago, talking about ending the AIDS epidemic in the near term seemed impossible, but science, political support and community responses are starting to deliver clear and tangible results.”

The report says that the annual number of people dying of AIDS related illnesses fell to 1.8 million in 2010, down from a peak of 2.2 million in the middle of the last decade. A total …
Neuraminidase Activity and Free Sialic Acid Levels in the Serum of Patients with Acute Poststreptococcal Glomerulonephritis
Authors: Bernardo Rodríguez-Iturbe, Vishwa N. Katiyar, Jesús Coello
Journal: New England Journal of Medicine (1981)

It has been suggested that in acute poststreptococcal glomerulonephritis, streptococcal neuraminidase may remove sialic acid from some normal plasma or tissue component, thus rendering it antigenic. We therefore investigated serum neuraminidase activity and serum and urinary free neuraminic acid levels, using the thiobarbituric acid method, in 39 patients with acute poststreptococcal nephritis. Serum neuraminidase activity was found in eight patients, and increased thiobarbituric acid-reactive material (presumed to be free neuraminic acid on the basis of absorption-spectrum similarity) was found in 28 patients. Serial determinations in 21 patients indicated that neuraminidase activity was present only initially and that free neuraminic acid levels decreased with time, usually becoming undetectable after four weeks. Determinations in patients with other renal and nonrenal diseases suggested that the findings were characteristic of poststreptococcal nephritis. Urinary neuraminic acid levels were unrelated to serum levels and were not markedly different between patients and normal subjects. These data suggest a role for neuraminidase activity in acute poststreptococcal nephritis, but they do not indicate whether it is primary or secondary. (N Engl J Med. 1981; 304:1506–10.)
Abstract 2127: Screening of the <i>PALB2</i> gene in 57 Chilean patients with hereditary breast cancer
Authors: Carolina Alvarez, Patricia Gajardo, Alejandro Sánchez, Teresa Tapia, Cristobal Herrera, Felipe Benavides, Mauricio Camus, Manuel Alvarez, Pilar Carvallo
Journal: Cancer Research (2010)

Abstract PALB2 is essential for the nuclear localization and function of BRCA2. Together, these proteins participate in DNA damage repair by Homologous Recombination (HR). It has been described, that women carrying mutations in PALB2 gene have greater susceptibility to develop breast cancer than non-carriers. In order to determine the presence of PALB2 mutations among Chilean breast cancer patients, we analyzed through Single Strand Conformomer Polymorphisms analysis (SSCP) and Direct Sequencing, 57 Chilean families with breast cancer, that are not carriers of BRCA1 or BRCA2 mutations. We found 11 sequence alterations: 8 exonic, 2 intronic, and 1 in 5′UTR region. Among these, 2 are novel and found for the first time in our study: an intronic deletion c.3351-66delT and an exonic silent variant p.G752G. With the purpose of assessing the effect of each aminoacidic variant on PALB2, we use the software Polyphen, showing that the missense variant p.G998E may affect the function and/or structure of PALB2 protein. We also evaluated a possible effect of some silent variants on splicing using the software ESEfinder, finding that the 5′UTR nucleotide substitution c.1-47G&amp;gt;A, and the silent variant p.T1100T affect the binding of SR proteins to Exonic Splicing Enhancer sequences. The 5′UTR variant and two aminoacidic substitutions, p.G998E and p.Q559R, were screened in 200 healthy controls, finding no association to hereditary breast cancer. Our work is the first mutation screening study for PALB2 gene among families with breast cancer in a Latin American population. Financed by FONDECYT 1080595 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 2127.
Commentary: What Can Be Learned from Studying Asian Health Problems?
Authors: Philip S. Chen
Journal: Environmental Health Perspectives (1982)

National Institutes of Health, owing to its broad mandate to pursue and support acquisition of knowledge in biomedicine, is very much concerned with' any investigations leading to better understanding of the causes and control of human diseases. One approach is to study health and illness in special subsets of the United States population and of populations in foreign countries. In this paper, I shall touch briefly on a number of health problems and disease-oriented research topics looked at from the special perspective of Asian and Asian-American populations, hopefully to sensitize perceptions about the contributions that such studies can make to our total understanding of how best to achieve health and conquer disease.  new goal of the World  Organization (WHO) is Health for all by the year 2000. The aim is to enable all people of the world to attain an acceptable level of health and to lead a socially and economically productive life. (1).
Abstract 3455: Comparison of expression profiles of pediatric high and low grade brainstem gliomas to pediatric supratentorial high grade astrocytomas
Authors: Pawel Buczkowicz, Ute Bartels, Andrew Morrison, Eric Bouffet, Uri Tabori, Cynthia Hawkins
Journal: Cancer Research (2011)

