tbuckley/cabot-search huggingface dataset:
Combined transbronchial needle aspiration and positron emission tomography for mediastinal staging of NSCLC
Authors: M. Bernasconi, P. N. Chhajed, F. Gambazzi, L. Bubendorf, H. Rasch, S. Kneifel, M. Tamm
Journal: European Respiratory Journal (2006)

There are no data available combining transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and positron emission tomography (PET) in the staging of nonsmall cell lung cancer (NSCLC). The aim of the current study was to determine if these two methods can enhance the negative predictive value of the individual modality alone, for a specific lymph node station, and if this integrated approach can reduce the number of mediastinoscopies. A total of 113 patients with enlarged mediastinal lymph nodes (> or = 1 cm), who underwent both TBNA and PET scanning, were included. In 51 patients, histopathology, confirmed by surgical lymph node dissection, was compared with PET results and TBNA. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect malignant lymphadenopathy was 68 (13/19), 89 (119/134), 46 (13/28), 95 (119/125) and 86% (132/152) for PET, respectively; 54% (6/11), 100 (53/53), 100 (6/6), 91 (53/58) and 92% (59/64), respectively for TBNA; and 100 (11/11), 94 (50/53), 79 (11/14), 100 (50/50) and 95 (61/64) for combined TBNA and PET, respectively. Combination of transbronchial needle aspiration and positron emission tomography has the potential to allow adequate mediastinal staging of nonsmall cell lung cancer with enlarged lymph nodes in most patients without the need for mediastinoscopy.
PROLONGED WATER DEPRIVATION IN THE DOG 1
Authors: J. Russell Elkinton, Max Taffel
Journal: Journal of Clinical Investigation (1942)

Evidence of intracellular as well as of extra- cellular water depletion was obtained during pe- riods of water deprivation in some experiments on pyloric obstruction in dogs.The object of this control study was to observe the exchanges of body water and salts as conditioned by the strict deprivation of water.
Coexpression of neuronatin splice forms promotes medulloblastoma growth
Authors: I-Mei Siu, Renyuan Bai, Gary L. Gallia, Jennifer B. Edwards, Betty M. Tyler, Charles G. Eberhart, Gregory J. Riggins
Journal: Neuro-Oncology (2008)

Medulloblastoma (MB) is the most common pediatric brain cancer. Several important developmental pathways have been implicated in MB formation, but fewer therapeutic targets have been identified. To locate frequently overexpressed genes, we performed a comprehensive gene expression survey of MB. Our comparison of 20 primary tumors to normal cerebellum identified neuronatin (NNAT) as the most frequently overexpressed gene in our analysis. NNAT is a neural-specific developmental gene with α and β splice forms. Functional evaluation revealed that RNA interference knockdown of NNAT causes a significant decrease in proliferation. Conversely, coexpression of both splice forms in NNAT-negative MB cell lines increased proliferation, caused a significant shift from G1 to G2/M, and increased soft agar colony formation and size. When expressed individually, each NNAT splice form had much less effect on these in vitro oncogenic predictors. In an in vivo model, the coexpression of both splice forms conferred the ability of xenograft formation to human MB cells that do not normally form xenografts, whereas a control gene had no effect. Our findings suggest that the frequently observed overexpression of both NNAT splice forms in MB enhances growth in this cancer.
Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients
Authors: Alexander J. Thompson, Paul J. Clark, Abanish Singh, Dongliang Ge, Jacques Fellay, Mingfu Zhu, Qianqian Zhu, Thomas J. Urban, Keyur Patel, Hans L. Tillmann, Susanna Naggie, Nezam H. Afdhal, Ira M. Jacobson, Rafael Esteban, Fred Poordad, Eric J. Lawitz, Jonathan McCone, Mitchell L. Shiffman, Greg W. Galler, John W. King, Paul Y. Kwo, Kevin V. Shianna, Stephanie Noviello, Lisa D. Pedicone, Clifford A. Brass, Janice K. Albrecht, Mark S. Sulkowski, David B. Goldstein, John G. McHutchison, Andrew J. Muir
Journal: Journal of Hepatology (2011)
The influence of central review on outcome associations in childhood malignant gliomas: Results from the CCG-945 experience
Authors: Ian F. Pollack, James M. Boyett, Allan J. Yates, Peter C. Burger, Floyd H. Gilles, Richard L. Davis, Jonathan L. Finlay
Journal: Neuro-Oncology (2003)

