tbuckley/cabot-search huggingface dataset:
P16.16 * INFLUENCE OF DETERMINATION OF PROGRESSION ON PATTERNS OF FLAIR FAILURE ANALYSIS IN PATIENTS WITH GRADE III ANAPLASTIC ASTROCYTOMA (AA) AND ASSOCIATION OF PATTERN OF FAILURE (POF) WITH SURVIVAL
Authors: T. Kazda, J. G. Hardie, D. H. Pafundi, D. H. Brinkmann, N. N. Laack
Journal: Neuro-Oncology (2014)

PURPOSE/OBJECTIVES: RANO criteria have recently been proposed as response guidelines for contrast-enhancing high grade gliomas, but the utility of these guidelines has not been established in AA. In this report we evaluated the utility of RANO criteria in determining progression and POF in AA and evaluated the association of POF with overall survival (OS). MATERIALS/METHODS: We performed a retrospective review of MR images for 21 consecutive patients with AA and radiologically-proven recurrence after irradiation at the Mayo Clinic (Rochester, MN). Three different criteria for identification of progression were used for each patient: 1) standard RANO-based criteria (RANO-C; most often met by development of new contrast enhancement or enlargement of contrast-enhancing lesion), 2) RANO criteria for progression based on significant FLAIR increase (RANO-F) and 3) clinical progression based on oncologist interpretation of imaging and clinical status usually resulting in change in treatment (Clinical). Time to progression was assessed among the three criteria using Friedman's test, and pairwise criteria using a sign test. After subtraction of tumor volume occurring on the best-response MR study, final structure was dosimetrically analyzed and different POF were characterized by the % volume encompassed within the 95% dose as follows: central (V95% ≥ 95%), in-field (80% ≤ V95% < 95%), marginal (20% ≤ V95% < 80%), or distant (V95% < 20%). RESULTS: Time to progression based on RANO criteria preceeded the clinical diagnosis of progression by a median of 3.13 months (9.2 vs 12.6 mo p < 0.0001, Sign test). New or progressive contrast enhancement (RANO-C) was almost entirely central or in-field (95% and 5%, respectively). POF of FLAIR component differed based on timepoint used to determine progression. FLAIR POF was significantly more often marginal or distant when progression was defined clinically compared to either RANO-C or RANO-F criteria (p = .03 and .007 respectively). POF for FLAIR abnormality at the time of RANO-C was 33% central, 24% in-field and 43% marginal; at RANO-F was 47%, 16% and 37% respectively, and at the time of Clinical recurrence were more often peripheral with 19% central, 24% in-field, 52% marginal and 1 patient (5%) distant. No association with POF and OS was seen when evaluated at the time of RANO defined progression. Central POF at Clinical determination of progression was associated with poorer OS (9.8 vs 29.7 months, p = 0.017). CONCLUSION: POF analysis in AA is dependent on method of progression determination. Time to progression based on RANO criteria generally preceeded clinician impression. POF at the time of RANO determination of progression was not associated with survival. Central recurrence as evaluated at the time of clinical progression is strongly associated with poorer OS.
P4-18-01: Prognostic Role of Tumor and Stromal p16/INK4A in Ductal Carcinoma In Situ (DCIS).
Authors: SP Linke, TM Bremer, F Wärnberg, W Zhou, L Goldstein, K Jirström, R-M Amini
Journal: Cancer Research (2011)

