tbuckley/cabot-search huggingface dataset:
Abstract 157: Variability of microRNA measurements in breast ductal carcinomas
Authors: William E. Grizzle, Elizabeth H. Kerr, Suzanne B. Parker, Denise K. Oelschlager, Lacey R. McNally
Journal: Cancer Research (2011)

Abstract MicroRNAs (miRNAs) are a newly identified class of molecules involved in the post transcriptional regulation of genetic information. Multiple approaches have been developed to measure miRNAs including the measurement of miRNAs in paraffin embedded tissue. There have been few reported studies of the reproducibility of miRNA measurements, especially in paraffin embedded tissues, and how such measurements might vary due to tissue heterogeneity and/or analytical variability. We used microdissected paraffin embedded samples of ductal carcinoma of the breast enriched to a tumor nuclear cellularity of at least 80% to determine the reproducibility of analysis of miRNAs extracted from paraffin sections. From each of 3 microdissected paraffin embedded tissues, six 10μ paraffin sections were cut and combined as one specimen and the following six 10μ sections were combined as a second specimen from the same case. While the sections were adjacent, this would incorporate variation due to tissue heterogeneity over 0.12mm of the specimen that was analyzed. All six specimens were blinded and 1500 miRNAs including miRNAs from mice, rats and plants as controls were analyzed by High Throughput Genomics (HTG) considering each of these 6 specimens as an independent specimen. Even with tissue heterogeneity, the correlations of the values of miRNA of the three pairs of specimens were 0.96, 0.90 and 0.83; the 12 correlations between specimens of different cases did not excel 0.9 and only 2 exceeded 0.8. Results of combining alternative paraffin sections into 2 specimens from these same cases and laser capture microdissection specimens are pending to separate differences due to variation in tissue from analytical variables. Of note, the 22 most upregulated miRNAs (X20 to X30 basal levels) in these breast ductal carcinomas include the following: Let 7b, Let 7f, 1225-3P, 1228, 1237, 1280, 1281, 1308, 16, 1826, 191, 200c, 23a, 27a, 574-5p, 638, 663b, 720, 768-3P, 768-5P, 886-5P, and 92a. These studies are continuing and laser capture microdissection results will be incorporated in the study. Supported in part by the Breast SPORE at UAB (CA089019-09) and a grant from the Susan G Komen foundation (BCTR0600484). 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 157. doi:10.1158/1538-7445.AM2011-157
Abstract 608: Oncogenic role of cullin 4 E3 ubiquitin ligase (CRL4-CDT2) in epithelial ovarian cancer
Authors: Kari E. Ring, Tarek Abbas, Jennifer Bryant, Anindya Dutta, Amir A. Jazaeri
Journal: Cancer Research (2011)

Abstract Objective: Ubiquitination is a key posttranslational modification involved in the tight regulation of biological processes including cell-cycle regulation and DNA replication and repair. Our objective was to investigate the expression and function of CDT2, a substrate recognition factor for the CUL4 E3 ubiquitin ligase family (CRL4-CDT2) in ovarian cancer. Methods: CDT2 expression was evaluated using realtime RT-PCR in 26 serous ovarian cancers 11 normal ovaries, and 14 fallopian tube fimbria specimens and confirmed by Western blotting on a subset of the above. Immunohistochemistry was performed using tissue microarrays consisting of over 130 independent ovarian cancer samples of various histologies, as well as, normal fallopian tube samples using antibodies to CDT2 and p21. Each samples was represented at least in triplicate and scored semi-quantitatively. CDT2 knockdown was accomplished using siRNA and overexpression via retroviral transduction. Cell growth was evaluated using MTT assays. Statistical analysis were performed using either parametric (t test) as well as non-parametric (Mann-Whitney and Kruskal Wallis) methods as indicated. Comparison of p21 and CDT2 expression was performed using Spearman's correlation. Results: CDT2 mRNA expression was approximately 9 fold higher in serous ovarian cancers compared to normal ovary and fallopian tube fimbria samples (P&amp;lt;0.00001). Western blotting confirmed this differential expression at the protein level. Immunohistochemistry validated CDT2 overexpression in ovarian cancers and did not reveal any differences between serous and other histological subtypes. Immunohistochemical staining did not reveal any significant correlation between the expression of CDT2 and p21, a previously identified target of CRL4-CDT2. Knockdown of CDT2 expression resulted in 31% reduction in cell viability in high CDT2 expressing ES2 cells (P&amp;lt;0.0001) but had minimal effect in low CDT2 expressing SKOV3 cells. However, overexpression of CDT2 in SKOV3 cells did not influence growth of these cells. Knockdown of other component of CRL4-CDT2 ubiquitin ligase (Cul4A and DDB1) also reduced growth of ES2 cells. Finally CDT2 protein levels significantly increased upon in vitro transformation of fallopian tube epithelial cells (described elsewhere) and in subsequent mouse xenografts established from these cells. Conclusions: The results of this ongoing investigation are the first to suggest an oncogenic role for the CRL4-CDT2 ubiquitin ligase in ovarian cancer. The mechanism of action remains unknown but does not appear to involve p21 degradation. 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 608. doi:10.1158/1538-7445.AM2011-608
Disturbance of HL-A Antigen Frequency in Psoriasis
Authors: Seymour H. White, Victor D. Newcomer, Max R. Mickey, Paul I. Terasaki
Journal: New England Journal of Medicine (1972)