To examine the influence of the pathology review mechanism on the results of analyses of therapeutic efficacy and biological prognostic correlates for pediatric high-grade gliomas, we evaluated the effects of using single-expert review or consensus review, as alternatives to institutional classification, in determining outcome results of a large randomized trial. The study group was the randomized cohort of Children's Cancer Group study 945, which compared efficacy of 2 chemotherapy regimens adjuvant to surgery and radiation. Trial eligibility required institutional histopathologic diagnosis of high-grade glioma. Sections of study tumors also were centrally reviewed, initially by a study review neuropathologist and subsequently by 5 neuropathologists, including the review pathologist. Reviews were independent, and reviewers were masked to clinical factors and outcomes, and consensus diagnoses of the panel were then established. Among 172 eligible patients, 42 tumors were classified as discordant on single-expert review and 51 on consensus review. Progression-free survival probabilities calculated for patients with tumors classified as high-grade gliomas by either single-expert or consensus review were inferior to those for the overall, institutionally diagnosed cohort. However, conclusions of the study regarding relative efficacy of treatment and clinical and molecular outcome correlates were unaffected by diagnosis method. Resection extent, proliferation index, and p53 expression were associated strongly with outcome, regardless of diagnosis method. However, comparisons between arms in which inclusion was determined by different review criteria for each arm caused spurious conclusions about efficacy differences between treatments. We conclude that the pathology review mechanism had little effect on within-trial comparisons of therapeutic effects or prognostic correlates in this randomized study, but strongly influenced survival distributions that were calculated for each treatment arm. These results support the implementation of expedited central review in therapeutic studies involving childhood malignant gliomas as a way to prospectively identify and exclude cases with discordant diagnoses and indicate the need for additional measures, such as molecular assessments, to increase the reproducibility of neuro pathologic classification for these tumors.
Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site
Authors: Kurtis Eisermann, Carly J Broderick, Anton Bazarov, Mustafa M Moazam, Gail C Fraizer
Journal: Molecular Cancer (2013)

Abstract Background Vascular Endothelial Growth Factor (VEGF) is regulated by a number of different factors, but the mechanism(s) behind androgen-mediated regulation of VEGF in prostate cancer are poorly understood. Results Three novel androgen receptor (AR) binding sites were discovered in the VEGF promoter and in vivo binding of AR to these sites was demonstrated by chromatin immunoprecipitation. Mutation of these sites attenuated activation of the VEGF promoter by the androgen analog, R1881 in prostate cancer cells. The transcription factors AR and Sp1 were shown to form a nuclear complex and both bound the VEGF core promoter in chromatin of hormone treated CWR22Rv1 prostate cancer cells. The importance of the Sp1 binding site in hormone mediated activation of VEGF expression was demonstrated by site directed mutagenesis. Mutation of a critical Sp1 binding site (Sp1.4) in the VEGF core promoter region prevented activation by androgen. Similarly, suppression of Sp1 binding by Mithramycin A treatment significantly reduced VEGF expression. Conclusions Our mechanistic study of androgen mediated induction of VEGF expression in prostate cancer cells revealed for the first time that this induction is mediated through the core promoter region and is dependent upon a critical Sp1 binding site. The importance of Sp1 binding suggests that therapy targeting the AR-Sp1 complex may dampen VEGF induced angiogenesis and, thereby, block prostate cancer progression, helping to maintain the indolent form of prostate cancer.
Metabolism and Distribution of Intravenously Administered d-Aldosterone-l,2-H <sup>3</sup> in the Arteries, Kidneys, and Heart of Dog
Authors: WILLIAM HOLLANDER, DIETER M. KRAMSCH, ARAM V. CHOBANIAN, JAMES C. MELBY
Journal: Circulation Research (1966)