Abstract Diffuse intrinsic pontine gliomas (DIPG) are one of the most devastating pediatric malignancies and currently the number one cause of brain tumor related death in children with a 10-12 month median survival. Despite this very little is understood about the biology of these tumors. We have already shown potential novel therapeutic targets for DIPG using high-resolution SNP-based analysis. We performed high resolution genetic analysis using whole-genome single-nucleotide polymorphism (SNP) arrays (Affymetrix 500K and 6.0) on post mortem tumor with matched normal brain samples (n=9) and surgical samples (n=2) for a series of DIPG patients as well as pediatric supratentorial high grade astrocytomas (sHGA, n=20). Here we extend our initial study to include expression array analysis, amalgamating the datasets to generate a more complete understanding of the genetic alterations underlying brainstem gliomas. Expression profiling using Illumina HumanHT-12 arrays was conducted on 26 high grade brainstem gliomas, including 23 DIPGs, 51 low grade brainstem gliomas and 30 supratentorial high grade astrocytomas. Expression profiles highlighted the distinctiveness of DIPGs when compared to high grade supratentorial astrocytomas. Analysis resulted in two groups of DIPGs when clustering based on most significant differentially expressed genes (p &amp;lt; 0.005) with one group being more similar to pediatric low grade brainstem gliomas and the other distinct from both the supratentorial high grade tumors and other brainstem gliomas. This data will increase our understanding of brainstem glioma biology, information crucial to the development of agents targeted more specifically towards this devastating disease. 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 3455. doi:10.1158/1538-7445.AM2011-3455
Abstract 982: Transgenic expression of NSAID-activated gene-1 (NAG-1) protects mice from high fat diet-induced obesity
Authors: Jong-Sik Kim, Kaliopi Chrysovergis, Justin Kosak, Grace Kissling, Thomas Eling
Journal: Cancer Research (2011)

Abstract Previously, we generated transgenic mice which over-express human NAG-1/GDF15 gene. These mice are resistant to the development of colorectal cancer and have reduced responses to inflammatory stimuli. In the present study, we observed that NAG-1 transgenic mice (NAG-1 Tg) are smaller and leaner than their wild-type counterparts and have less abdominal fat despite comparable food intake. Interestingly, the transgenic mice have lower circulating levels of the inflammatory adipokine, leptin, and lower expression in abdominal fat, the major source of leptin. Placed on a high fat diet (60% fat), body weight gain in NAG-1 Tg mice is very small or negligible compared to wild-type mice. Analysis of the metabolic activity showed that NAG-1 Tg mice on the high fat diet have higher energy expenditure than WT mice. In addition, global gene expression profiling analysis showed that expression of several genes involved in lipid metabolism were significantly down-regulated in the liver of NAG-1 Tg mice. Real-time PCR analysis confirmed decreased expression of genes such as Cidea, Cidec, Mogat1, CD36, and Apoa4, while the expression of SIRT-1 and phosphorylated SIRT-1 was not altered in the NAG-1 Tg mice. Taken together, our data indicate increased energy expenditure and decreased expression of lipid metabolism genes have pivotal roles for the lower observed abdominal fat levels. Furthermore, lower leptin levels, a critical mediator of intestinal inflammation, found in NAG-1 transgenic mice, may contribute to lower intestinal tumor growth and reduced inflammatory responses reported for the NAG-1 Tg mice. 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 982. doi:10.1158/1538-7445.AM2011-982
Limited Occurrence of the Midlethal Effect in Mice
Authors: D. E. UPHOFF
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Limited Occurrence of the Midlethal Effect in Mice Get access DELTA E. UPHOFF DELTA E. UPHOFF Division of Cancer, Biology and Diagnosis National Cancer InstituteBldg. 10, Rm. 6B18, National Institutes of Health Bethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 20, 21 December 1988, Page 1641, https://doi.org/10.1093/jnci/80.20.1641 Published: 21 December 1988
Simultaneous Administration of CPT-11 and Fluorouracil: Alteration of the Pharmacokinetics of CPT-11 and SN-38 in Patients With Advanced Colorectal Cancer
Authors: Y. SASAKI, Y. SHIMADA, A. OHTSU, K. ONO, N. SAIJO
Journal: JNCI Journal of the National Cancer Institute (1994)

