tbuckley/cabot-search huggingface dataset:
RT-27 * THE ROLE OF SYSTEMIC THERAPY AFTER STEREOTACTIC RADIOSURGERY FOR SYNCHRONOUS BRAIN METASTASES FROM LUNG CANCER
Authors: S. Patel, W. F. Mourad, R. Young, R. Kabarriti, R. Patel, T. Santiago, R. Yaparpalvi, L. Hong, P. LaSala, S. Kalnicki, M. K. Garg
Journal: Neuro-Oncology (2014)

PURPOSE: To assess our experience with stereotactic radiosurgery (SRS) in treating synchronous brain metastases from lung cancer primaries and to analyze the prognostic significance of post-SRS systemic therapy (PSST). MATERIALS AND METHODS: In this single-institution retrospective study, we analyzed 51 patients diagnosed with lung cancer and synchronous brain metastases (CNS disease found at onset or within 2 months of lung cancer diagnosis) who underwent LINAC-based SRS between 2007 and 2013. SRS was delivered to one lesion (range 1-5) with a median prescription dose and treatment volume of 21Gy and 1.5cc, respectively. Patients underwent metastectomy (25%), whole brain radiation (WBRT) (10%), or both (6%) prior to SRS while 52% received PSST. At time of SRS, 52% of patients had only pulmonary disease while 48% had distant disease. The SRS-PSST interval (SPI) was examined. Cox regression analyses were performed. RESULTS: At a median follow-up of 6 months (1-59), the median survival was 6.2 months and the actuarial overall survival at 3, 6, 12, and 36 months was 71%, 51%, 29%, and 7%, respectively. Distant disease negatively predicted for survival (HR 2.2, 95% CI 1.0-4.6, p = 0.039) while the addition of PSST positively predicted for survival (HR 0.3, 95% CI 0.2-0.7, p = 0.003). Age, gender, race, metastectomy or WBRT prior to SRS, number of lesions, lesion size, and prescription dose were not significant. In patients receiving PSST, longer PSST duration and SPI did not impact survival. CONCLUSION: Our results suggest the prognostic significance of PSST. While our previous work revealed longer duration of PSST and SPI >30 days to predict for improved survival, this was not found in this subgroup of patients. This suggests that PSST has a differential impact on patients with synchronous metastases. Further investigation is warranted to elucidate the role and optimal timing of PSST in these patients.
The Clinical Significance of Data Accumulated in the Medical Care of Young Women
Authors: Harriet L. Hardy
Journal: New England Journal of Medicine (1945)

CLINICIANS have not shown great interest in the study of the so-called "normal." The physiologists have made useful contributions, but these have not, for the most part, reached the clinician in such a way that he is led to apply the knowledge thus acquired. A review of the literature since 1918 reveals less than forty references dealing with the subject of normal physical findings as related to clinical medicine. A few of these deserve listing.1 2 3 4 5 6 The Selective Service findings reported and publicized by Rowntree7 have brought up many questions about supposedly normal and supposedly healthy men. Members of the Grant . . .
IS AVAILABILITY OF MR ENTEROGRAPHY (MRE) REDUCING AVOIDABLE USE OF IONISING RADIATION IN DIAGNOSTIC IMAGING FOR CROHN'S DISEASE?
Authors: A E Smyth, D J Gibson, D J Murphy, D Keegan, G Cullen, H E Mulcahy, D Malone, G A Doherty
Journal: Gut (2013)

<h3>Introduction</h3> MRE has been increasingly adopted as the imaging modality of choice for patients with small bowel Crohn9s disease, replacing barium studies and CT. MRE has similar sensitivity to CT for detection of small bowel inflammatory changes but has the advantage of no exposure to ionising radiation. <h3>Aims/Background</h3> We aimed to evaluate whether the availability of MRE has diminished or eliminated avoidable radiation exposure related to diagnostic imaging in this patient group. <h3>Method</h3> Retrospective analysis of a database of 3000 patients with IBD in a large tertiary referral hospital was performed. All patients diagnosed with Crohn9s disease during the period of 01-01-2009 until 15-10-2012 were identified. A review was performed of all abdominal imaging done at the study centre–MRE, abdominal CT and barium small bowel studies. <h3>Results</h3> 122 patients had a new diagnosis of Crohn9s disease. 58 (47.5%) were female. Median age at diagnosis was 28 years (IQR 23–40). A total of 62 MRE studies were performed in 52 patients (42.6%). 26 patients (21%) had a barium small bowel examination. A total of 83 abdominal CT studies were performed in 52 patients (42.6%). 35 (42%) of these were performed as an emergency investigation. 18 patients had 2 or more abdominal CT studies performed (range 2–6). 55 patients (45%) had an abdominal CT or barium examination performed in a non-emergency setting. <h3>Conclusion</h3> This study shows that there is still significant use of ionising radiation, sometimes performed repeatedly, in a non-emergency setting. 45% of this young patient cohort received avoidable radiation exposure related to diagnostic imaging.