One hundred and fifty-six psoriatic patients had three HL-A specificities significantly altered from expected values; W17 and HL-A13 were found to be markedly increased, and HL-A12 decreased. The increased frequency of W17 and HL-A13 suggests that persons with these tissue types are at increased risk of the disease. Conversely, those with HL-A12 are at decreased risk. W17 is a useful genetic marker for detecting a subgroup of psoriatic patients characterized by a high rate of affected relatives and a slightly earlier age at onset, whereas HL-A12 appears to detect a subgroup with an infrequent family history of this disease. Psoriasis associated with W17 or HL-A12 appears to have a distinctive mode of inheritance, whereas psoriasis associated with HL-A13 could not be shown to be inherited. No significant association with arthritis, severity, distribution of lesions, sex, and red-cell type was noted.
Commentary: Methodologic Approaches to Studying Environmental Factors in Childhood Cancer
Authors: Seymour Grufferman
Journal: Environmental Health Perspectives (1998)

Little is known about environmental causes of childhood cancer.This is probably due to the relative rarity of cancer in children.In the United States, cancer incidence in adults is over 20 times greater than cancer incidence in children.The situation is compounded by the fact that two groups of cancers, leukemias and brain and spinal tumors, account for half of all childhood cancers.The rarity of childhood cancer renders the conduct of most cohort studies infeasible.The majority of studies assessing potential environmental risk factors for childhood cancers have been case-control studies, which are highly efficient for studying rare diseases.Case-control studies of childhood cancers have been greatly facilitated by using cooperative clinical trial groups for case identification.The national studies that have emerged utilize random-digit telephone dialing and telephone interviewing as feasible and economic means of identifying and interviewing controls.Other approaches such as descriptive epidemiology, ecologic studies, and studies of cancer clusters have proven to be disappointing in elucidating environmental causes of childhood cancer.Descriptive and ecologic studies provide no information on specific exposures of study subjects; rather, they use population levels as surrogates for individual exposure.Studies of cancer clusters have also proven to be disappointing.Although there are numerous difficulties in conducting research on the causes of childhood cancer, these difficulties can be remedied by using carefully designed and conducted studies.It should be remembered that the epidemiologic approach is probably the most likely research venue for uncovering environmental causes of childhood cancer.
Solid Cancers after Bone Marrow Transplantation
Authors: Rochelle E. Curtis, Philip A. Rowlings, H. Joachim Deeg, Donna A. Shriner, Gérard Socié, Lois B. Travis, Mary M. Horowitz, Robert P. Witherspoon, Robert N. Hoover, Kathleen A. Sobocinski, Joseph F. Fraumeni, John D. Boice, H. Gary Schoch, George E. Sale, Rainer Storb, William D. Travis, Hans-Jochem Kolb, Robert Peter Gale, Jakob R. Passweg
Journal: New England Journal of Medicine (1997)

The late effects of bone marrow transplantation, including cancer, need to be determined in a large population at risk.
P462Metabolic control of microvascular networks: oxygen sensing and beyond
Authors: B Reglin, AR Pries
Journal: Cardiovascular Research (2014)