epidemiologic and experimental studies, affords the opportunity to better design our future research to elucidate the underlying mechanisms of breast cancer.In view of the "far-reaching implications for public health," it would be prudent to pursue these ideas.
SP0082 Smoking as Predictor and as a Confounder in RMDs
Authors: L. Alfredsson
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The current knowledge concerning the association between smoking and risk of rheumatic diseases will be reviewed, especially with regard to rheumatoid arthritis and systemic lupus erythematosus. The role of smoking as a confounder in the context of rheumatic disease will be discussed. What is the magnitude of bias when not adjusting for smoking when investigating associations between smoking-associated exposures and risk of rheumatic disease? Does it suffice to adjust for ever/never smoking when investigating associations between smoking-associated exposures and risk of rheumatic disease? What is the magnitude of residual confounding in comparison with adjusting for cumulative dose of smoking? Questions like these will be answered during the presentation. <h3>Disclosure of Interest</h3> None Declared
Abstract 732: Overexpression of the basic helix-loop-helix protein DEC1 induces cellular senescence and is related to better survival in esophageal squamous cell carcinoma
Authors: Qing Xu, Peiqing Ma, Chenfei Hu, Lechuang Chen, Liyan Xue, Zaozao Wang, Mei Liu, Hongxia Zhu, Ningzhi Xu, Ning Lu
Journal: Cancer Research (2012)

Abstract Objective: Human differentiated embryo chondrocyte expressed gene 1 (Dec1), also known as Bhlhb2/Stra13/Sharp-2, is a basic helix-loop-helix transcription factor that involves in cell proliferation, differentiation, apoptosis, and cellular senescence. In this study, the expression, function, diagnosis and prognostic impact of DEC1 in normal esophageal epithelia, esophageal squamous cell carcinoma (ESCC) and its precursor lesions (intraepithelial neoplasia) were investigated. Methods: ESCC combined with adjacent precursor tissues from 241 patients were collected to construct tissue microarray (TMA) blocks. DEC1 expression among normal epithelia, introepithelial neoplasia and ESCC was analyzed by immunohistochemistry (IHC), and the correlations between Dec1 and clinicopathological parameters were also analyzed statistically. In vitro study, DEC1 was transient transfected into ESCC cell line EC9706, and then cellular senescence was analyzed by senescence associated β-galactosidase (SA-α-Gal) activity. Fresh esophagectomy tissues from ESCC patients were embedded and fixed, and tissue sections were detected by immunohistochemistry of DEC1 and SA-α-Gal activity. Results: Compared with normal epithelia, DEC1 expression was significantly increased in intraepithelial neoplasia and DEC1 expression was significantly decreased in ESCC in comparison with intraepithelial neoplasia. DEC1 overexpression both induced cellular senescence in EC9706 cell line and correlated to more senescent cells in fresh tissue sections. Kaplan - Meier method analysis revealed that DEC1 expression levels were significantly correlated with the survival of ESCC patients after surgery. The expression levels of DEC1 were also correlated with the tumor embolus, depth of invasion of ESCC, lymph metastasis status and pTNMs. Conclusions: These results suggest that DEC1 overexpression is a protective mechanism by inducing cellular senescence in ESCC progression, and DEC1 is a potential prognostic marker of ESCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 732. doi:1538-7445.AM2012-732
Screening for Impaired Visual Acuity in Older Adults: U.S. Preventive Services Task Force Recommendation Statement
Journal: Annals of Internal Medicine (2009)

Description: Update of the 1996 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for visual impairment. Methods: The USPSTF reviewed evidence published since its last review on screening adults 65 years or older in the primary care setting for visual acuity impairment associated with uncorrected refractive errors, cataracts, and age-related macular degeneration. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for visual acuity for the improvement of outcomes in older adults. (I statement).
P230 Once-daily Tiotropium Respimat(R) Improves Lung Function In Patients With Severe Symptomatic Asthma Independent Of Leukotriene Modifier Use
Authors: R. Dahl, D. Doherty, J. Corren, J. Karpel, H. Kerstjens, M. Engel, P. Moroni-Zentgraf, H. Schmidt, S. Hashimoto
Journal: Thorax (2014)

