tbuckley/cabot-search huggingface dataset:
Treatment of Leptomeningeal Metastases Evaluated by Interphase Cytogenetics
Authors: R.J. van Oostenbrugge, A.H. N. Hopman, J.W. Arends, F.C. S. Ramaekers, A. Twijnstra
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Although cytologic examination of CSF is the primary method for the evaluation of response to therapy for leptomeningeal metastases (LMMs), the procedure’s sensitivity decreases throughout the course of protracted therapy. We studied whether this response could be monitored more accurately through the detection of numerical chromosomal aberrations by interphase cytogenetics, using fluorescence in situ hybridization (FISH). PATIENTS AND METHODS: Seven patients treated for LMMs and with a known numerical aberration for chromosome 1 in their pretreatment CSF were included in this study. Up to 16 consecutive CSF samples were analyzed by means of the fluorescence in situ hybridization (FISH) technique for cells with aberrant chromosome 1 content. The results of routine cytology and FISH analyses were compared and were correlated with each patient’s neurologic status. RESULTS: Routine cytology detected malignancies in only 24 of the 76 samples, all of which were classified as chromosomally abnormal by FISH (except for two samples that could not be evaluated). Moreover, FISH demonstrated aneusomic cells in 32 additional samples, which could therefore be classified as malignant. The FISH results correlated better with patient neurologic status in that more malignant cells were detected in the CSF of neurologically deteriorating patients. CONCLUSION: Using FISH in addition to performing routine cytologic examination of CSF led to a more accurate evaluation of response to treatment in patients treated for LMMs.
Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort
Authors: Jacques-Eric Gottenberg, Jean-Michel Dayer, Cedric Lukas, Beatrice Ducot, Gilles Chiocchia, Alain Cantagrel, Alain Saraux, Pascale Roux-Lombard, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the level of serum markers of B cell activation. <h3>Methods</h3> Serum interleukin (IL)-1β, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon γ levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for &gt;6 weeks and &lt;6 months, and no previous corticosteroids or disease-modifying antirheumatic drugs. Serum cytokine levels were compared between patients who met the 1987 American College of Rheumatology criteria for RA (n=578) or had undifferentiated arthritis (UA, n=132) at the 1-year follow-up visit. <h3>Results</h3> Serum IL-6 and IL-21 were the only cytokines that discriminated RA from UA on univariate analysis. IL-6 level was associated with RA, whereas erythrocyte sedimentation rate and C-reactive protein were not. Higher proportions of rheumatoid factor and anticyclic citrullinated protein (CCP) positivity, levels of markers of B cell activation, and a higher frequency of rapid radiographic progression were observed in patients with RA with detectable IL-6 or IL-21. Multivariate analysis associated IL-6 and anti-CCP levels with radiographic erosions at enrolment with 1-year radiographic progression. <h3>Conclusion</h3> Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.
Effect of Asbestos, and of Asbestos and Aluminium, on the Lungs of Rabbits
Authors: E. J. King, J. W. Clegg, V. M. Rae
Journal: Thorax (1946)

The purpose of these experiments was to test two questions: (a) whether short- fibre asbestos is less damaging in the lungs of the rabbit than is long-fibre asbestos, and (b) whether metallic aluminium will suppress any toxic effect produced by either the shortor long-fibre asbestos.Early work with experimental asbestosis in animals has led Gardner, of Saranac Lake (Gardner, 1937(Gardner, , 1938(Gardner, , and 1940)), to suggest a "mechanical" theory of asbestosis.In contrast to quartz and other forms of free silica, which appeared to become more toxic as their particle size decreased, the shorter the fibre of the asbestos dust used, the less tissue reaction was produced.In fact, asbestos dust which had been well ground in order to eliminate all long fibre produced almost no pathogenic effects in tissue at all.On the other hand, long-fibre asbestos, or the presence of long-fibre particles amongst dust of finer size, produced a diffuse fibrous response.The pathogenic effect with long-fibre asbestos, however, was obtained only in the lungs.In all other tissues asbestos of any length appeared to produce nothing other than a foreign-body reaction.These facts led Gardnei to conclude that it was only.intissue where rhythmic movement takes place that asbestos can exert a pathogenic action, and then only if the particles are of sufficient size to produce mechanical irritation.
The management of immunosuppression in patients with inflammatory bowel disease and cancer
Authors: Oren Bernheim, Jean-Frederic Colombel, Thomas A Ullman, David Laharie, Laurent Beaugerie, Steven H Itzkowitz
Journal: Gut (2013)

