tbuckley/cabot-search huggingface dataset:
Morphogenesis in Animal Tissue Cultures&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Peter J. Gaillard
Journal: JNCI Journal of the National Cancer Institute (1957)

Morphogenesis in Animal Tissue Cultures Get access Peter J. Gaillard Peter J. Gaillard University of Leiden, Leiden, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 4, October 1957, Pages 591–607, https://doi.org/10.1093/jnci/19.4.591 Published: 01 October 1957 Article history Received: 28 May 1957 Published: 01 October 1957
Tumors Associated With Embedded Polymers&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: F. E. Russell, M. H. Simmers, A. E. Hirst, R. H. Pudenz
Journal: JNCI Journal of the National Cancer Institute (1959)

A study was made of the long-term tissue effects of certain polymers when embedded in the subcutaneous tissues of the abdominal wall of rats. Five of the 299 animals that survived 300 days or more developed malignant tumors at the site of the implants. The tumors included 4 spindle-cell sarcomas and 1 undifferentiated sarcoma. A benign fibroma was found about one implant.
Soundings: All change
Authors: Colin Douglas
Journal: BMJ (1999)

I think that I am beginning to lose count. The first was a very long time ago, and I was caught up in it only because, for reasons that seemed good enough at the time, I had taken a year out after the then traditional first year. When I came back they had changed the curriculum.

So the year I joined was the first to test the new arrangements. The anatomists—having endured a cut in the teaching time from 900 to 500 hours—responded robustly, teaching the same old stuff almost twice as fast.

We rose to that challenge, and to similar demands from physiologists and biochemists. The year behind us did less well; what to us was a challenge was to them merely absurd. The course was judged a success, but a few years later the curriculum changed again.

Again our lot was caught. Some resented the loss of an anticipated long summer vacation. I did not mind. Weeks and weeks of general medicine in Kirkcaldy seemed much more fun.

Then things changed again: something to do with integrating clinical and non-clinical subjects. Products of the old system, we had failed to notice the disintegrated nature of our education until it was thus pointed out to us. Happily, most of us seem to have coped anyway. Now our most recent curriculum is in its turn considered obsolete. Too integrated? Or not integrated enough? No matter. It’s going shortly, in favour of something completely different.

A very long time ago an Edinburgh medical student was reproached by the professor of anatomy, one Munro Tertius, the disappointing third generation holder of an apparently hereditary post, for not taking notes in class. The student replied, quite reasonably, that there was no need: his father had left him some perfectly adequate notes from lectures given by the speaker’s grandfather. Curricular stability, it seems, was once valued very highly, at least in Edinburgh.

But the worry now is that—with everything else about medicine changing so fast—what we teach is changing far too slowly. Hospitals shrink. Surgery fades. New technologies breed faster and faster. Medicine deinstitutionalises itself. Distance learning burgeons. So how do yesterday’s doctors prepare tomorrow’s for all that?

The curriculum is long, the art now almost too brief to be captured by it. Time not for a new curriculum, but for a permanent curricular revolution. Any volunteers?
Expression of mRNA for Transforming Growth Factors-α and -β and Secretion of Transforming Growth Factor-β by Renal Cell Carcinoma Cell Lines
Authors: E R Sargent, L G Gomella, T P Wade, M W Ewing, A Kasid, W M Linehan
Journal: Cancer Communications (1989)

Transforming growth factors (TGFs)-alpha and -beta are regulatory polypeptides that reversibly confer a transformed phenotype upon normal cultured fibroblasts. TGF-alpha is synthesized primarily by malignant cells and shares many properties with the tissue mitogen, epidermal growth factor (EGF). The expression of TGF-beta mRNA has been demonstrated in a variety of normal and malignant cell types, some of which secrete the mature protein in an inactive form. To investigate the role of TGFs in human renal cell carcinoma (RCC), we used two renal tumor-derived cell lines and one established RCC cell line for analysis of TGF-alpha and TGF-beta mRNA production and for evaluation of TGF-beta protein secretion. By northern blot hybridization, all three RCC cell lines expressed TGF-alpha and -beta mRNA. In addition, TGF-beta activity was found in the conditioned medium from these cells. The secreted TGF-beta protein, however, displayed biological activity only after activation by acid-treatment. These data demonstrate the constitutive expression of TGF-alpha and -beta mRNA by RCC cell lines and, also, the secretion by this tumor of endogenous TGF-beta protein in a latent form.
Abstract 239: Selective Class I and II Histone Deacetylation Inhibitors Alter Stability of HDAC-Corepressor Complexes
Authors: Hsiao C Wang, Lillianne G Harris, James C Chou, Santhosh Mani, Donald Menick
Journal: Circulation Research (2014)