The initial disappearance of intravenously administered H 3 -d-aldosterone from the plasma was associated with a rapid uptake of the labeled aldosterone in the tissues. The subsequent, slower fall off of plasma aldosterone radioactivity appeared to parallel the biological decay of H 3 -aldosterone in the tissues. H 3 -d-aldosterone attained a maximal level in the kidney, liver, heart, and aorta of dog in five to 15 minutes after the aldosterone injection. During and after the time of peak tissue radioactivity, H 3 -aldosterone radioactivity was higher in the kidney, liver, heart, and thoracic aorta than in the plasma. No consistent relationship was observed between the H 3 -aldosterone uptake and the salt, water, and acid mucopolysaccharide content of different portions of the aorta. Subcellular fractionation of the tissues indicated that most of the H 3 -aldosterone taken up by the tissues was present in the supernatant fraction and not bound to subcellular particles. Radioautography revealed a high concentration of H 3 -aldosterone along the cell walls of the convoluted tubular cells and along the walls of the glomerular capillaries, arterioles, and Bowman's capsule. In the heart H 3 -aldosterone localized along the cell walls of the heart muscle cells, whereas in the aorta the hormone appeared to accumulate over the cytoplasm of the smooth muscle cells. The uptake and distribution of H 3 -aldosterone in the tissues were not altered by pretreatment with the aldosterone antagonist, spironolactone.
Duration but not Intensity of Alcohol and Tobacco Exposure Predicts <i>p16INK4A</i> Homozygous Deletion in Head and Neck Squamous Cell Carcinoma
Authors: Kim S. Kraunz, Michael D. McClean, Heather H. Nelson, Edward Peters, Henry Calderon, Karl T. Kelsey
Journal: Cancer Research (2006)

Abstract In tobacco-associated solid tumors, evidence suggests that the pattern of carcinogen exposure is related to the nature of somatic gene inactivation within crucial pathways, including the retinoblastoma (Rb) pathway. One somatic event in this pathway, homozygous deletion of the p16INK4A gene, is commonly observed in head and neck squamous cell carcinoma (HNSCC). Alcohol and tobacco are both well-established risk factors for HNSCC but there has been little characterization of the relationship of exposure to these carcinogens and inactivation of the p16INK4A gene. Hypothesizing that p16INK4A homozygous deletion is associated with tobacco and alcohol exposure, we investigated 330 consecutive HNSCC tumors. The odds ratio (OR) for p16INK4A homozygous deletion among alcohol consumers in the upper tertile (&amp;gt;43 years used) was 5.2 [95% confidence interval (95% CI), 2.1-12.8] as compared with those with ≤43 years of alcohol consumption. Intensity of alcohol exposure, measured as average alcoholic drinks per week, was not associated with gene deletion. When we examined the distribution of duration of tobacco use, the OR for p16INK4A homozygous deletion was 1.3 (95% CI, 0.5-3.0) and 1.9 (95% CI, 0.9-4.0) for 29 to 39 years and &amp;gt;39 years of tobacco smoking, respectively, as compared with those that smoked ≤28 years. As in the case of alcohol use, intensity of tobacco exposure (measured as packs per day) was not associated with gene deletion. Hence, the duration of alcohol use and duration of smoking, but not intensity of either, significantly predicted p16INK4A homozygous deletion in HNSCC. (Cancer Res 2006; 66(8): 4512-5)
Induction of the immune response to periodontopathic bacteria and its role in the pathogenesis of periodontitis
Authors: ISAO ISHIKAWA, KEISUKE NAKASHIMA, TAKEYOSHI KOSEKI, TOSHIYUKI NAGASAWA, HISASHI WATANABE, SHINICHI ARAKAWA, HIROSHI NITTA, TATSUJI NISHIHARA
Journal: Periodontology 2000 (1997)
Novel Targeted Agents and the Need to Refine Clinical End Points in Chronic Lymphocytic Leukemia
Authors: Bruce D. Cheson, John C. Byrd, Kanti R. Rai, Neil E. Kay, Susan M. O'Brien, Ian W. Flinn, Adrian Wiestner, Thomas J. Kipps
Journal: Journal of Clinical Oncology (2012)

Standardized criteria for response to therapy in patients with chronic lymphocytic leukemia (CLL), lymphoma, and other malignancies allow for comparisons of outcome between clinical trials and have facilitated regulatory agency approval of novel active agents for use in current standard therapy. In 1988, the National Cancer Institute (NCI) Working Group published the first widely accepted criteria for CLL,1 which were revised in 1996.2 Such recommendations were developed in the context of currently available cytotoxic therapies. Later, in 2008, the International Workshop on CLL published criteria that incorporated much of the 1996 guidelines but also included guidance on how to assess minimal residual disease after therapy.3 These published guidelines defined therapy outcome as either complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), based on surrogate markers of tumor burden, such as blood lymphocyte count, lymph node size, or spleen size, and indicators of improved marrow function or clearance of leukemia cells from the marrow, as assessed by serial blood counts and/or marrow aspirate and biopsy. In general, these response criteria (CR, PR, SD, and PD) in therapeutic trials have correlated with the length of progression-free survival (PFS) and occasionally overall survival after treatment. Because assessment of response using these criteria can often be made years before survival data are available, response criteria have served as useful surrogate markers for assessing the clinical benefit of therapy, thereby accelerating the pace of approval of novel agents for use in the treatment of patients.
Angiotensinogen Delays Angiogenesis and Tumor Growth of Hepatocarcinoma in Transgenic Mice
Authors: François Vincent, Philippe Bonnin, Maud Clemessy, Jean-Olivier Contrerès, Noël Lamandé, Jean-Marie Gasc, José Vilar, Patricia Hainaud, Gérard Tobelem, Pierre Corvol, Evelyne Dupuy
Journal: Cancer Research (2009)

