tbuckley/cabot-search huggingface dataset:
Abstract A36: Nuclear NUAK1 function on cancer cell survival, independently of LKB1 and p53
Authors: Mario Palma, Daniela Peña, Katherine Venturelli, Ariel F. Castro
Journal: Cancer Research (2016)

Abstract Cancer cells evade cell death during tumor progression under metabolic stress. However, molecular mechanisms involved in cellular adaptation to this stress are still poorly understood. NUAK1, a serine threonine kinase of the AMPK catalytic subunit family, has been involved in tumor cell survival, but its regulation and function under metabolic stress remain unclear. For this study, we have used mouse embryo fibroblasts (MEFs) and cancer cells to better understand the role of NUAK1 in cell survival. We found that NUAK1 mRNA and protein levels increase in response to metabolic stress, suggesting a transcriptional regulation of NUAK1 expression. In addition, we found that NUAK1 is expressed almost exclusively in the nucleus of MEFs and several cancer cell lines. Because of the nuclear localization of NUAK1 and previous studies showing that NUAK1 regulates p53 transcription factor, we investigated whether p53 is necessary for NUAK1´s effect on cell survival. By using p53ER/ER MEFs that can be reversibly and rapidly switched between p53 wild-type and knockout states, we demonstrated that NUAK1 can promote cell survival in a p53-independent cellular context. Furthermore, NUAK1 was involved in cell survival of p53-null H1299 lung cancer and p53-null HCT116 colorectal cancer cells under metabolic stress. In parallel to the increase of NUAK1 expression, we found that NUAK1 is phosphorylated. LKB1 kinase is known to phosphorylate NUAK1, increasing NUAK1 kinase activity. However, shRNA-mediated depletion of LKB1 or mutation of the NUAK1 residue phosphorylated by LKB1 did not affect NUAK1 function on cell survival. By bioinformatics analysis of NUAK1 protein sequence, we found several sites predicted to be phosphorylated by JNK and p38. Future studies will determine whether JNK or p38 is involved in NUAK1 phosphorylation, and also evaluate whether NUAK1 nuclear localization is directly related with tumor progression in a p53-independent manner. Overall, our results showed that NUAK1 is transcriptional and post-translational regulated in response to metabolic stress, and that the effect of NUAK1 on cell survival is independently of LKB1 and p53. Funded by FONDECYT 1120923 Citation Format: Mario Palma, Daniela Peña, Katherine Venturelli, Ariel F. Castro. Nuclear NUAK1 function on cancer cell survival, independently of LKB1 and p53. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A36.
Evaluation of a Coronary Vasodilator
Authors: J D HARDY, F D KURRUS, C M CHAVEZ, W A NEELY, S ERASLAN, M D TURNER, L W FABIAN, T D LABECKI
Journal: JAMA (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Studies on the Influence of Age on the Latent-Period Response of Chickens to the Agent of Chicken Tumor I
Authors: Vernon T. Riley, Dorothy Calnan, W. Ray Bryan
Journal: JNCI Journal of the National Cancer Institute (1946)