FRI0314 Aetiology of experimentally induced osteoarthritis of the knee; biomechanical or biochemical factors?
Authors: K. Wiegant, M. Beekhuizen, S.C. Mastbergen, A.D. Barten-van Rijbroek, L.B. Creemers, D.B. Saris, F.P. Lafeber
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> At the moment, osteoarthritis (OA) is seen as a multifactorial disease, caused by a combination of i.a. genetics, overloading, obesity and trauma in the past. Disturbance of joint homeostasis, due to several risk factors, can also cause OA<sup>1</sup>. In the present study we investigated the role of biomechanical loading and biochemical joint homeostasis in the development of osteoarthritis, in an experimental caprine model of joint damage. <h3>Objectives</h3> Is the development of experimentally induced OA more due to changed biomechanics or is it due to a changed joint homeostasis? <h3>Methods</h3> In nine skeletally mature female milk goats, cartilage damage was introduced in the right stifle joint according to the Groove model<sup>2</sup>. Grooves were made with a K-wire with a bend tip, only on the medial femoral condyle and maximally 0.5mm deep; preventing the subchondral plate from damage. The left stifle joint served as a control. After 20 weeks the goats were sacrificed and the cartilage and synovial tissue was analyzed on macroscopical, histological (both OARSI goat score) and biochemical (proteoglycan (PG) turnover) OA characteristics. <h3>Results</h3> Macroscopic analysis showed a significant increase in the OARSI goat cartilage score for both the femoral and tibial experimental medial compartment compared to control (femur and tibia; +225% p&lt;0.001 and +42.9% p&lt;0.04 respectively). No effect on the ungrooved lateral compartment was seen. The histological analysis of the cartilage corroborated these results. A significant increase in the OARSI score for the experimental medial compartment (+225% p&lt;0.001 and +81,7% p&lt;0.006, respectively for femur and tibia) was seen. Biochemical analysis showed a decreased PG content in the medial experimental compartment compared to control (femur -12.1% p=0.038 and tibia -7.3% p=0.031). There was a slight increase in synovial inflammation in the experimental joint (p&lt;0.003). For all previous mentioned analyses, no changes in the experimental lateral compartment or the control joint were found. <h3>Conclusions</h3> The present study shows clearly that the development of joint damage is much more dependent on the biomechanical component, since all detectable damage is in the medial compartment. Although joint homeostasis is disturbed, indicated by moderate synovial inflammation, this did not lead to generalised OA in this time period. <h3>References</h3> Abramson et al. Arthritis Res Ther. 2009. Mastbergen et al. Osteoarthritis and Cartilage 2006. <h3>Disclosure of Interest</h3> None Declared
P120 Ambient exposure to diesel traffic particles and cardio-respiratory outcomes in healthy and in COPD subjects: ‘Oxford Street 2’
Authors: R Sinharay, B Barratt, JP Rocha, W Meesang, P Collins, F Kelly, KF Chung, P Cullinan
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Chamber studies using reconstituted diesel exhaust with healthy volunteers have shown enhanced lung inflammation resulting in vascular dysfunction. We hypothesised that inhalation of ambient levels of diesel emissions (DE) in patients with COPD or ischaemic heart disease (IHD) would induce oxidative stress with an acute airway inflammatory response and up-regulation of systemic inflammatory responses, reflected in abnormal cardiovascular physiology. <h3>Methods</h3> Using a randomised, cross-over design, healthy non-smoking volunteers (n = 40) and patients with Stage 2 COPD (n = 40) are invited to walk in Oxford Street (only diesel traffic) and, on a separate occasion 3–8 weeks later, in Hyde Park, London. Personal particulate and gaseous exposures are measured in real time. Following baseline measurements, participants walk for two hours in either exposure location; a series of cardio-respiratory measurements are performed at intervals during and after each exposure. Here we report lung function and arterial stiffness measurements in the first 20 volunteers (10 with COPD). <h3>Findings</h3> Compared to Hyde Park, exposures in Oxford Street had higher levels of black carbon (7.5μm/m<sup>3</sup><i>vs</i>. 