Angiotensinogen, a member of the serpin family, is involved in the suppression of tumor growth and metastasis. To investigate whether human angiotensinogen protects against tumor progression in vivo, we established an original bitransgenic model in which transgenic mice expressing human angiotensinogen (Hu-AGT-TG mice) were crossed with a transgenic mouse model of hepatocellular carcinoma (HCC-TG mice). Bitransgenic mice overexpressing human angiotensinogen (HCC/Hu-AGT-TG) had a significantly longer survival time than the HCC-TG mice and a reduction of both tumor growth and blood flow velocities in the liver. This antitumor effect of angiotensinogen is related to a reduced angiogenesis, impaired expression of endothelial arterial markers (active Notch4, Delta-like 4 ligand, and ephrin B2) with a decrease of arterial vessel density in HCC/Hu-AGT-TG mice liver. Overexpression of human angiotensinogen decreases angiogenesis, and prevents tumor sinusoids from remodeling and arterialization, thus delaying tumor progression in vivo.
An Accurate Risk Score Based on Anthropometric, Dietary, and Lifestyle Factors to Predict the Development of Type 2 Diabetes
Authors: Matthias B. Schulze, Kurt Hoffmann, Heiner Boeing, Jakob Linseisen, Sabine Rohrmann, Matthias Möhlig, Andreas F.H. Pfeiffer, Joachim Spranger, Claus Thamer, Hans-Ulrich Häring, Andreas Fritsche, Hans-Georg Joost
Journal: Diabetes Care (2007)

We aimed to develop a precise risk score for the screening of large populations for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study populations.A prospective cohort study (European Prospective Investigation into Cancer and Nutrition [EPIC]-Potsdam study) of 9,729 men and 15,438 women aged 35-65 years was used to derive a risk score predicting incident type 2 diabetes. Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score. Data from the EPIC-Heidelberg, the Tübingen Family Study for Type 2 Diabetes (TUF), and the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study were used to validate this score.Information on age, waist circumference, height, history of hypertension, physical activity, smoking, and consumption of red meat, whole-grain bread, coffee, and alcohol formed the German Diabetes Risk Score (mean 446 points [range 118-983]). The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3% for 300 to 23.2% for 750 score points. The area under the receiver-operator characteristic (ROC) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies. Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were -0.56 in the TUF and -0.45 in the MeSyBePo studies. ROC values for undiagnosed diabetes were 0.83 in the TUF and 0.75 in the MeSyBePo studies.The German Diabetes Risk Score (available at www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes.
Does exposure to landfill waste harm the fetus?
Authors: R McNamee
Journal: BMJ (2001)

Papers p 363 

In this issue Elliott and colleagues report on the risks to fetuses associated with residence near landfill sites: they compared pregnancy outcomes among British women living within 2 km of any of 9565 landfill sites operational between 1982 and 1997 with outcomes among those who lived at least 2 km away from all known sites (the reference area).1 They found excess risks for some adverse pregnancy outcomes, a finding consistent with previous literature, but a clear pattern of excess did not emerge and the excesses were small enough (generally less than 10%) that they could be due to study bias, a problem that is difficult to rule out in this type of study. Therefore, the question whether these results represent a causal connection between residential exposures to landfill and adverse outcomes is unresolved.