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. Immunomodulators and biologic agents (hereafter referred to jointly as ‘immunosuppression’) are effective in treating IBD and recent evidence supports their introduction earlier in the disease course.1 ,2 An important concern to both patients and physicians considering immunosuppression for the treatment of IBD is the potential associated cancer risk.

It is estimated that 1.6 million new diagnoses of cancer will be made in 2013 among the general population in the USA alone.3 Likewise, as the population of patients with IBD ages, it is inevitable that some will develop cancer. As such, in addition to concerns about the development of de novo cancer in a patient without a history of cancer, clinicians caring for patients with IBD are increasingly challenged with questions about IBD management after the development of cancer. Conversely, oncologists are often concerned about how to manage IBD in cancer patients.

Several important clinical questions deserve further attention with respect to IBD therapy and cancer (figure 1). First, does medical therapy for IBD predispose to developing cancer? Second, in an IBD patient with a history of cancer, does IBD therapy impact cancer recurrence? Third, once cancer develops in an IBD patient, is the cancer outcome different? Finally, in an IBD patient with current cancer, does the cancer therapy affect IBD outcomes?



Figure 1 
Clinical questions related to patients with inflammatory bowel disease and cancer. IBD, inflammatory bowel disease; TNF, tumour necrosis factor.



Question 1, dealing with the topic of de novo cancer development related to treatments for IBD in patients without a history of cancer, has recently been reviewed.4 Less is known about the impact of immunosuppressive therapies on cancer in IBD patients who have had a prior (controlled) cancer or have a current (uncontrolled) cancer. …
The Thioredoxin-1 Inhibitor 1-Methylpropyl 2-Imidazolyl Disulfide (PX-12) Decreases Vascular Permeability in Tumor Xenografts Monitored by Dynamic Contrast Enhanced Magnetic Resonance Imaging
Authors: Bénédicte F. Jordan, Matthew Runquist, Natarajan Raghunand, Robert J. Gillies, Wendy R. Tate, Garth Powis, Amanda F. Baker
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The purpose of this study was to use dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to measure changes in tumor xenograft permeability produced by the antitumor thioredoxin-1 (Trx-1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) and to assess the relationship to Trx-1 and vascular endothelial growth factor (VEGF) levels. Experimental Design: DCE-MRI was used to monitor the dynamics of gadolinium-diethylenetriaminepentaacetic acid coupled bovine serum albumin as a macromolecular contrast reagent to measure hemodynamic changes in HT-29 human colon xenografts in immunodeficient mice treated with PX-12. Blood vessel permeability was estimated from the slope of the enhancement curves, and tumor vascular volume fraction from the ordinate. Tumor Trx-1 and VEGF was also measured. Results: PX-12 caused a rapid 63% decrease in the average tumor blood vessel permeability within 2 hours of administration. The decrease lasted 24 hours and had returned to pretreatment values by 48 hours. The changes in vascular permeability were not accompanied by alterations in average tumor vascular volume fraction. There was a decrease in tumor and tumor-derived VEGF in plasma at 24 hours after treatment with PX-12, but not at earlier time points. However, tumor redox active Trx-1 showed a rapid decline within 2 hours following PX-12 administration that was maintained for 24 hours. Conclusion: The rapid decrease in tumor vascular permeability caused by PX-12 administration coincided with a decrease in tumor redox active Trx-1 and preceded a decrease in VEGF. DCE-MRI responses to PX-12 in patients of Trx-1 inhibition at early time points and decreased VEGF at later times, may be useful to follow tumor response and even therapeutic benefit.
Glycemic Treatment in Type 1 and Type 2 Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2006)

This is the second in a series of articles on presentations at the American Diabetes Association’s 66th Scientific Sessions, Washington, DC, 9–13 June 2006.