Purpose: Metabolic regulation of blood flow is central to guarantee adequate substrate supply of tissues and microvascular network stability. Vascular reactions to local oxygenation are assumed to match blood supply to tissue demand in steady state and in response to exercise and/or tissue hypoxia via negative feedback regulation: Low oxygen tension is assumed to induce the release of vasoactive substances which trigger increase of vessel number and diameter and thus of blood flow and oxygen supply (angioadaptation). Here, we try to integrate experimental and modelling findings to derive general schemes of metabolic regulation of angioadaptation, with a focus on control of vessel diameter.
Just the facts, and only the facts, about human rationality?
Authors: Jeffrey Foss
Journal: Behavioral and Brain Sciences (2011)

Abstract Elqayam &amp; Evans' (E&amp;E's) laudable program to keep the scientific investigation of human reasoning norm-free and focused on the facts alone is an essential part of a long tradition in the philosophy of science – but it faces deeper difficulties than the authors seem to realize, since reasoning is a competence, and the very concept of competence is normative.
The Effect of Injury to the Spinal Cord and Cauda Equina on the Sexual Potency of Men
Authors: Donald Munro, Herbert W. Horne, David P. Paull
Journal: New England Journal of Medicine (1948)

PATIENTS who are paralyzed as the result of an injury to the spinal cord or cauda equina have to face many difficult physical and psychologic problems. One of the most difficult of the psychologic ones is that which has to do with their loss of sexual ability. To discuss it at all with their doctors requires mutual understanding and confidence. Such confidence presupposes knowledge on the part of the physicians — that is, knowledge of the effect of a cord injury on the various aspects of sexual and possibly married life. Unfortunately, such basic information is conspicuous by its absence. . . .
Abstract SY05-01: Biological and clinical activities of FDA-approved drugs that antagonize Hh signaling
Authors: James Kim, Jean Y. Tang
Journal: Cancer Research (2011)

Abstract The inappropriate activity of the Hedeghog (Hh) signaling pathway noted in a variety of tumor types has prompted efforts to develop small molecule antagonists of Hh pathway signaling. The use of FDA-approved drugs as Hh pathway antagonists may avoid some of the expense and delay associated with de novo development of Hh pathway antagonists. We have identified two FDA-approved drugs, itraconazole and arsenic trioxide, as potent inhibitors of the Hh pathway in vitro and in vivo at the level of Smoothened (Smo) and Gli, respectively. In addition, both itraconazole and arsenic trioxide have inhibitory activity against a mutant Smoothened resistant to GDC-0449, a potent Smo antagonist. These preclinical studies have led to a pilot clinical trial (ID: NCT01108094) using itraconazole for patients with basal cell carcinoma, a skin tumor that is driven by the Hh pathway. We have treated 13 subjects with 200mg of itraconazole twice daily and found -32% (95% CI: -19 to -42%) reduction in tumor diameter in 1 month. These studies suggest that FDA-approved drugs show promise as Hh pathway antagonists for the treatment of Hh-dependent cancers and warrant further study. 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 SY05-01. doi:10.1158/1538-7445.AM2011-SY05-01
P156 NAEDI lung cancer awareness campaign in London
Authors: A. Safa, A. Berry, H. Ali, J. Car, E. F. Bowen
Journal: Thorax (2011)

<h3>Background</h3> Lung cancer is the leading cause of cancer mortality in the UK. Survival rates over the last 30 years have not significantly improved. The NAEDI initiative is working to promote early diagnosis to improve stage at presentation and increase survival rates. <h3>Objectives</h3> The project in Hammersmith &amp; Fulham focused on the three most deprived wards, population 32 000). The aims were to increase public awareness and intention to act on symptoms by 10%, GP chest x-ray referrals by 15%, and Two Week Rule (TWR) referrals and, ultimately, earlier stage at diagnosis by 10%. <h3>Methods</h3> Nine general practices in the target area received educational seminars on NICE guidelines, project details and aims. 40 pharmacies, 25 smoking cessation advisors and 30 district nurses received education on symptoms, communication and management skills, and were provided with campaign materials. The public campaign involved training 42 health champions in key messages regarding alarm symptoms. Face-to-face contact was made with 1300 people. Local advertising had an estimated reach of three million people. The campaign ran from February to July 2011. <h3>Results</h3> Data on public perceptions were collected with a validated form of the Cancer Awareness Measure. On average there was a 12% increase in unprompted recall of the commonest lung cancer symptoms, and a 26% increase in intention to make urgent GP contact for such symptoms. Data from the 9 practices during the campaign period in 2011 compared to the same period in 2010 showed a rise in chest x-ray referrals from 350 to 463 (32% increase). In 2010 there were no TWR referrals and seven lung cancer diagnoses. For 2011, there was 1 TWR referral (lung cancer) and 10 new lung cancers diagnosed. <h3>Conclusions</h3> Community engagement has been a success locally with active involvement of trained champions into future public health work streams. Data collection again next year is required to evaluate whether the increase in chest x-ray referral rates is maintained and translated into earlier stage at diagnoses. The success of primary care engagement needs roll out across the borough and embedding into future service provision to ensure sustainability.
M268 The Ipf Diagnosis - Communicating A Life Sentence
Authors: S. Wibberley, Y. Ochiai, R. Pitt, N. Mathieson
Journal: Thorax (2014)

<h3>Background</h3> The aim was to explore the patients’ emotional experience of receiving a diagnosis of IPF. <h3>Methods</h3> Market research was conducted with an independent agency. Patients with IPF were asked to record a personal account of their experience on a hand-held camera. Face to face interviews with patients were conducted in their home. Carers were also interviewed to add an alternative perspective. <h3>Results</h3> The sample included 13 male and 3 female patients with IPF. Patients with lung function impairment of all severities were included, five patients were treated with oxygen therapy and another had received a lung transplant. There was a national spread geographically throughout England. There is a fine balance to providing information and patients can benefit from an individually tailored approach. Too much information at the start can be overwhelming. Too little information can leave the individual uncertain about how to deal with their future. Gaps that were identified focused on the practicalities of living with IPF, including social care. There was a high expectation for their physician to explain the trigger for developing IPF. Patients felt a blame culture exists, whereby others felt that IPF is self-inflicted, like COPD, particularly when a patient was taking oxygen therapy. Patients may be left with feelings of anger at missed opportunities and concern for lost years of intervention and appropriate palliative care support. <h3>Conclusions</h3> The diagnosis of IPF is a devastating one, which can be challenging to manage. Carers, patient groups and expert support at diagnosis were found to be invaluable to patients during this time.
SAT0204 Predictors for SLE flares: Baseline disease activity and demographic characteristics from the bliss trials’ combined placebo groups:
Authors: R.F. van Vollenhoven, M. Petri, R.A. Levy, S. Navarra, J. Buyon, Z.J. Zhong, W. Freimuth, R. Cervera
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Predicting which SLE patients are at increased risk for clinically meaningful flares may be useful in making management decisions. <h3>Objectives</h3> To identify demographic and disease-related predictors for flares. <h3>Methods</h3> Baseline demographic and SLE-related disease activity characteristics were evaluated for their ability to predict new SLE flares by wk 24 in the combined dataset of 562 patients receiving placebo + standard therapy from the belimumab BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) phase 3 trials. Flare (moderate-severe) was defined according to the modified SLE Flare Index (SFI) or as the development of 1 new BILAG A or 2 new B organ domain scores. Baseline variables included race, age, gender, BMI, SELENA-SLEDAI (SS; mean score, range, and 24 items with ≥30/group), PGA, BILAG A-E scores, ACR diagnostic criteria, SLICC damage index, SLE duration, and concurrent medications. A ≥10% absolute difference (% flare - % no flare) or ≥50% increase ([% flare - % no flare]/% no flare) was considered clinically meaningful. <h3>Results</h3> By wk 24, 142 patients (25.3%) receiving placebo had a flare by BILAG and 72 (12.8%) by SFI. By both flare indices, SS ≥12, serologic markers, and moderate-severe disease activity involving renal, hematologic, and vasculitic domains were predictors of flare, as was prednisone use (table). Immunosuppressives, antimalarials, and other concomitant medications did not predict flare. <h3>Conclusions</h3> SLE patients on standard therapy alone with moderate-severe renal, vasculitic, hematologic, or serologic disease activity were at increased risk of having a clinically meaningful flare over 24 wk. <h3>Disclosure of Interest</h3> R. van Vollenhoven Grant/Research support from: GlaxoSmithKline/Human Genome Sciences, M. Petri Consultant for: GlaxoSmithKline/Human Genome Sciences, R. Levy Speakers Bureau: GlaxoSmithKline/Human Genome Sciences, S. Navarra Speakers Bureau: GlaxoSmithKline/Human Genome Sciences, J. Buyon Grant/Research support from: Human Genome Sciences, Consultant for: GlaxoSmithKline/Human Genome Sciences, Z. Zhong Shareholder of: Human Genome Sciences, Employee of: Human Genome Sciences, W. Freimuth Shareholder of: Human Genome Sciences, Employee of: Human Genome Sciences, R. Cervera Grant/Research support from: GlaxoSmithKline/Human Genome Sciences, Consultant for: GlaxoSmithKline/Human Genome Sciences
P5-14-15: Prognostic Impact of Chemotherapy-Induced Amenorrhea (CIA) in Premenopausal Breast Cancer: A Meta-Analysis of Published Literatures.
Authors: J Lu, Q Zhou, W Yin
Journal: Cancer Research (2011)