The authors found that 80% of the British population lives within 2 km of a current or closed landfill site. This remarkable finding has several implications. Firstly, it suggests that even small excess risks near landfill sites would be important in public health terms. Secondly, it raises the question of whether the reference population is unusual, and thus …
Mechanism of Radiosensitization by the Chk1/2 Inhibitor AZD7762 Involves Abrogation of the G2 Checkpoint and Inhibition of Homologous Recombinational DNA Repair
Authors: Meredith A. Morgan, Leslie A. Parsels, Lili Zhao, Joshua D. Parsels, Mary A. Davis, Maria C. Hassan, Sankari Arumugarajah, Linda Hylander-Gans, Deborah Morosini, Diane M. Simeone, Christine E. Canman, Daniel P. Normolle, Sonya D. Zabludoff, Jonathan Maybaum, Theodore S. Lawrence
Journal: Cancer Research (2010)

The median survival for patients with locally advanced pancreatic cancer treated with gemcitabine and radiation is approximately 1 year. To develop improved treatment, we have combined a Chk1/2-targeted agent, AZD7762, currently in phase I clinical trials, with gemcitabine and ionizing radiation in preclinical pancreatic tumor models. We found that in vitro AZD7762 alone or in combination with gemcitabine significantly sensitized MiaPaCa-2 cells to radiation. AZD7762 inhibited Chk1 autophosphorylation (S296 Chk1), stabilized Cdc25A, and increased ATR/ATM-mediated Chk1 phosphorylation (S345 Chk1). Radiosensitization by AZD7762 was associated with abrogation of the G(2) checkpoint as well as with inhibition of Rad51 focus formation, inhibition of homologous recombination repair, and persistent gamma-H2AX expression. AZD7762 was also a radiation sensitizer in multiple tumor xenograft models. In both MiaPaCa-2- and patient-derived xenografts, AZD7762 significantly prolonged the median time required for tumor volume doubling in response to gemcitabine and radiation. Together, our findings suggest that G(2) checkpoint abrogation and homologous recombination repair inhibition both contribute to sensitization by Chk1 inhibition. Furthermore, they support the clinical use of AZD7762 in combination with gemcitabine and radiation for patients with locally advanced pancreatic cancer.
Refractory periods of the accessory pathway in the Wolff-Parkinson-White syndrome.
Authors: A M Tonkin, H C Miller, R H Svenson, A G Wallace, J J Gallagher
Journal: Circulation (1975)

Antegrade (AERPAP) and retrograde (RERPAP) effective refractory periods of the accessory pathway were measured at multiple cycle lengths in 47 patients with the Wolff-Parkinson-White syndrome. In 20 patients the effect of changing cycle length on AERPAP could be determined. In 12 patients Aerpap decreased by 10-45 msec, in six it increased by 10-35 msec, and in two it was unchanged. In 13 of 15 patients in whom the effect of decreasing cycle length on RERPAP could be assessed, RERPAP decreased by 10-60 msec. In eight patients, the shortest AERPAP correlated well (r equals 0.83) with the shortest R-R interval of consecutive pre-excited beats in atrial fibrillation. However, predominantly normal conduction was observed in six of 28 patients with atrial fibrillation, probably because of concealment in the bypass. Therefore, induction of atrial fibrillation during electrophysiological evaluation may privide additional information. The RERPAP at the cycle length of the arrhythmia was shorter than the cycle length of reciprocating tachycardia in all but one of 21 patients. At the same or comparable cycle lengths, AERPAP was usually greater than RERPAP.
A Personal View of Pharmacology
Authors: James Black
Journal: The Annual Review of Pharmacology and Toxicology (1996)

This essay is an account of the author’s experience in trying to interpret the action of drugs as seen in in vitro bioassays. The central theme is how the development of simple mathematical models has assisted in the interpretation of drug actions. Starting from encounters with partial agonists, the essay describes the development of an operational model of agonist activity, the significance of receptor distribution, the analysis of indirect competitive antagonism and various two-receptor systems, followed by examples of pharmacological resultant activity. Analyses of tissue and species variations are described. The essay ends with an assessment of the future of bioassay in pharmacology
Serum Sertraline and <b><i>N</i></b>-Desmethylsertraline Levels in Breast-Feeding Mother-Infant Pairs
Authors: Katherine L. Wisner, James M. Perel, Jeffrey Blumer
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors' goal was to study the serum sertraline levels of breast-feeding mothers and their infants. METHOD: They obtained serum levels of sertraline and N-desmethylsertraline in nine mother-infant pairs. RESULTS: Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or less) in seven of the nine infants. One infant had a high level of N-desmethylsertraline, and one infant had unusual serum sertraline and N-desmethylsertraline values (half of its mother's levels). All infants were thriving. CONCLUSIONS: Most breast-feeding infants whose mothers were taking sertraline had very low serum levels of both sertraline and N-desmethylsertraline, consistent with published reports. The authors discuss in detail the one infant with unusually high levels.