Introduction: Alterations in expression and activity of different genes have been implicated in the pathogenesis of heart failure. Our lab has shown that HDAC-repressor complexes play a critical role in the upregulation Sodium Calcium Exchanger ( Ncx1) and HDAC inhibition causes changes that attenuated cardiac remodeling during cardiac hypertrophy and heart failure. Thus, treatment with HDAC inhibitors has been proposed as a potential strategy for treatment of cardiac hypertrophy and heart failure. HDAC inhibitors repress deacetylase activity but we propose that they also affect HDAC confirmation and interaction with other protein factors. We hypothesize that HDAC inhibitors affect the stability of the co-repressor complex with specific transcription factors and that this effect is dependent on the transcription factor. Results: Inhibition of HDACs in adult cardiomyocytes results in the greater stabilization of HDACs with co-repressor molecules that were recruited to the NCX1 promoter through Nkx2.5 transcription factor. HDAC class I specific inhibitor, MS 275 demonstrated stronger association between HDACs and co-repressors while other Class I inhibitors, PD106 and BML 210 failed on showing this phenomenal. The results suggested that class I HDACs inhibitors may affect formations of HDAC-complex via alternated active site interactions other than chelating with zinc binding domain. These results compliment ChIP experiments which also demonstrate the different recruitments of Sin3a at the proximal promoter of NCX1. In vivo analysis on HDAC5 knockout mice reveal that the Sin3a-HDAC1/2 repressor complex is not recruited to the Ncx1 promoter in the absence of HDAC5, indicating not only Class I HDAC but also Class II HDACs play an important role on HDAC-complex formation. Conclusions: This work gives insight into part of the molecular mechanism of how HDAC inhibitors can affect the stability of the HDAC co-repressor complex in cardiac hypertrophy and heart failure. In addition, we demonstrated the Class IIa HDACs are required for the recruitment of the Sin3a/HDAC1/2 co-repressor complex to specific transcription factors on the target promoter.
Abstract P6-12-13: Awareness and acceptability of skin application of preventive medications for breast cancer
Authors: LC Karavites, S Allu, SA Khan, K Kaiser
Journal: Cancer Research (2016)

Abstract OBJECTIVE: To better understand women's knowledge and perceptions of breast cancer prevention medications and determine if a topical administration of these medications would increase acceptability. METHODS: Focus groups were conducted with healthy women identified through the breast center of a single institution. An experienced moderator led participants through a discussion of breast cancer risk perceptions, knowledge of and concerns about risk reduction medications, and their views of a skin application of risk reducing medication. Participants provided sociodemographic information, breast cancer risk factors, and prior physician recommendations to take risk-reducing medicines. Trained research personnel examined all qualitative results systematically. Participants' breast cancer risk was estimated using the Gail Model. RESULTS: Four focus groups (N=32) were conducted. Most participants had at least a college degree (78.2%) and were of either European (50%) or African ancestry (31%). The majority (72%) were at elevated risk for breast cancer, just over half of these women perceived themselves to be at higher than average risk. Only 19% of participants had prior knowledge of preventive medications. Women who perceived themselves to be at high risk were more likely to know about preventive medications than those who did not, 38% vs 0% respectively. Over 90% of the focus group participants stated that they would prefer a topical application of a preventive medication to a pill if their physician advised them to take preventive medication. CONCLUSION: Awareness of preventive medications was low even in a highly educated sample of high-risk women. If given a choice in the route of administration of chemoprevention, nine out of ten women preferred a gel to a pill. Future work should focus on demonstrating a reduction in side effects of topical over oral medications and raising awareness of chemopreventive options for breast cancer to increase acceptance of preventive medications. Citation Format: Karavites LC, Allu S, Khan SA, Kaiser K. Awareness and acceptability of skin application of preventive medications for 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 P6-12-13.
Barrett's Esophagus
Authors: Prateek Sharma
Journal: New England Journal of Medicine (2009)