Abstract Background DCIS is a pre-invasive breast disease diagnosed in ∼50,000 women/year in the US. The standard treatment recommendation is for mastectomy or breast-conserving surgery plus radiotherapy (BCS+RT). However, only ∼10% of BCS patients avoid recurrence due to RT, and RT provides little or no survival benefit. Thus, it is important to stratify patients by risk to help tailor treatment to maximize benefit and minimize unnecessary adverse effects and costs. Material and Methods: Tissue microarrays that included tumor cores from all women diagnosed with pure DCIS between 1986 and 2004 in Uppland and Västmanland, Sweden (n=458) were stained and scored for p16/INK4A (clone E6H4) using immunohistochemistry (IHC). Semi-quantitative manual scoring was done separately in the tumor epithelial cells and peri-tumoral carcinoma-associated fibroblasts (CAFs). Based on previous reports, thresholds to define low and high p16 levels were set at 25% and 5% positive staining, respectively, for the tumor and stromal components. HER2 IHC scoring was reported previously. Clinicopathologic characteristics of the set of patients for which complete marker data was obtained (n=176) were not statistically different than the full set of patients. For survival analysis, local ipsilateral DCIS and invasive recurrences, as well as lymph node and distant metastases, were included as events (patients were censored if they had contralateral breast or other cancers as the first event). Results: Patients were stratified into low and high risk groups using a multivariate model incorporating tumor p16, stromal p16, HER2, and margin status. Patients treated with BCS only (n=67) had a baseline 10-year recurrence rate of 31%. The model identified high and low risk groups with 10-year recurrence rates of 38% and 7%, respectively (hazard ratio=7.1, p=0.009). Similar results were achieved when BCS only and BCS+RT patients were combined (n=130). Interestingly, all six recurrence events in the set of patients who received full mastectomies (n=43) were in the model high risk group. Discussion: Previous studies have shown mixed results when p16 was used as a single marker. Our results suggest a prognostic interaction between tumor and stromal p16, as well as HER2, that will form the basis of a more comprehensive multi-marker IHC-based prognostic panel to assess risk of recurrence in DCIS patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-18-01.
Treatment of primary CLL cells with bezafibrate and medroxyprogesterone acetate induces apoptosis and represses the pro-proliferative signal of CD40-ligand, in part through increased 15dΔ12,14,PGJ2
Authors: R E Hayden, G Pratt, N J Davies, F L Khanim, J Birtwistle, J Delgado, C Pearce, T Sant, M T Drayson, C M Bunce
Journal: Leukemia (2008)
CARACTERISTICAS Y ESTANCIA MEDIA EN PACIENTES MAYORES DE 80 AÑOS QUE PRECISAN UNA CPRE
Authors: J Espinel, R Diez, A Domínguez, G Rascarachi, S Vivas, F Muñoz
Journal: Endoscopy (2010)

Objetivo: Evaluar las características (antecedentes, diagnóstico obtenido, terapéutica realizada, complicaciones) y estancia media de los pacientes mayores de 80 años que se someten a una CPRE.
A New Vaccine to Prevent Herpes Zoster
Authors: Jeffrey I. Cohen
Journal: New England Journal of Medicine (2015)

Among persons who live until the age of 85 years, herpes zoster will develop in approximately half, with an incidence that seems to be increasing. Although the disease may be mild in healthy young adults, persons over the age of 50 years and those who are immunocompromised are more likely to have complications that include herpes zoster ophthalmicus and postherpetic neuralgia.The live attenuated herpes zoster vaccine that is licensed in the United States reduces the incidence of herpes zoster by 70% among persons between the ages of 50 and 59 years, by 64% among those between the ages of . . .
Clinical Experiences with 2, 6-Dimethoxyphenyl Penicillin Monohydrate in Staphylococcal Infections
Authors: Alexander M. Rutenburg, Harold L. Greenberg, Fritz B. Schweinburg
Journal: New England Journal of Medicine (1960)

2,6-DIMETHOXYPHENYL penicillin monohydrate is a new synthetic penicillin said to be effective in vitro against a variety of gram-positive bacteria, including hemolytic staphylococci resistant to penicillin G.1 The present report deals with the in vitro antimicrobial activity of dimethoxyphenyl penicillin in comparison to penicillin G against 100 isolates of staphylococci from clinical sources and its efficacy in the treatment of 41 patients with surgical infections due largely to staphylococci. This series includes 31 patients who had failed to respond to other antibiotics and 10 others treated only with dimethoxyphenyl penicillin.In Vitro StudiesOne hundred clinical isolates¶ of staphylococci, most . . .
AB0917 Clinical, biological and radiological particularities of destructive hip arthritis in ankylosing spondylitis
Authors: W. Hamdi, M.M. Ghannouchi, Z. Alaya, M. Bouaziz, F.M. Ladeb, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The hip involvement in patients with ankylosing spondylitis (AS) has been recognized as a common and disabling problem. Many radiological pattern of hip arthritis were recognized and seems to have different clinical profile. <h3>Objectives</h3> to compare the destructive hip arthritis to other radiological pattern in patients with AS. <h3>Methods</h3> One hundred patients with AS, diagnosed according to the modified New York criteria for AS, and with hip involvement were recruited. Clinical, biological and radiological examinations for AS and for the hip involvement were performed and disease-specific instruments (BASFI, BASDAI, BASG-s, BASMI, BASRI, mSASSS) were assessed. Chi2 test was used to compare qualitative variables and ANOVA for quantitative variables. <h3>Results</h3> Eighty-one males and 19 females with AS were included in this study. Their mean age was 36.3 years ± 12.3. The mean disease duration was 12.3 years ± 0.9. Sixty-two patients were HLA-B27 positive. The hip involvement was bilateral in 76 cases (176 hips), inaugural in 46 cases and for the others, the mean disease duration at hip arthritis onset was 5.6 years. The destructive hip arthritis was found in 65% of cases and was associated among hip arthritis parameters to Lequesne index, reduced maximum distance walked, lameness, limitations in hip rotation and total hip replacement requirement. Among AS parameters destructive arthritis was associated to high score of BASRI, high level of ESR and presence of B27 antigen. <h3>Conclusions</h3> The destructive hip arthritis seems to be the most frequent radiological pattern and associated to the presence of HLA B27 antigen and to a worse prognosis. <h3>Disclosure of Interest</h3> None Declared
Introduction: Biological Markers of Male Reproductive Toxicology
Authors: Larry L. Ewing, Donald R. Mattison
Journal: Environmental Health Perspectives (1987)

Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals (1-6).
Validation of a genomic classifier (ColoPrint) for predicting outcome in the T3-MSS subgroup of stage II colon cancer patients.
Authors: Ramon Salazar, Josep Tabernero, Victor Moreno, Ulrich Nitsche, Thomas Bachleitner-Hofmann, Giovanni Lanza, Lisette Stork, Paul Roepman, Iris Simon, Robert Rosenberg
Journal: Journal of Clinical Oncology (2012)

3510 Background: Adjuvant therapy for stage II patients is recommended for patients with high risk features, especially with T4 tumors. Adjuvant therapy is not indicated for patients with MSI-H status who are considered of being at low risk of disease relapse. However, this leaves the majority of patients with an undetermined risk. ColoPrint is an 18-gene expression classifier that identifies early-stage colon cancer patients at higher risk of disease relapse. Methods: ColoPrint was developed using whole genome expression data and was validated in public datasets (n=322) and independent patient cohorts from 5 European hospitals. Tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 70 months) for patients were available and the ColoPrint index was determined using validated diagnostic arrays. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) and the subset of patients who were T3/ MSS (n=227). Results: In the analysis of all stage II patients, ColoPrint classified two-third of stage II patients as being at lower risk. The 3-year Relapse-Free-Survial (RFS) RFS was 91% for Low Risk and 74% for patients at higher risk with a HR of 2.9 (p=0.001). Clinicopathological parameters from the ASCO recommendations (T4, perforation, &lt;12 LN assessed, and/ or high grade) or NCCN guidelines (ASCO factors plus angio-lymphatic invasion) did not predict a differential outcome for high risk patients (p&lt; 0.20). In the subgroup of patients with T3 and MSS phenotype, ColoPrint classified 61% of patients at lower risk with a 3-year RFS of 91% (86-96%) and 39% of patients at higher risk with a 3-year RFS of 73% (63-83%) (p=0.002). No clinical parameter was significantly prognostic in this subgroup. Conclusions: ColoPrint combined with established clinicopathological factors and MSI, significantly improves prognostic accuracy, thereby facilitating the identification of patients at higher risk who might be considered for additional treatment.
Abstract 765: Drug discovery for targeting the tumor microenvironment from propolis
Authors: Hideko K. Nagasawa, Hisanori Hattori, Kosuke Narise, Tatsuya Watarai, Satoshi Ueda, Kensuke Okuda
Journal: Cancer Research (2010)

Abstract The tumor microenvironment, characterized by regions of hypoxia, low nutrition, and acidosis due to incomplete blood vessel networks, has been recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also malignant progression and metastasis. However, exploiting such a cumbersome tumor microenvironment for cancer treatment could provide tumor-specific therapeutic approaches. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment in which HIF-1 mediated gene regulation being essential for angiogenesis and tumor development. This has led to the current extensive interest in the drug discovery for tumor microenvironment including tumor specific potential molecular targets for cancer therapeutics. Propolis has pleiotropic effects and contains a variety of bioactive polyphenolic compounds. Some flavonoids of them have been reported to inhibit HIF-1α. We therefore evaluated the effects of composition of Brazilian propolis on cellular responses to hypoxia or nutrition deprivation stress for the development of novel anti-cancer drug targeting the tumor microenvironment. Materials and Method: The ethanol extract of Brazilian propolis was subjected to a series of chromatographic separations to examine HIF-1 inhibition and cytotoxicity under hypoxic and/or glucose deprived condition. The HIF-1α trans-activation effect was evaluated by HIF-1 reporter assay using stable cell lines expressing p2.1. The effect on unfolded protein response (UPR) activation in tumor cell induced by glucose deprivation or 2-deoxyglucose was also examined by GRP78 promoter reporter assay. We performed Immunoblot analysis of the HIF-1α and UPR target genes. The effects on HIF-1α dependent gene expression were investigated by RT-PCR using HCT116 cells. Result: The propolis whole extract increased HRE-dependent luciferase activity in a dose-dependent manner. From a series of chromatographic separations, we obtained fractions 3, 5 and 8 that inhibited HIF-1-dependent induction of luciferase, while fractions 6 and 10-13 increased the luciferase activity. Cinnamic acid derivative, GPU-215 was isolated from Fr.6 reduced HIF1 transactivation activity, expression of HIF-1α protein and GLUT1 mRNA under hypoxia, while flavonoid, GPU-216 from Fr.8 increased HIF-1α transactivation activity and UPR activation. Conclusion: We discovered promising compounds from Brazilian propolis for novel anti-cancer drug targeting tumor microenvironment. GPU-215 has inhibitory effect on HIF-1α expression and function, while GPU-216 increased HIF-1α transactivation and UPR activation. 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 765.
Abstract 2954: Overexpression of specific genes in surgical margins of head and neck squamous cell carcinoma patients may predict a significantly increased risk of recurrence
Authors: Ana Carolina de Carvalho, André L. Carvalho, Fernando A. Soares, Luiz Paulo Kowalski, Danielle C C Maia, Marianna M. Rettori, André L. Vettore
Journal: Cancer Research (2010)