Studies on the Influence of Age on the Latent-Period Response of Chickens to the Agent of Chicken Tumor I Vernon T. Riley, Vernon T. Riley assistant biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothy Calnan, Dorothy Calnan junior bacteriologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Ray Bryan W. Ray Bryan principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar 1The authors are indebted to Dr. C. I. Bliss, of the Connecticut Agricultural Experiment Station, for his guidance in the application of established statistical techniques to data of the type presented herein. Author Notes JNCI: Journal of the National Cancer Institute, Volume 7, Issue 2, October 1946, Pages 93–98, https://doi.org/10.1093/jnci/7.2.93 Published: 01 October 1946 Article history Published: 01 October 1946 Received: 07 October 1946
FRI0211 High Body Mass Index in Ankylosing Spondylitis is Associated with Greater Disease Activity and More Functional Impairmairment:
Authors: F.D. O'Shea, P. Gallagher, C. Sullivan, C. Sheehy, C. Silke, K. O'Rourke, F. Stafford, M. Haroon, R. Mullan, O. FitzGerald
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> In 2013, the first patients were entered in to ASRI – the Ankylosing Spondylitis Registry of Ireland. The primary objectives of ASRI are to provide basic descriptive epidemiological data on the Ankylosing Spondylitis (AS) population in Ireland, and to establish a registry for potential future studies of genetics, aetiology and therapeutics. <h3>Objectives</h3> In this current study we were interested in exploring the issue of obesity in an AS cohort, and the effect this has on disease activity and functional impairment. <h3>Methods</h3> A standardised detailed clinical assessment of patients is performed on each patient and entered in a web-based database. Specific measures of disease activity (BASDAI), function (BASFI and HAQ), and quality of life (ASQoL) were obtained. Body Mass Index (BMI) was calculated. The cohort was divided in to those of normal weight (BMI &lt;25), and those that were overweight or obese (BMI &gt;25). The 2 cohorts were compared using a number of different clinical variable using standard t-test. <h3>Results</h3> As of Dec 2014, 267 patients have been entered in the database (212 males, 55 females). The average age of the cohort is 47.8 years. The average disease duration is 21.7 years. The average delay in diagnosis is 8.2 years. As regards extra-spinal manifestations, 15.8% have Psoriasis, 40.4% have uveitis, 13% have Crohns/IBD. Of the 267 patients, 183 were overweight or obese (68.5%). There is a significant difference in BASFI scores between normal weight AS patients versus those that are overweight/obese. There is also a trend towards higher BASDAI, HAQ and ASQoL in those that are overweight/obese also. See Table below. There were a higher percentage of patients with Hypertension (30% versus 13%), Hyperlipidaemia (15% versus 7%) and Diabetes (7% versus 4%) in those that were overweight/obese. The rate of current or past smokers was very similar between the 2 cohorts, 57% (normal weight cohort) and 60% (overweight/obese cohort). <h3>Conclusions</h3> The majority of AS patients in our cohort were overweight or obese. These patients have a greater burden of symptoms and more functional impairment. They also have a higher percentage of other cardiovascular risk factors. As our awareness of the increased risk of cardiovascular disease in AS patients improves this is important information in on going management. <h3>Acknowledgements</h3> I would like to acknowledge Abbvie and Pfizer for the unrestricted support of ASRI. I would also like to acknowledge all the effort from the rheumatology community in Ireland for their hard work, enthusiasm and support of ASRI. <h3>Disclosure of Interest</h3> None declared
Spontaneous Tumors of the Nervous System in Albino Rats
Authors: James E. Fitzgerald, James L. Schardein, Stanley M. Kurtz
Journal: JNCI Journal of the National Cancer Institute (1974)

A retrospective review of necropsies of 7803 albino rats revealed 34 tumors originating in the brain or meninges for an overall incidence of 0.44%. In addition, 4 tumors of ganglion cell origin were found. The most frequent brain tumor was the astrocytoma. Other tumor types included oligodendroglioma, ependymoma, meningioma, ganglioneuroma, and optic nerve glioma. The tumors had a predeliction for male rats and occurred at an average age of 17–18 months.
Abstract B26: OIP5-Antisense 1, a long noncoding RNA deregulated in non-small cell lung cancer
Authors: Greg L. Stewart, Katey SS Enfield, David A. Rowbotham, Roland Hubaux, Victor Martinez, Stephen Lam, Wan Lam
Journal: Cancer Research (2016)