1.2μm/m<sup>3</sup>, p &lt; 0.001), and ultrafine particle counts (28692/cm<sup>3</sup> vs. 4989/cm<sup>3</sup>,p &lt; 0.001). In comparison with Hyde Park, healthy volunteers had a mean fall in FEV<sub>1</sub> from baseline of -1.9% (p = 0.04) one hour after arrival in Oxford street; at 22 hours they had a mean decline of -8% (p = 0.03). In contrast, there were no significant differences in FEV<sub>1 </sub>responses in volunteers with COPD, though there was a mean drop in FVC of -8% (p = 0.03) two hours after the start of exposure in Oxford street compared to Hyde Park. We recorded no changes in arterial stiffness in either group for either exposure site. <h3>Conclusions</h3> These early findings suggest that the observations made in healthy volunteers from chamber studies can be replicated in ambient conditions. The apparent lack of any respiratory response in patients with COPD may reflect their up-regulated baseline inflammatory state, or systematic differences in the exposure differential between the two sites. We continue to recruit volunteers; further measurements including markers of oxidative stress in sputum, serum, and small airways impedance are under way. Funded by the British Heart Foundation.
Vitamin A, beta-Carotene, and the Risk of Cancer
Authors: S. GRAHAM
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Vitamin A, β-Carotene, and the Risk of Cancer Get access SAXON GRAHAM SAXON GRAHAM Department of Social and Preventive MedicineState University of New York at Buffalo, 2211 Main Street Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 2, 16 March 1988, Page 76, https://doi.org/10.1093/jnci/80.2.76 Published: 16 March 1988
Cancer Survivors Meet Nationally With Growing Agenda
Authors: M. Hampton
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Cancer Survivors Meet Nationally With Growing Agenda Get access Maree Hampton Maree Hampton Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 2, 18 January 1989, Pages 95–96, https://doi.org/10.1093/jnci/81.2.95 Published: 18 January 1989
TrkA Overexpression Enhances Growth and Metastasis of Breast Cancer Cells, and Ku86 Is Crucial for TrkA Overexpression-Induced Breast Cancer Cell Invasion.
Authors: C. Lagadec, S. Meignan, C. Tastet, E. Com, H. Hondermarck, X. LeBourhis
Journal: Cancer Research (2009)

Abstract The Trk family of neurotrophin tyrosine kinase receptors is emerging as an important player in carcinogenic progression in non-neuronal tissues. Here, we show that breast tumors present high levels of TrkA and phospho-TrkA compared to normal breast tissues. To further evaluate the precise functions of TrkA overexpression in breast cancer development, we have performed a series of biological tests using breast cancer cells that stably overexpress TrkA. We show that (1) TrkA overexpression promoted cell growth, migration and invasion in vitro; (2) overexpression of TrkA per se conferred constitutive activation of its tyrosine kinase activity; (3) signal pathways including PI3K-Akt and ERK/p38 MAP kinases were activated by TrkA overexpression and were required for the maintenance of a more aggressive cellular phenotype; and (4) TrkA overexpression enhanced tumor growth, angiogenesis and metastasis of xenografted breast cancer cells in immunodeficient mice. Moreover, recovered metastatic cells from the lungs exhibited enhanced anoikis resistance that was abolished by the pharmacological inhibitor K252a, suggesting that TrkA-promoted breast tumor metastasis could be mediated at least in part by enhancing anoikis resistance. Together, these results provide the first direct evidence that TrkA overexpression enhances the tumorigenic properties of breast cancer cells and point to TrkA as a potential target in breast cancer therapy.In a second step, we used a proteomic-based approach to identify proteins involved in TrkA overexpression-stimulated invasion of MDA-MB-231 breast cancer cells. Proteins from control and TrkA overexpressing cells were separated using a cup-loading two-dimensional electrophoresis system before MALDI and LC-MS/MS mass spectrometry analysis. Among several putative modified proteins, Ku86 was found to be the major protein which was increased in TrkA overexpressing cells. Moreover, Ku86 was co-immunoprecipitated with TrkA and its level at the cell surface was increased in TrkA overexpressing cells. Interestingly, inhibition with small-interfering RNA and neutralizing antibodies showed that Ku86 was required for TrkA-stimulated cell invasion. Together, these data allowed the identification of Ku86 as a new player involved in metastasis of breast cancer cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4169.
Abstract 4364: S1P generated by SphK1 is important not only for primary tumor growth but also for tumor-induced hemangiogenesis and lymphangiogenesis
Authors: Masayuki Nagahashi, Subramaniam Ramachandran, Eugene Y. Kim, Jeremy C. Allegood, Omar M. Rashid, Akimitsu Yamada, Renping Zhao, Sheldon Milstien, Huiping Zhou, Sarah Spiegel, Kazuaki Takabe
Journal: Cancer Research (2012)

Abstract INTRODUCTION: Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, regulates many cellular processes important for breast cancer progression. The aim of this study is to investigate a role for S1P produced by sphingosine kinase 1 (SphK1) in breast cancer progression and tumor-induced hemangiogenesis and lymphangiogenesis. METHODS: An isozyme-specific inhibitor of SphK1 (SK1-I) was used. Tumor burden were quantified using an in vivo imaging system (IVIS 2000). S1P and SK1-I levels were measured by LC-ESI-MS/MS. Hemangiogenesis and lymphangiogenesis are determined by morphological analysis of microvessel density as well as by flow cytometric analysis of endothelial cells. RESULTS: A significant dose dependent effect of SK1-I on inhibition of 4T1-luc2 murine breast cancer cell growth was observed. We confirmed that SK1-I decreased the enzymatic activity of SphK1 and that downregulation of SphK1 with specific siRNA also suppressed growth of these cells. We found that S1P levels increased in the tumor and in the circulation after orthotopic implantation of 4T1-luc2 cells. Similarly, serum S1P levels were significantly elevated in stage IIIA breast cancer patients who have lymph node metastases, compared to age/ethnicity-matched healthy volunteers. SK1-I blocked serum S1P increases in in vivo model and reduced lymph node and lung metastases and overall tumor burden in vivo as well. Importantly, SK1-I also decreased hem- and lymphangiogenesis not only in the primary tumor, but also in lymph nodes, the host tumor microenvironment. Whereas supernatants from 4T1-luc2 cells significantly stimulated tube formation of HUVECs and HLECs, shRNA knockdown of SphK1 markedly reduced them, indicating that S1P produced by SphK1 in 4T1-luc2 breast cancer cells is an important contributor to hem- and lymphangiogenesis. CONCLUSIONS: S1P generated by SphK1 is important for tumor progression, tumor-induced hemangiogenesis and lymphangiogenesis, and lymph node metastais. Therefore targeting SphK1 and its product S1P would be a multi-pronged attack against breast cancer. This work was supported by Sumitomo Life Social Welfare Services Foundation grant to MN, NIH (K12HD055881) and Susan G. Komen for the Cure (KG090510) to KT, and NCI (R01CA61774) to SS. 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 4364. doi:1538-7445.AM2012-4364
Assessment of the ThinPrep method for endoscopic ultrasound-guided fine needle aspirates
Authors: Ishida Yusuke, Okabe Yoshinobu, Taira Tomoki, Yamaguchi Tomohiko, Kawahara Akihiko, Yasumoto Makiko, Kaji Ryohei, Sugiyama Gen, Kitasato Yuhei, Kage Masayoshi, Kinoshita Hisafumi, Tsuruta Osamu, Sata Michio
Journal: Endoscopy (2011)

Background and Aim: The ThinPrep method, one of the liquid-based methods of cytologic preparation is often used for gynecologic samples, but there are few studies about pancreatic samples obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The objective of this study was to compare the usefulness of the ThinPrep method versus conventional smear methods in pancreatic samples obtained by EUS-FNA.
P374Expression pattern of sarco (endo) plasmic reticulum calcium atpases (SERCA) isoforms in normal and diseased mouse cardiovascular tissues
Authors: K Blirando, L Lipskaia, Z Keuylian, C Rouxel, R Blaise, S Adnot, RJ Hajjar, ER Chemaly, I Limon, R Bobe
Journal: Cardiovascular Research (2014)

The sarco(endo) plasmic reticulum Ca2+ ATPases (SERCA) system is a key regulator of calcium cycling and signaling in cardiac and vascular myocytes and is composed of several isoforms. We aimed to characterize 1) the expression of the different SERCA isoforms in normal mouse cardiovascular tissues and 2) the modulation of the SERCA isoform system during cardiovascular pathologies (heart failure and/or atherosclerosis). Five SERCA isoforms - 2a, 2b, 3a, 3b and 3c were detected by RT-PCR and immunoblot in normal mouse heart and thoracic aorta. Absolute mRNA quantification (Table) confirmed that SERCA2a was the predominant isoform in the heart (∼99% of total SERCA mRNA) whereas the ubiquitous isoform SERCA2b represents less than ∼0.1%. Within cardiomyocytes (CM), SERCA2a and 2b were co-localized in the longitudinal SR, whereas SERCA3b was located at the junctional reticulum. In the aorta, SERCA2a accounted for ∼86.0% and SERCA2b for ∼7%. Among SERCA3 isoforms (3a, 3b and 3c), SERCA3b was the most expressed (∼6.5%) and was predominantly found in endothelial and vascular smooth muscle cells (VSMC), together with SERCA2a and 2b. In failing CM the SERCA2a expression was 2-fold down-regulated (from 9.65 to 5.01 pg/10 ng of total mRNA). Furthermore, both SERCA2a and SERCA2b were re-localized from longitudinal to junctional SR. A strong down-regulation of SERCA2a was also observed in atherosclerotic vessels (from 0.27 to 0.13 pg/10 ng of total mRNA) containing mainly synthetic VSMC; the proportion of both SERCA2b and SERCA3b increased to reach 8% and 7% respectively. In summary, we established that 1) the overall expression of SERCA mRNA is ∼ 50 fold higher in the heart compared to vascular tissues; 2) although several SERCA isoforms are expressed in cardiovascular tissues, SERCA2a is the major isoform in both cardiac and vascular myocytes; 3) nearly half the amount of SERCA2a mRNA is measured in both failing cardiomyocytes and synthetic VSMCs compared to healthy tissues. Together with the evidence of SERCA2a delocalization from longitudinal reticulum in hypertrophied cardiomyocytes, our study prove that SERCA2a is the principal regulator of excitation-contraction coupling in both CMs and contractile VSMCs and also supports a dynamic and integrated regulation of the SERCA isoform system, which deserves further studies.
Lessons from US reviews show impartiality is needed
Authors: C. J. Baines
Journal: BMJ (2011)

The fate of previous independent breast screening reviews, such as the 1997 US National Institutes of Health Consensus Development Conference and the 2009 United States Preventive Services Task Force,1 2 offers a warning for the so called UK independent review.3 Whatever its conclusions, they will be criticised vociferously.4 Unfortunately, the …
Errors in meta‐analysis on prevalence of nonalcoholic fatty liver disease
Authors: Michael Roerecke, Jürgen Rehm, Manuela Neuman
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the meta‐analysis on global prevalence of nonalcoholic fatty liver disease (NAFLD) by Younossi et al.1 published in hepatology. We commend the authors for undertaking such a task given the fractured state of the literature. However, their selection of studies for the meta‐analysis seems to be incorrect. Specifically, Fig. 3E, which depicts NAFLD prevalence in North America based on noninvasive imaging, includes data from 13 published articles. Nine of these studies are from the same cohort (Third National Health and Nutrition Examination Survey); however, only one of these should have been included.2 Furthermore, the study by Church et al.3 contained participants selected by nine categories of body mass index and fitness with an equal number of participants per category and cannot be used to calculate prevalence of NAFLD, which is strongly correlated with body mass index. In fact, any samples where the sampling frame was based on risk factors correlated with the outcome (NAFLD), such as body mass index, diabetes mellitus, hypertension, dyslipidemia, or other components of the metabolic syndrome, should not be combined with population‐based samples in a meta‐analysis because clinical heterogeneity is too large to derive meaningful pooled estimates.2 With regard to Fig. 3B, the study by Kim et al.4 was conducted among patients who received a liver transplant and thus cannot be used to estimate prevalence in the general population. The study by Hong et al.5 had a 16.3% prevalence of NAFLD according to supplementary table A,1 which is correct; but in fig. 3b the prevalence was incorrectly calculated at 24.77%. Finally, we identified at least 10 more studies from Asia (Japan and China in particular) that were not included in the meta‐analysis by Younossi et al.1 We have not checked other results presented; however, based on the above errors, we have concerns about the validity and meaningfulness of the study as a whole.