A pilot project is underway to offer the Perspectives on the News commentaries as a monthly Web-based CME activity. Please access www.ada.procampus.net to view our initial efforts. We look forward to your comments.

At the meeting of the Council on Nutritional Science and Metabolism, Joan V.C. Hill (Natick, MA) introduced a session addressing the implications of postprandial blood glucose monitoring by reminding the audience that the American Diabetes Association (ADA) recommends a target HbA1c (A1C) of ≤7% but that the most recent National Health and Nutrition Examination Survey suggests that >60% of persons with diabetes fail to meet this goal. In a Quest laboratories analysis of 14.3 million A1C tests performed for diabetes diagnosis codes, half were shown to be above goal, although the average decreased from 7.8% in 2001 to 7.2% in 2005. An important question is the contribution of postprandial blood glucose to A1C, with the corollary being the determination of reasonable postprandial blood glucose targets, with Hill asking whether targeting postprandial blood glucose can improve metabolic control or, more importantly, improve outcome, recognizing the difficulty of determining the relationship between postprandial blood glucose and outcome. “The clear message,” Hill concluded, is that “achieving A1C close to goal [will require] monitoring postprandial glucose.”

Martin Abrahamson (Boston, MA) reminded the audience, “Most of our lives are spent in the postprandial state,” with the preprandial state not beginning until 10 h after ingestion of food, perhaps in most persons only from 4:00 to 8:00 a.m. Thus, measurement of fasting glucose may represent a state not particularly representative of that encountered through the day. To achieve the target goal of A1C as close to normal …
Guanylate cyclase C signaling: an intestinal secretory pathway where bugs, genes and new drugs intersect
Authors: Michael Camilleri
Journal: Genome Medicine (2012)

Acute infectious and chronic diarrheal diseases are important public health problems. A recent study by Fiskerstrand and colleagues identified a family with a rare early onset familial diarrhea. By linkage analysis and exon sequencing, the authors identified a heterozygous missense mutation in GUCY2C, encoding the guanylate cyclase C receptor, which is involved in intestinal secretion. This newly identified gene in the etiology of a familial diarrhea provides a candidate target for the development not only of new treatments for diarrhea, but also of a new drug class to treat constipation.
Prostanoid synthesis by cultured intestinal epithelial and mononuclear cells in inflammatory bowel disease.
Authors: A Zifroni, A J Treves, D B Sachar, D Rachmilewitz
Journal: Gut (1983)

Intestinal epithelial and mononuclear cells were isolated from normal colonic mucosa and from intestinal mucosa of inflammatory bowel disease patients. Prostanoid synthesis by primary cultures of intestinal mononuclear cells were four to six fold higher than its synthesis by primary cultures of epithelial cells. Prostaglandin E2, prostacyclin and thromboxane A2 synthesis by cultured mononuclear cells isolated from inflamed ileal mucosa of four Crohn9s disease patients: 5.6 +/- 1.2; 3.2 +/- 1.9 and 2.4 +/- 1.4 (mean +/- SE) ng/1 X 10(6) cells were significantly higher than their respective synthesis by cultured mononuclear cells isolated from uninflamed ileal mucosa isolated from the same patients: 0.8 +/- 0.1; 0.3 +/- 0.1 and 0.2 +/- 0.03 ng/1 X 10(6) cells or from normal colonic mucosa: 1.5 +/- 0.3; 0.3 +/- 0.1 and 0.5 +/- 0.1 (N = 12) ng/1 X 10(6) cells. Prostanoid synthesis by primary cultures of intestinal mononuclear cells isolated from colonic mucosa of five ulcerative colitis patients was enhanced but not significantly different from its synthesis by cells isolated from normal subjects. These results suggest that the enhanced intestinal prostanoid synthesis in active Crohn9s disease is derived from stimulated local mononuclear cells and may have an important role in the pathogenesis of the disease.
Tuberculosis treatment outcome monitoring in European Union countries: systematic review
Authors: Rob van Hest, Csaba Ködmön, Suzanne Verver, Connie G.M. Erkens, Masja Straetemans, Davide Manissero, Gerard de Vries
Journal: European Respiratory Journal (2012)