<h3>Background</h3> Once-daily tiotropium Respimat<sup>®</sup>, a long-acting anticholinergic bronchodilator, has been shown in a Phase III programme to improve lung function and reduce severe exacerbation risk in patients with severe asthma who remain symptomatic despite using inhaled corticosteroids (ICS) + long-acting β<sub>2</sub>-agonist (LABA). Use of pre-trial leukotriene receptor antagonists (LTRAs) was not restricted; we analysed whether pre-screening LTRA use affected tiotropium Respimat<sup>®</sup> efficacy. <h3>Methods</h3> In two Phase III, replicate, randomised, double-blind, placebo-controlled, parallel-group trials (PrimoTinA-asthma<sup>®</sup>: NCT00772538, NCT00776984), symptomatic patients received high-dose ICS + LABA and once-daily tiotropium 5 µg or placebo (both delivered via the Respimat<sup>®</sup> SoftMist™ inhaler). LTRAs were permitted during run-in and treatment. Co-primary end points were peak and trough forced expiratory volume in 1 second (FEV<sub>1</sub>) responses (difference from baseline) at 24 weeks. Subgroups were defined by pre-screening LTRA use: 'Yes'/'No'. <h3>Results</h3> Of 912 randomised patients, 205 reported pre-screening LTRA use, 200 reported LTRA use during the treatment period and 187 had efficacy data at Week 24. Baseline characteristics were comparable between groups. Mean body mass index in LTRA 'Yes'/'No' groups was 27.8 kg/m<sup>2</sup> and 28.3 kg/m<sup>2</sup>, respectively. Mean% predicted FEV<sub>1</sub> at baseline was 56% in both groups. Lung function responses improved independent of LTRA use: peak FEV<sub>1</sub> was 99 ± 50 mL (p = 0.049) in the LTRA 'Yes' group and 113 ± 28 mL (p &lt; 0.001) in the LTRA 'No' group (peak FEV<sub>1</sub> improvements independent of concomitant LTRA use [interaction p value=0.6742]). Trough FEV<sub>1</sub> (difference from placebo) was 90 ± 46 mL (p = 0.052) in the LTRA 'Yes' group and 93 ± 25 mL (p &lt; 0.001) in the LTRA 'No' group (trough FEV<sub>1</sub> improvements independent of concomitant LTRA use [interaction p value = 0.5218]). <h3>Conclusion</h3> Once-daily tiotropium Respimat<sup>®</sup> added to ICS + LABA improves lung function in patients with severe symptomatic asthma, independent of initial LTRA use.
Achilles'-Tendon Xanthoma in Familial Hypercholesterolemia
Authors: H C van den Bosch, L D Vos
Journal: New England Journal of Medicine (1998)

Figure 1. A 22-year-old woman with a family history of hypercholesterolemia had had a soft-tissue swelling on the back of her left ankle for several years. Examination revealed a fusiform swelling of the Achilles' tendon. The serum cholesterol concentration was 352 mg per deciliter (9.1 mmol per liter), and triglyceride concentrations were normal. Physical examination revealed no other manifestations of a lipid disorder. Sagittal proton-weighted magnetic resonance imaging showed a homogeneously enlarged Achilles' tendon (arrow in Panel A) with increased signal intensity caused by xanthomatous material and parallel striation of low signal intensity caused by the collagen fibers of the . . .
COMPARISON OF CURRENT COSTS AND REIMBURSEMENT FOR TRANSCATHETER AND SURGICAL AORTIC VALVE REPLACEMENT
Authors: Mani Arsalan, Alessandro Ballard, Carl R. MacLachlan, Suzanne Arnold, David Cohen, Darren Mylotte, Joseph Cacchione, Nicolo Piazza, Giovanni Filardo, Michael Mack
Journal: Journal of the American College of Cardiology (2016)
The NICE Medical Technologies Evaluation Programme (MTEP): manufacturer submission challenges
Authors: Kirsty Sprange, Maxine Clift
Journal: Journal of the Royal Society of Medicine (2012)

The purpose of this report was to explore and describe the challenges that healthcare sector manufacturers face when producing a submission to the NICE Evaluation Pathway (EP) Programme for medical technologies. The EP Programme was developed to evaluate new and innovative medical technologies to inform adoption of efficient and cost effective devices and diagnostics in the NHS. The premise was to produce recommendations based on a similar process currently used for pharmaceutical products. A submission requires manufacturers to complete a data capture template collating high quality clinical and cost effectiveness evidence for their device. This includes indicating how the device integrates into current NHS clinical pathways and how it performs in relation to current best practice. The time scale for completion of a submission is an approximated 6 weeks. Particular consideration was given to small and medium enterprises (SMEs), and availability and access to resources and skills.

A consultation process was undertaken to ascertain the opinion of small, medium and large manufacturers in the healthcare sector who could potentially submit an application to the EP programme. The results of this process would highlight any real or perceived barriers identified by manufacturers that could prevent them from submitting to the new EP programme.

The EP programme was renamed after preparation of this report to the Medical Technologies Evaluation Programme (MTEP), and details are available here: http://www.nice.org.uk/mt.