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is a high incidence and mortality disease. Despite significant improvements in therapeutic strategies, the overall survival rate in 5 years is around 50%. The presence of microscopic tumor in surgical margins is associated with treatment failure, locoregional recurrence and reduction of overall survival. For this reason, it is vital to ensure tumor-free surgical margins in these patients. Commonly, the extension of surgical resection is determined during the surgery through a low sensitivity histological exam of frozen tissue stained with Hematoxylin and Eosin. Since genetic alterations precede histological alterations, molecular markers may be useful to identify cells that have already started malignant transformation without having developed a histological phenotype that could be detected through conventional histopathological techniques. Also, novel molecular techniques make possible to obtain molecular data of surgical margins in a period of time compatible with the surgery, helping the surgeon in the resection of positive molecular margins in the same surgery and thereby reducing the risk of local recurrence. This study aimed to determine the gene expression pattern of specific markers in HNSCC surgical margins and verify the utility of these markers in detecting the presence of tumor cells in these tissues and predict tumor recurrence. Nine selected genes were evaluated and a panel of 5 genes showed a high specificity and good sensibility. Overexpression of at least one of these genes was found in 50% (23/46) of histologically free surgical margins analyzed and was associated with local recurrence. Patients with positive molecular margins were 7.3-fold more likely to have local recurrence. These preliminary results suggest that the approach used in this analysis is more sensible than traditional histopathological exams and could be useful for the intraoperative diagnosis of the presence of tumor cells in HNSCC surgical margins and as an informative tool to identify and monitor subsets of HNSCC patients with an increased risk of recurrence and consequently reduced survival. 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 2954.
Coronary Collateral Growth Induced by Physical Exercise
Authors: Sven Möbius-Winkler, Madlen Uhlemann, Volker Adams, Marcus Sandri, Sandra Erbs, Karsten Lenk, Norman Mangner, Ulrike Mueller, Jennifer Adam, Martin Grunze, Susanne Brunner, Thomas Hilberg, Meinhard Mende, Axel P. Linke, Gerhard Schuler
Journal: Circulation (2016)

A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear.This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ≤0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, Vo2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B.A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.
SP0061 Rheumatoid Arthritis Remission Criteria in Practice and Studies
Authors: C. F. Allaart
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> In recent years it has been shown that remission may be a realistic goal to aim for when treating rheumatoid arthritis. How to define remission has been a matter of debate, often initiated by the observation that a certain definition allows for the presence of some symptoms or signs that would indicate residual disease activity, or by the expectation that with time, residual disease activity would become apparent. More stringent definitions, with longer follow up requirements, are then proposed. When aiming to be a gold standard of absent disease, to test new methods of measuring disease activity, remission definitions would be have to be so stringent as to denote 'cure', if this exists in RA. In daily practice and in most dictionaries remission, coming from Latin <i>remittere</i>, to send back, is called a situation where in a chronic disease (remission does not mean cured), by active intervention (there is no 'spontaneous remission', only regression or resolution) there are no longer symptoms. This means that patient and physician need only to agree that the patient is free of clinical manifestations of the disease, and that laboratory signs, lingering evidence of chronicity, persistence of risk factors or abnormal cells or cell activities, need not be absent. Used in daily practice, time efficient methods are needed, that provide sufficient security to allow treatment decisions based on the result. In RA, where previous disease activity may have caused damage, this may result in symptoms which are not clinical manifestations of disease activity. Such symptoms do not preclude that remission may be achieved. Composite scores which include signs of inflammation may help to assess if there is 'remission with symptoms'. Various composite scores come with their own definition of remission, and these may not all identify the same patients. In research papers on cohorts and observational studies, it is sufficient to use clinical remission criteria. In order to be able to compare outcomes between studies, it would be helpful to report data using the same remission definition in each study. Whether one definition is better than the others and if so, why, will be discussed. <h3>Disclosure of Interest</h3> None Declared