Treatment success measured by treatment outcome monitoring (TOM) is a key programmatic output of tuberculosis (TB) control programmes. We performed a systematic literature review on national-level TOM in the 30 European Union (EU)/European Economic Areas (EEA) countries to summarise methods used to collect and report data on TOM. Online reference bibliographic databases PubMed/MEDLINE and EMBASE were searched to identify relevant indexed and non-indexed literature published between January 2000 and August 2010. The search strategy resulted in 615 potentially relevant indexed citations, of which 27 full-text national studies (79 data sets) were included for final analysis. The selected studies were performed in 10 EU/EEA countries and gave a fragmented impression of TOM in the EU/EEA. Publication year, study period, sample size, databases, definitions, variables, patient and outcome categories, and population subgroups varied widely, portraying a very heterogeneous picture. This review confirmed previous reports of considerable heterogeneity in publications of TOM results across EU/EEA countries. PubMed/MEDLINE and EMBASE indexed studies are not a suitable instrument to measure representative TOM results for the 30 EU/EEA countries. Uniform and complete reporting to the centralised European Surveillance System will produce the most timely and reliable results of TB treatment outcomes in the EU/EEA.
Limits of teacher delivered sex education: interim behavioural outcomes from randomised trial
Authors: D. Wight
Journal: BMJ (2002)

To determine whether a theoretically based sex education programme for adolescents (SHARE) delivered by teachers reduced unsafe sexual intercourse compared with current practice.Cluster randomised trial with follow up two years after baseline (six months after intervention). A process evaluation investigated the delivery of sex education and broader features of each school.Twenty five secondary schools in east Scotland.8430 pupils aged 13-15 years; 7616 completed the baseline questionnaire and 5854 completed the two year follow up questionnaire.SHARE programme (intervention group) versus existing sex education (control programme).Self reported exposure to sexually transmitted disease, use of condoms and contraceptives at first and most recent sexual intercourse, and unwanted pregnancies.When the intervention group was compared with the conventional sex education group in an intention to treat analysis there were no differences in sexual activity or sexual risk taking by the age of 16 years. However, those in the intervention group reported less regret of first sexual intercourse with most recent partner (young men 9.9% difference, 95% confidence interval -18.7 to -1.0; young women 7.7% difference, -16.6 to 1.2). Pupils evaluated the intervention programme more positively, and their knowledge of sexual health improved. Lack of behavioural effect could not be linked to differential quality of delivery of intervention.Compared with conventional sex education this specially designed intervention did not reduce sexual risk taking in adolescents.
Basal Subtype and MAPK/ERK Kinase (MEK)-Phosphoinositide 3-Kinase Feedback Signaling Determine Susceptibility of Breast Cancer Cells to MEK Inhibition
Authors: Olga K. Mirzoeva, Debopriya Das, Laura M. Heiser, Sanchita Bhattacharya, Doris Siwak, Rina Gendelman, Nora Bayani, Nicholas J. Wang, Richard M. Neve, Yinghui Guan, Zhi Hu, Zachary Knight, Heidi S. Feiler, Philippe Gascard, Bahram Parvin, Paul T. Spellman, Kevan M. Shokat, Andrew J. Wyrobek, Mina J. Bissell, Frank McCormick, Wen-Lin Kuo, Gordon B. Mills, Joe W. Gray, W. Michael Korn
Journal: Cancer Research (2009)