Abstract Background: Lung cancer represents an enormous health burden, representing the most common cause of cancer death worldwide. The poor therapeutic outcome is largely due to a complex molecular background as well as late stage diagnosis, with most patients presenting unresectable local tumors, or metastatic disease. While mutations of driver genes is a well-known mechanism, approximately half of all non-small cell lung cancer (NSCLC) tumors harbor no known clinically relevant oncogenic drivers, emphasizing the need to explore alternative mechanisms such as non-coding RNAs (ncRNAs). Natural antisense transcripts (NATS) are ncRNAs that are expressed from the opposite strand of coding mRNAs. These genes overlap with, and are often involved in the regulation of their sense counterparts. NATs can recruit regulatory complexes to their transcriptional locus, leading to silencing of transcription and have recently been described in cancer to silence tumor suppressor genes. NATs are quite prevalent as it is estimated that 25-40% of genes display overlapping transcription, however only a few NATs have been characterized, emphasizing the need to explore these ncRNAs in the context of NSCLC. Hypothesis: We hypothesize NATs of NSCLC-related genes are deregulated in NSCLC. Methods: We performed RNAseq and miRNAseq on a set of 65 NSCLC tumors including 36 adenocarcinomas and 29 squamous cell carcinomas as well as matched non-malignant lung tissue. A sign rank test was used to identify NATs with significantly altered expression between tumor and matched normal. Survival analysis was done using a Cox Proportional hazard model, as well as the Kaplan-Meier method. Results: We have identified a NAT of OIP5, a lung cancer oncogene required for chromatin segregation, to be significantly underexpressed, while its sense counterpart, OIP5 mRNA, is significantly overexpressed. We also find that expression of both OIP5 and OIP5-AS1 has a significant impact on 5 year survival. These findings suggest that deregulation of OIP5 through its antisense RNA may represent a novel mechanism regulating tumor phenotypes in NSCLC. Citation Format: Greg L. Stewart, Katey SS Enfield, David A. Rowbotham, Roland Hubaux, Victor Martinez, Stephen Lam, Wan Lam. OIP5-Antisense 1, a long noncoding RNA deregulated in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B26.
Consultees' representations of consultants' psychiatric diagnoses
Authors: A L Callies, M K Popkin, T B Mackenzie, J Mitchell
Journal: American Journal of Psychiatry (1980)

In an attempt to characterize consultees' representations of consultants' psychiatric dagnoses, the authors reviewd the medical records from 190 psychiatric consultations in a general hopsital. Using specific outcome criteria, they rated 50% of representations as concordant and 39% as nonconcordant. Five variable,s icluding the primary medical diagnosis at discharge and the referring service, were significantly related to concordance. Surprisinlgy, concordance was independent of the psychiatric diagnosis, indicating theat consultees did not respond differentially to varying magnitudes and implications of the different disorders. This work raises the question of possible strategies to improve receptivity to psychiatric diagnoses in the consultation setting.
The Bradshaw Lecture ON NERVOUS AFFECTIONS OF THE SIXTH AND SEVENTH DECADES OF LIFE
Authors: J. M. Clarke
Journal: BMJ (1915)

THE sixtlh and seventlh decades of life constitute a period whicll lias certain marked clharacteristics.The age of 45, which Dante fixed as tlle end of thte period of youtlh, miglht lhave been talken as thle lower limiit, but that would involve in most womeen the inclusion of the climacteric, wlhichl I tlhouglht it better to avoid.Maniy nervous diseases run a very long course, and we slhould tllerefore expect to find that the nervous affections of this period will be inade up of some wlich began at an earlier age, and of otlhers, fewer in number, -whose in- cidence is entirely contained witllin it.I do not propose to include miental affections.
Abstract P5-04-06: Analysis of STEAP1 expression as a therapeutic target in breast cancer
Authors: R Aft, C Mudalagiriyappa, S Pillai, M Watson
Journal: Cancer Research (2016)

Abstract Objective: The six transmembrane epithelial antigen of the prostate (STEAP1) is predominantly overexpressed in human prostate cancer. STEAP1 was first identified as a prostate-specific cell-surface antigen and found to be up-regulated in various cancers including lung, bladder, colon, and ovarian with little expression in normal tissue. An anti-STEAP1 monoclonal antibody linked to an antimitotic agent is currently in Phase I clinical trials for prostate cancer patients. Microarray data from our lab suggested that STEAP1 is also highly expressed in human breast cancers and bone marrow disseminated tumor cells. In this study we evaluate expression STEAP1 in primary tumors, and bone marrow (BM) from breast cancer patients. Experimental procedures: RNA was isolated from primary tumor, non-malignant breast tissue and bone marrow (BM) from stage II and III breast cancer patients, healthy volunteers, breast cancer cell lines and BM from patient derived xenographs (PDX). Disseminated tumor cells (DTCs) from patient BM were enriched by microfiltration and analyzed by RNA-in situ hybridization (ISH). STEAP1 RNA expression was analyzed by Nanostring nCounter and qRT-PCR using human specific probes. STEAP1 immunohistochemical (IHC) staining of human tissue was performed using standard protocols. Knockdown of steap1 expression was accomplished using a lentiviral system. Results: STEAP1 mRNA was up-regulated in 77% of tumors (28/36) compared to the corresponding normal tissue. STEAP1 protein was expressed in 100% of tumors (8/8) and was absent in non-malignant breast tissue (7/7) by IHC staining. STEAP1 mRNA was not expressed normal BM, but was detected in 8% (6/74) of BM from patients with early stage breast cancer. STEAP1 expression in the BM was associated with triple negative disease (3/6) and recurrent disease development (4/6, p=.028). STEAP1 expression was observed in individual DTCs isolated from patients BM, while no expression was observed in normal BM. In a PDX model of breast cancer, STEAP1 expression in BM was only observed in mouse who developed metastatic disease associated (7/10, p=.004). Knockdown of STEAP1 in the breast cancer cell line MDA-MB231 cells inhibited cell growth by 80-90%. Conclusion: STEAP1 is expressed in human breast tumors and disseminated tumor cells found in the bone marrow of breast cancer patients. Expression of STEAP1 in the BM is significantly associated with the development of metastatic disease in patients as well as in a mouse model of breast cancer. Our data indicate that STEAP1 could serve as a therapeutic target for the treatment of minimal residual disease in breast cancer. Citation Format: Aft R, Mudalagiriyappa C, Pillai S, Watson M. Analysis of STEAP1 expression as a therapeutic target in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-04-06.
HCP-06PATTERNS OF PHARMACOTHERAPY CHANGES AND SWITCHES SUGGEST UNMET NEED IN US PATIENTS WITH ACROMEGALY
Authors: John Carmichael, Maureen Neary, Eunice Chang, Michael Broder, Dasha Cherepanov, William Ludlam
Journal: Neuro-Oncology (2015)

BACKGROUND: Acromegaly, a slowly progressive disorder due to growth hormone excess, is managed with multiple treatment modalities in clinical practice. About 50% of acromegaly patients require adjuvant therapy after surgery, which may include multiple medications. Guidelines suggest a sequence of medical therapy, but treatment choices are usually individualized and actual treatment practices are unknown. METHODS: This retrospective cohort study used 2 databases (Truven Health Analytics MarketScan; IMS Health PharMetrics) of patients with ≥2 medical claims with acromegaly (ICD-9-CM code 253.0) and ≥1 pharmacotherapy claim during 1/1/2002-12/31/2013. We conducted descriptive analyses for varying patient cohorts to report on pharmacologic switch rates and stops, and subsequent pharmacotherapy among initial switchers who switched after 2007. A switch was an addition or change in pharmacotherapy. RESULTS: Depending on the year, 7.4-10.6% of all pharmacologically treated patients switched to a new treatment and 4.1-9.3% stopped treatment. For all patients who either stopped or switched therapy, 63.6% changed to a different treatment and 36.4% stopped pharmacologic treatment completely. Among patients who switched pharmacotherapy, 23.2% switched to a combination pharmacotherapy, followed by octreotide-LAR (19.1%), lanreotide (17%), cabergoline (16.3%), pegvisomant (14.2%), octreotide-SA (6.7%) and bromocriptine (3.4%). Combination treatments were least likely to end in cessation (10.0%) and treatment with bromocriptine and cabergoline were most likely to end with cessation of all pharmacotherapy (50.6% and 47.4%, respectively). CONCLUSIONS: From 2002-2013, 12.9-17.8% of patients annually either switched pharmacotherapy once or multiple times or stopped treatment altogether, with a greater proportion of these patients switching to a new treatment regimen. This suggests an unmet need for adequate treatment of acromegaly. Many patients who changed initial pharmacotherapy to combination therapy may have switched due to inadequate disease control. Dopamine agonists, generally less efficacious, were more commonly stopped than other pharmacotherapies. The role of radiotherapy and recently approved pasireotide were not examined in these treatment patterns.
Consequences of Increasing Time to Colonoscopy Examination After Positive Result From Fecal Colorectal Cancer Screening Test
Authors: Reinier G.S. Meester, Ann G. Zauber, Chyke A. Doubeni, Christopher D. Jensen, Virginia P. Quinn, Mark Helfand, Jason A. Dominitz, Theodore R. Levin, Douglas A. Corley, Iris Lansdorp-Vogelaar
Journal: Clinical Gastroenterology and Hepatology (2016)
Abstract B18: Targeting histone deacetylase 6 (HDAC6) depresses proliferation and induces caspase-associated cell death in glioblastoma multiforme (GBM) cells and GBM stem cell-like spheroids
Authors: Mohammad Reza Saadatzadeh, Khadijeh Bijangi Vishehsaraei, Haiyan Wang, Aaron Cohen-Gadol, Karen E. Pollok, Ahmad R. Safa
Journal: Cancer Research (2015)

Abstract Glioblastoma multiforme (GBM) comprises the most common and very aggressive form of primary brain tumor with a dismal prognosis and very poor response to the current therapies. HDAC inhibitors (HDACi) are capable of inducing growth arrest and apoptosis in various tumor cell types. HDAC6 is a unique enzyme having two deacetylase domains, and a ubiquitin-binding domain. HDAC6 interacts with a number of proteins in the cytoplasm and is involved in tumorigenesis, cell motility, and metastasis. Significantly, it has been shown that HDAC6 knockout mice are viable. Therefore, in this study, we evaluated HDAC6 as a relevant target for GBM treatment by using a potent HDAC6 inhibitor, CAY 10603. Our data showed that CAY 10603 targets the established GBM cell line U86MG, M-HBT161 early primary cultures, and CD133- and SOX2-positive stem cell-like spheroids. CAY 10603 at 1-5 μM triggered significant inhibition of cell survival and induced apoptotic cell death in GBM cells and GBM spheroids. CAY 10603 reduced cell survival in these cells by 50% (IC50) at 1-3 μM treatment for 48 h. Similarly, CAY 10603 induced significant dose-dependent inhibition of spheroid survival in U87MG and M-HBT161 when the spheroids were grown in a defined GBM stem cell (GSC) growth medium on ultra-low attachment plates for four days. Interestingly, when grown in the same medium but on plates which promote attachment, the spheroids were 3-4 fold more sensitive to CAY 10603, indicating that growth conditions affect the sensitivity of GBM stem cell-like spheroids. Moreover, CAY 10603 triggered cell death in U87MG and M-HBT161 cells as well as CD133/SOX2-expressing spheroids was associated with activation of caspases-3, -6 and -9. Overall, our results show that CAY 10603 robustly inhibits the growth of GBM cells, and is effective in eliminating spheroids that contain GBM cancer stem cells which play a major role in drug resistance and disease recurrence. These results suggest that use of CAY 10603 alone or in combination with other agents may potentially improve the survival of brain tumor patients. Citation Format: Mohammad Reza Saadatzadeh, Khadijeh Bijangi Vishehsaraei, Haiyan Wang, Aaron Cohen-Gadol, Karen E. Pollok, Ahmad R. Safa. Targeting histone deacetylase 6 (HDAC6) depresses proliferation and induces caspase-associated cell death in glioblastoma multiforme (GBM) cells and GBM stem cell-like spheroids. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B18.
Reliability of the Part II Board Certification Examination in Psychiatry: interexaminer consistency
Authors: J F McDermott, P E Tanguay, S C Scheiber, D Juul, J H Shore, G J Tucker, L McCurdy, L C Terr
Journal: American Journal of Psychiatry (1991)

The aim of the study was to examine the reliability (interexaminer consistency) of the American Board of Psychiatry and Neurology (ABPN) Part II (oral) examination in psychiatry.Grades were assigned independently by two examiners who observed the same examination in a 1-year cycle (1,422 candidates, two examinations each). The consistency between these pairs of grades (pass, condition, fail) was analyzed using a weighted kappa statistic.There was perfect agreement between examiners in 67% of examinations, minor disagreement in 26%, and major disagreement in 7% (weighted kappa = 0.54-0.56).The Part II ABPN examination demonstrates fair to good reliability as measured by interexaminer consistency. Development of more explicit grading criteria should further improve examiner agreement in future examinations.