A 56-year-old obese man with long-standing gastroesophageal reflux who recently received a diagnosis of Barrett's esophagus presents for a follow-up visit. He has been taking omeprazole at a dose of 20 mg twice daily and currently has no symptoms of reflux. He has no dysphagia or weight loss. Endoscopic and histopathological examinations show a 4-cm segment of Barrett's esophagus without dysplasia. How should Barrett's esophagus be managed?
Twilight: filter the blue light of your device and sleep better
Authors: Arthur Henrique Bossi, James Hopker
Journal: British Journal of Sports Medicine (2016)

Twilight

Health and fitness.

Android (V2.2 or above).

Free; ‘Pro’ version available for €1.99/£1.99/US$1.99.

The Twilight app was created to help people mitigate sleep perturbations arising from the usage of self-illuminating electronic devices (eg, mobile phones and tablets) prior to sleeping.1 Blue light in the range of wavelengths 446–477 nm has been identified as the most potent light stimulus that suppresses melatonin production,2 a hormone that plays a major role in the regulation of sleep and wake cycles.3 Accordingly, Twilight filters the blue light emitted from mobile devices and protects the eyes with a soft red pellicle, potentially helping the user to fall asleep earlier and sleep better.1 ,4 ,5 On the basis of the user's local geographic coordinates, which are taken by …
Emergency Health Planning
Authors: A C HARDMAN
Journal: JAMA (1963)

F OLLOWING the transfer, in 1951, of the re- sponsibility for civil defence from the Department of National Defence to the Department of National Health and Welfare, a civil defence health planning group was formed within the Health Branch.This group studied the bealth problems associated with the major threat of that time, namely, the relatively small atomic bomb delivered by manned aircraft.In these studies, problems were referred to working parties selected from authorities on the particular subject.Information obtained by this and other means was provided to the health professions by means of articles, pamphlets and manuals and through courses, conferences and institutes held across Canada.The development of the large thermonuclear weapon in 1954, and of new delivery systems, caused a major revision of Civil Defence Health Services' policies and programs.This was followed in 1959 by a major reorganization of civil defence in which the Civil Defence Health Services became the Emergency Health Services Division of the Health Directorate of the Department of National Health and Welfare.During this period, emergency health planning by provincial and municipal governments across Canada received widely varying degrees of emphasis, with few concrete achievements.
Abstract P3-01-14: A nomogram to predict the likelihood of axillary non-sentinel lymph node metastases in sentinel lymph node positive primary breast cancer patients
Authors: AD Hartkopf, SY Brucker, G Helms, M Henzel, M Hahn, M Wallwiener, B Schoenfisch, F-A Taran, TN Fehm
Journal: Cancer Research (2016)

Abstract Background: Completion of axillary lymph node dissection (ALND) was long lasting standard in patients with non-metastatic primary breast cancer (PBC) and axillary sentinel lymph node (SLN) involvement. However, this approach is currently questioned since recent prospective trials have found that some SLN-positive women with PBC might not benefit from subsequent ALND. Nomograms that estimate the probability of further non-sentinel lymph node (NSLN) metastases could guide clinical decisions. Methods: We compared the predictability of three different nomograms (MSKCC, Stanford University, Cambridge) on the NSLN status with an own logistic regression model in a training and validation set. SLN-positive women who underwent primary surgery including ALND at Tuebingen University, Germany, between 06/2005 - 12/2009 (training set) and 01/2010 - 02/2012 (validation set) were available for this analysis. The area under the receiver operating characteristics (ROC) curve was calculated for each nomogram. Results: 295 and 175 patients were included into the training and validation set, respectively. Of these 118 (40%) and 57 (33%) patients were NSLN-positive. Variables within our model were tumor size, proportion of positive SLNs, size of SLN metastases, lymphangiosis carcinomatosa, multicentricity and extracapsular invasion. The respective area under the ROC curve values for the MSKCC / Stanford University / Cambridge / own regression model were 0.73 / 0.70 / 0.63 / 0.75 in the training set and 0.73 / 0.66 / 0.52 / 0.73 in the validation set. Conclusion: The predictability of our logistic regression model was comparable to the MSKCC nomogram and superior to the Stanford University and Cambridge nomogram. Although a training and a validation set was used, further testing on an independent patient population is warranted. Citation Format: Hartkopf AD, Brucker SY, Helms G, Henzel M, Hahn M, Wallwiener M, Schoenfisch B, Taran F-A, Fehm TN. A nomogram to predict the likelihood of axillary non-sentinel lymph node metastases in sentinel lymph node positive primary breast cancer patients. [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 P3-01-14.
Long-Term Air Pollution and Traffic Noise Exposures and Mild Cognitive Impairment in Older Adults: A Cross-Sectional Analysis of the Heinz Nixdorf Recall Study
Authors: Lilian Tzivian, Martha Dlugaj, Angela Winkler, Gudrun Weinmayr, Frauke Hennig, Kateryna B. Fuks, Mohammad Vossoughi, Tamara Schikowski, Christian Weimar, Raimund Erbel, Karl-Heinz Jöckel, Susanne Moebus, Barbara Hoffmann
Journal: Environmental Health Perspectives (2016)

Background:Mild cognitive impairment (MCI) describes the intermediate state between normal cognitive aging and dementia. Adverse effects of air pollution (AP) on cognitive functions have been proposed, but investigations of simultaneous exposure to noise are scarce.Objectives:We analyzed the cross-sectional associations of long-term exposure to AP and traffic noise with overall MCI and amnestic (aMCI) and nonamnestic (naMCI) MCI.Methods:At the second examination of the population-based Heinz Nixdorf Recall study, cognitive assessment was completed in 4,086 participants who were 50–80 years old. Of these, 592 participants were diagnosed as having MCI (aMCI, n = 309; naMCI, n = 283) according to previously published criteria using five neuropsychological subtests. We assessed long-term residential concentrations for size-fractioned particulate matter (PM) and nitrogen oxides with land use regression, and for traffic noise [weighted 24-hr (LDEN) and night-time (LNIGHT) means]. Logistic regression models adjusted for individual risk factors were calculated to estimate the association of environmental exposures with MCI in single- and two-exposure models.Results:Most air pollutants and traffic noise were associated with overall MCI and aMCI. For example, an interquartile range increase in PM2.5 and a 10 A-weighted decibel [dB(A)] increase in LDEN were associated with overall MCI as follows [odds ratio (95% confidence interval)]: 1.16 (1.05, 1.27) and 1.40 (1.03, 1.91), respectively, and with aMCI as follows: 1.22 (1.08, 1.38) and 1.53 (1.05, 2.24), respectively. In two-exposure models, AP and noise associations were attenuated [e.g., for aMCI, PM2.5 1.13 (0.98, 1.30) and LDEN 1.46 (1.11, 1.92)].Conclusions:Long-term exposures to air pollution and traffic noise were positively associated with MCI, mainly with the amnestic subtype.Citation:Tzivian L, Dlugaj M, Winkler A, Weinmayr G, Hennig F, Fuks KB, Vossoughi M, Schikowski T, Weimar C, Erbel R, Jöckel KH, Moebus S, Hoffmann B, on behalf of the Heinz Nixdorf Recall study Investigative Group. 2016. Long-term air pollution and traffic noise exposures and mild cognitive impairment in older adults: a cross-sectional analysis of the Heinz Nixdorf Recall Study. Environ Health Perspect 124:1361–1368; http://dx.doi.org/10.1289/ehp.1509824
Abstract PL2: Clonal Dynamics and Breast Cancer Subtypes
Authors: S Aparicio
Journal: Cancer Research (2016)

Abstract Breast cancers exhibit inter-patient and intra-tumoural genomic variability which underpins our understanding of intrinsic drivers of the disease. The advent of next generation sequencing methods and informatics approaches has redefined the landscape of primary breast cancer subtypes into many more molecularly defined patient subgroups than had been previously appreciated, thus redefining our understanding of inter-patient variation. These studies have implications for the understanding of driver mutation context in primary cancers and should pattern future clinical and molecular studies of primary breast cancers. Closely linked to inter-patient genomic variability is the notion that most cancers are ecosystems of evolving cellular clones has implications for biological understanding and clinical application. The evolution of clonal composition has particular significance when evidence of positive or negative selection can be associated with the clonal genotype or epigenotype. Over the last 5 years next generation sequencing of tumours and methods for single cell analysis have opened up this approach for solid epithelial malignancies. I will discuss the implications of clonal evolution for cancer medicine and biological studies of cancer with reference to breast cancers. We have developed informatics approaches to population level clonal analysis and extended these to single cell measurements of genotypes. I shall discuss our more recent data from single cell sequencing and clonal analysis applied to clonal evolution of patient derived tumour xenografts, to illustrate the impact of clonal evolution on biological studies of breast cancer in model systems. Citation Format: Aparicio S. Clonal Dynamics and Breast Cancer Subtypes. [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 PL2.
Highlights from the 26th ECCMID
Authors: Marco De Ambrogi, John McConnell, Ammara Mushtaq
Journal: The Lancet Infectious Diseases (2016)

The 26th running of the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) held this year in Amsterdam, Netherlands, attracted 11 350 participants from 123 countries. Marco De Ambrogi, John McConnell, and Ammara Mushtaq report on the meeting highlights.
Abstract P3-04-03: Investigating the therapeutic use of estrogen receptor β agonists in breast cancer
Authors: C Samayoa, NK Krishnegowda, R Vadlamudi, RR Tekmal
Journal: Cancer Research (2016)

Abstract In breast cancer, estrogen receptor status reflects the biology of the tumor and is used to determine the likelihood of responding to endocrine therapy. 70% of all breast cancers express Estrogen Receptor α, which is indicative of estrogen dependence for growth. Current therapies aim to lower estrogen levels, or inhibit estrogen receptor signaling to ultimately prevent recurrence. However, only two-thirds of ERα-positive respond to endocrine therapy. The Estrogen Receptors are ligand-activated transcription factors with similar structures that slightly differ in their DNA binding sites and ligand binding domains. Estrogen Receptor α has been shown to induce the proliferation of mammary gland cells, whereas Estrogen Receptor β exhibits tumor suppressive properties. The objective of this study was to investigate the utility of selective ERβ agonists as a treatment for breast cancer. Using different breast cancer models, we investigated the effects of ERβ agonist treatment on growth, migration, apoptosis, cell cycle distribution and gene expression. In this study, we demonstrate that treatment with ERβ agonist results in inhibition of cell growth and migration. Additionally, treatment also impacts cell cycle distribution and affects key proteins involved in cell cycle regulation. We also demonstrate an increase in ERβ mRNA and protein levels upon treatment. This shift in the ERβ to ERα ratio, represents a viable targeting strategy in the treatment of breast cancer. To determine if our finding translate in-vivo, we employed xenograft and syngeneic mouse models. Our in-vivo studies demonstrated reduced tumor volumes in mice treated with ERβ agonists in combination with conventional therapy, confirming the growth inhibitory activity of ERβ agonists. Selective activation of ERβ, through the use of ERβ agonists has enabled us to exploit its tumor suppressive function and investigate the utility as a treatment for breast cancer. This study suggest that activation of ERβ signaling is a valuable strategy to inhibit breast cancer growth and progression. Citation Format: Samayoa C, Krishnegowda NK, Vadlamudi R, Tekmal RR. Investigating the therapeutic use of estrogen receptor β agonists 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 P3-04-03.