Abstract Background: Various studies have reported inconsistent results on the prognostic effect of chemotherapy-induced amenorrhea (CIA) in premenopausal breast cancer. Therefore, we conducted a meta-analysis to assess the effect of CIA on prognosis of premenopausal women with breast cancer. Methods: The PubMed database was searched for all relevant studies published before March 2011. Relative risks (RRs) were used to estimate the association between CIA on various survival outcomes. Subgroup analyses were also performed by age, nodal status and hormone receptor (HR) status. Results: With thirteen eligible studies identified, this meta-analysis included 5790 cases and 2159 controls. This meta-analysis demonstrated that CIA was associated with improved DFS (RR= 0.39, 95%CI: 0.32∼0.47, p&amp;lt;0.001) and OS (RR= 0.30, 95%CI: 0.21∼0.44, p&amp;lt;0.001). In the subgroup analyses, the effect of CIA on DFS and OS also existed in HR-positive subjects (for OS, RR= 0.19, 95%CI: 0.07∼0.49, p=0.001; for DFS, RR= 0.47, 95%CI: 0.35∼0.63, p&amp;lt;0.001) while similar results failed to be observed in HR-negative patients (for OS, RR= 0.62, 95%CI: 0.07∼5.75, p=0.671; for DFS, RR= 1.48, 95%CI: 0.50∼4.37, p=0.474). Furthermore, significant difference was achieved between women with and without CIA, irrespective of age and nodal status.*** Conclusion: This meta-analysis clarifies that CIA might contribute to the improvement of prognosis in HR-positive premenopausal breast cancer patients, which is at least partially responsible for the benefit of adjuvant chemotherapy in premenopausal women through chemical castration. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-15.
Abstract LB-29: LKB1 tumor suppressor regulates AMP kinase/mTOR-independent cell growth and proliferation via the phosphorylation of Yap
Authors: Hoa B. Nguyen, Justin T. Babcock, Clark D. Wells, Lawrence A. Quilliam
Journal: Cancer Research (2012)

Abstract The liver kinase B1 (LKB1) tumor suppressor inhibits cell growth through its regulation of cellular metabolism and apical-basal polarity. The best understood mechanism whereby LKB1 limits cell growth is through activation of the AMP-activated-protein-kinase/mammalian-target-of-rapamycin (AMPK/mTOR) pathway to control metabolism. Since LKB1 is also required for polarized epithelial cells to resist hyperplasia it is anticipated to function through additional mechanisms. Recently, Yes-associated protein (Yap) has emerged as a transcriptional co-activator that modulates tissue homeostasis in response to cell-cell contact. Thus this study examines a possible connection between Yap and LKB1. Restoration of LKB1 expression in HeLa cells, which lack this tumor suppressor, or shRNA knockdown of LKB1 in 293T cells, demonstrated that LKB1 promotes Yap phosphorylation, nuclear exclusion, and proteasomal degradation. The ability of phosphorylation-defective Yap mutants to rescue LKB1 phenotypes, such as reduced cell proliferation and cell size, suggest that Yap inhibition contributes to LKB1 tumor suppressor function(s). Interestingly, LKB1 inhibited Yap independently of either AMPK or mTOR activation. These findings reveal a novel mechanism whereby LKB1 may restrict cancer cell growth via the inhibition of Yap. 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 LB-29. doi:1538-7445.AM2012-LB-29