Abstract Specific inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) have been developed that efficiently inhibit the oncogenic RAF-MEK-ERK pathway. We used a systems-based approach to identify breast cancer subtypes particularly susceptible to MEK inhibitors and to understand molecular mechanisms conferring resistance to such compounds. Basal-type breast cancer cells were found to be particularly susceptible to growth inhibition by small-molecule MEK inhibitors. Activation of the phosphatidylinositol 3-kinase (PI3K) pathway in response to MEK inhibition through a negative MEK-epidermal growth factor receptor-PI3K feedback loop was found to limit efficacy. Interruption of this feedback mechanism by targeting MEK and PI3K produced synergistic effects, including induction of apoptosis and, in some cell lines, cell cycle arrest and protection from apoptosis induced by proapoptotic agents. These findings enhance our understanding of the interconnectivity of oncogenic signal transduction circuits and have implications for the design of future clinical trials of MEK inhibitors in breast cancer by guiding patient selection and suggesting rational combination therapies. [Cancer Res 2009;69(2):565–72]
Widespread Colonization of the Lung by <i>Tropheryma whipplei</i> in HIV Infection
Authors: Catherine Lozupone, Adela Cota-Gomez, Brent E. Palmer, Derek J. Linderman, Emily S. Charlson, Erica Sodergren, Makedonka Mitreva, Sahar Abubucker, John Martin, Guohui Yao, Thomas B. Campbell, Sonia C. Flores, Gail Ackerman, Jesse Stombaugh, Luke Ursell, James M. Beck, Jeffrey L. Curtis, Vincent B. Young, Susan V. Lynch, Laurence Huang, George M. Weinstock, Kenneth S. Knox, Homer Twigg, Alison Morris, Elodie Ghedin, Frederic D. Bushman, Ronald G. Collman, Rob Knight, Andrew P. Fontenot
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Lung infections caused by opportunistic or virulent pathogens are a principal cause of morbidity and mortality in HIV infection. It is unknown whether HIV infection leads to changes in basal lung microflora, which may contribute to chronic pulmonary complications that increasingly are being recognized in individuals infected with HIV.To determine whether the immunodeficiency associated with HIV infection resulted in alteration of the lung microbiota.We used 16S ribosomal RNA targeted pyrosequencing and shotgun metagenomic sequencing to analyze bacterial gene sequences in bronchoalveolar lavage (BAL) and mouths of 82 HIV-positive and 77 HIV-negative subjects.Sequences representing Tropheryma whipplei, the etiologic agent of Whipple's disease, were significantly more frequent in BAL of HIV-positive compared with HIV-negative individuals. T. whipplei dominated the community (>50% of sequence reads) in 11 HIV-positive subjects, but only 1 HIV-negative individual (13.4 versus 1.3%; P = 0.0018). In 30 HIV-positive individuals sampled longitudinally, antiretroviral therapy resulted in a significantly reduced relative abundance of T. whipplei in the lung. Shotgun metagenomic sequencing was performed on eight BAL samples dominated by T. whipplei 16S ribosomal RNA. Whole genome assembly of pooled reads showed that uncultured lung-derived T. whipplei had similar gene content to two isolates obtained from subjects with Whipple's disease.Asymptomatic subjects with HIV infection have unexpected colonization of the lung by T. whipplei, which is reduced by effective antiretroviral therapy and merits further study for a potential pathogenic role in chronic pulmonary complications of HIV infection.
<i>miR-146a</i> Suppresses Invasion of Pancreatic Cancer Cells
Authors: Yiwei Li, Timothy G. VandenBoom, Zhiwei Wang, Dejuan Kong, Shadan Ali, Philip A. Philip, Fazlul H. Sarkar
Journal: Cancer Research (2010)

The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-kappaB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-kappaB regulatory kinase interleukin 1 receptor-associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IkappaBalpha, NF-kappaB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3'-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-kappaB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents.