tbuckley/cabot-search huggingface dataset:
Acute General Edema of the Brain in Children with Head Injuries
Authors: Wilfred Pickles
Journal: New England Journal of Medicine (1950)

A FEW months ago I presented to the New England Surgical Society some observations1 based on a series of 7 children, varying in age from ten months to eleven years, who had presented symptoms and signs strongly suggestive of extradural hemorrhage, but whose recovery without operation was so rapid and complete as to cast doubt on this diagnosis. In most cases the child fell and struck his head on the floor or ground, and in about half, there was initial unconsciousness with fairly prompt recovery from this state. Only 2 of the children suffered from traumatic shock. At an interval . . .
Meta-analysis confirms raised risk of bladder cancer from pioglitazone
Authors: B. Kermode-Scott
Journal: BMJ (2012)

A new meta-analysis1 seems to confirm findings from a nested, case-control study published in the BMJ in May2 that thiazolidinediones are associated with an increased risk of bladder cancer in people with type 2 diabetes.

Both analyses also found that in the studies that looked at individual drugs in this class pioglitazone, but not rosiglitazone, was associated with an increased risk of bladder cancer.

In the BMJ study, Azoulay and colleagues from McGill University in Montreal looked at a cohort that included 115 727 new users of oral hypoglycaemic agents, of whom 470 were given a diagnosis of bladder cancer during follow-up …
LOSS OF SPARC IN P53-NULL ASTROCYTES PROMOTES MACROPHAGE ACTIVATION AND PHAGOCYTOSIS RESULTING IN DECREASED TUMOR SIZE AND TUMOR CELL SURVIVAL
Authors: S. A. Rempel, S. L. Thomas, C. R. Schultz, E. Mouzon, W. A. Golembieski, R. El Naila, A. Radakrishnan, K. R. Bobbitt, N. Lemke, J. A. Gutierrez, L. M. Poisson
Journal: Neuro-Oncology (2014)

BACKGROUND: Both enhanced SPARC expression and the loss of p53 tumor suppressor gene are changes that occur early in glioma development. Both SPARC and p53 regulate glioma cell survival by inverse effects on apoptotic signaling. Therefore, during glioma formation, the upregulation of SPARC may cooperate with the loss of p53 to enhance cell survival and inhibit apoptosis. This study determined whether the loss of Sparc in astrocytes that are null for p53 would result in reduced cell survival and tumor formation and increased tumor immunogenicity in an in vivo xenograft brain tumor model. METHODS: p53-null and Sparc-null mice were bred to obtain heterozygotes. These were crossed to obtain p53-null/Sparc-null neonates, which served as the source of p53-null/Sparc-null astrocytes for comparison to genetically-matched, control p53-null/Sparc-WT astrocytes. In vitro, Sparc loss was assessed using colony formation in soft agar, proliferation assay, flow cytometry, and Annexin V analysis. Orthotopic xenograft implantation was used to assess Sparc loss on tumor growth, proliferation, collagen deposition, and macrophage/microglia recruitment. RESULTS: In vitro, Sparc loss in p53-null astrocytes resulted in increased cell proliferation (2.7-fold; p < 0.01), but decreased cell survival (WT = 7.2% vs. null = 18.56% apoptotic cells) and a longer cell cycle recovery (2 days) after serum-withdrawal. Furthermore, Sparc loss suppressed growth in soft agar. Histomorphological analysis of CD68 and PAS ± diastase staining of tumor sections demonstrated that Sparc loss promoted macrophage/microglial activation (day 7 = 1.35-fold and day 50 = 1.93-fold; p < 0.001) and phagocytic morphology, respectively. At 7 days, Sparc-null tumors had decreased tumor cell survival, proliferation (MIB-1 for WT = 7.1% vs. null = 0.1%; p = 0.0345), and reduced tumor size (WT = 0.839 mm2 vs. null = 0.199 mm2; p = 0.0091). In addition, Sparc loss altered collagen deposition (WT = collagen bundles vs. null = long fiber structure). CONCLUSIONS: Our results indicate that Sparc loss significantly reduced the ability of p53-null astrocytes to recover from stress in vitro, and to survive and proliferate in vivo. This inability to grow in vivo was associated with an increase in macrophage/microglial activation and phagocytosis. Therefore, we conclude that the loss of p53 in the early stages of glioma formation may cooperate with the induction of SPARC to potentiate cancer cell survival and escape from immune surveillance. We propose that in the background of p53 loss/mutation, therapeutically suppressing SPARC alone, or in combination with other therapies, should promote the ability of patient's immune system to eradicate the tumor. SECONDARY CATEGORY: Immunobiology & Immunotherapy.
Abstract 3192: Lin28 promotes growth of prostate cancer cells and activates the androgen receptor.
Authors: Ramakumar Tummala, Nagalakshmi Nadiminty, Yezi Zhu, Wei Lou, Christopher P. Evans, Allen C. Gao
Journal: Cancer Research (2013)

Abstract Purpose: Lin28 is essential for stem cell viability and pluripotency. Recently Lin28 expression has been linked to several malignancies and its mechanisms of action proposed to be both let-7-dependent and -independent. It is a master regulator of let-7 miRNA biogenesis as well as a regulator of translation of a multitude of eukaryotic proteins. This study tested the hypothesis that Lin28 is overexpressed in prostate cancer (CaP) and that it activates the androgen receptor (AR) and promotes growth of CaP cells. Experimental Design: Human clinical CaP samples were analyzed for the expression of Lin28 by qRT-PCR, Western blotting and immunohistochemistry. Lin28 was transfected into a panel of CaP cell lines and growth was monitored. LNCaP cells stably expressing Lin28 were generated and growth was examined. Clonogenic ability of CaP cells expressing Lin28 was determined by colony formation and soft agar assays. Increase in expression of the AR and subsequent increase in transcription of AR-target genes were analyzed by qRT-PCR, luciferase assays and ELISA. LNCaP cells stably expressing Lin28 were injected into nude mice and tumorigenesis was monitored. Results: Lin28 was found to be overexpressed in clinical CaP compared to the benign tissues. Overexpression of Lin28 enhanced while downregulation of Lin28 reduced growth of CaP cells. Lin28 enhanced the ability of CaP cells to form colonies in anchorage-dependent and -independent manners. LNCaP cells stably expressing Lin28 exhibited significantly higher tumorigenic ability in vivo. Furthermore, Lin28 induces expression of the AR and its target genes such as PSA and NKX3.1. Conclusions: Lin28 promotes growth of CaP cells in vitro and in vivo. Lin28 induces expression and activation of the AR. Our findings suggest an important role of Lin28 in CaP development and activation of the AR axis. Citation Format: Ramakumar Tummala, Nagalakshmi Nadiminty, Yezi Zhu, Wei Lou, Christopher P. Evans, Allen C. Gao. Lin28 promotes growth of prostate cancer cells and activates the androgen receptor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3192. doi:10.1158/1538-7445.AM2013-3192
Abstract LB-516: PDZ-RhoGEF promotes glioblastoma cell invasion, proliferation and survival
Authors: Aneta Kwiatkowska, Zhiwan Dong, Vincent M. Paulino, Nhan L. Tran, Rosamaria Ruggieri, Marc H. Symons
Journal: Cancer Research (2012)

Abstract Invasion of glioblastoma cells into the surrounding brain parenchyma is a critical parameter of this disease as it hampers complete surgical resection of the tumor mass. Glioblastoma tumors are highly proliferative and resistant to radio- and chemo-therapy, thereby leading to tumor recurrence. Rho family members have been shown to control both the invasive and proliferative behavior of tumor cells. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs). In this study we focused on PDZ-RhoGEF, as its role in glioblastoma is not known. It has been shown that invading glioblastoma cells need contractile force to squeeze their nucleus through narrow spaces that are characteristic of the brain parenchyma (Beadle et al, Mol. Biol. Cell (2008) 19: 3357). We found that depletion of PDZ-RhoGEF in U87 and SNB19 glioblastoma cells strongly inhibits cell migration across a small (3 μm) pore size filter, a process which necessitates nuclear squeezing. PDZ-RhoGEF depletion also inhibits cell migration across a larger (8 μm) pore size filter, albeit to a lesser extent than in the squeezing assay. Interestingly, cells lacking PDZ-RhoGEF display multi-lobed lamellae, suggesting a defect in cell polarization. In addition, PDZ-RhoGEF depletion strongly inhibits glioblastoma cell invasion into ex vivo brain slices. In vitro studies have demonstrated that PDZ-RhoGEF can act on both RhoA and RhoC. The roles of these GTPases in the invasive behavior of glioblastoma have not been reported to date. Interestingly, we found that depletion of RhoC strongly inhibits brain slice invasion and nuclear squeezing, whereas depletion of RhoA has no significant effect on these functions. Thus, taken together, these data suggest that PDZ-RhoGEF largely acts by activating RhoC to stimulate glioma cell invasion. Our preliminary data also indicate that PDZ-RhoGEF mediates glioma cell proliferation and survival. In conclusion, our findings suggest that PDZ-RhoGEF is a potential therapeutic target for glioma therapy. 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-516. doi:1538-7445.AM2012-LB-516
Ga-67 Scintigraphy in Multicentric Castleman’s Disease
Authors: SHUNG-SHUNG SUN, FENG-JU CHUANG, CHUN-YI LIN, CHIA-HUNG KAO
Journal: Clinical Nuclear Medicine (2002)

SUN, SHUNG-SHUNG M.D.; CHUANG, FENG-JU M.D.; LIN, CHUN-YI M.D.; KAO, CHIA-HUNG M.D. Author Information
Abstract P2-02-02: Uptake and Predictors of Screening Breast MRI in High Risk Women
Authors: MS Beattie, E Blumenthal, J Creasman, E Cheung, B. Crawford
Journal: Cancer Research (2010)

Abstract BACKGROUND: Screening breast MRI is recommended in: BRCA carriers, their first degree relatives who have yet to test, and women with lifetime breast cancer risks of over 20-25%. It is unclear, however, whether women who receive screening breast MRI meet any of these criteria. As screening breast MRI becomes more available and accepted, it is also important to describe its uptake and identify its predictors. OBJECTIVE: To determine the uptake over time of screening breast MRI, as well as predictors of receiving screening breast MRI, in a cohort of women at high risk of hereditary breast cancer. METHODS: We surveyed all cancer-free women who enrolled in the UCSF Cancer Risk Program to determine their uptake of screening breast MRI, including their frequency of screening and the results of this screening. We also queried these women regarding their their risk perception, cancer worry, knowledge of high-risk screening recommendations, and their satisfaction with clinical care. We linked survey data to clinical and demographic data. Descriptive and comparative statistics, as well as multivariate logistic regression, were used to analyze this data. RESULTS: The survey response rate was 80% (n = 433) and the median follow up time was 2.7 years (range 0.5 — 12 years). The uptake of screening breast MRI doubled between 2005 and 2006, and doubled again between 2006 and 2008, with an overall uptake of 25% for ever receiving a screening breast MRI. Of the 92 BRCA carriers in this cohort, 74% reported every receiving a screening breast MRI compared to 18% of non-BRCA carriers (P&amp;lt;0.01). The mean age of first screening breast MRI in this cohort was 40 (range 25-61) compared to the mean age overall of 47 (p = 0.03). Ten percent of women who received screening breast MRI reported that their study required a “call-back” and/or further imaging. Using the BRCAPRO risk prediction model to calculate lifetime risk, without knowing BRCA resutls, 28% of this population would meet the 20% lifetime risk threshold. When BRCA results are incorporated into this risk model, 20% of this population would meet the 20% lifetime risk threshold. Variables associated with obtaining a screening breasat MRI are in the table 1 below. Table 1. Variables independently associated with screening breast MRI use in 433 high risk women withou t breast cancer CONCLUSIONS: Screening breast MRI is growing substantially. Its use to date demonstrates adherence with high-risk recommendations and guidelines. BRCA positive status is the strongest predictor of its uptake, and most BRCA carriers report receiving at least one screening breast MRI. Early trends indicate that variables not associated with risk, such as site of care (public versus university hospital) and race, may play a role in the uptake of screening breast MRI as its use becomes more widespread. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-02.
Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study
Authors: John P. DeVincenzo, Matthew W. McClure, Julian A. Symons, Hosnieh Fathi, Christopher Westland, Sushmita Chanda, Rob Lambkin-Williams, Patrick Smith, Qingling Zhang, Leo Beigelman, Lawrence M. Blatt, John Fry
Journal: New England Journal of Medicine (2015)

BACKGROUND Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality. There is no known effective therapy. METHODS We conducted a randomized, double-blind, clinical trial in healthy adults inoculated with RSV. Participants received the oral nucleoside analogue ALS-008176 or placebo 12 hours after confirmation of RSV infection or 6 days after inoculation. Treatment was administered every 12 hours for 5 days. Viral load, disease severity, resistance, and safety were measured throughout the 28-day study period, with measurement beginning before inoculation. The primary end point was the area under the curve (AUC) for viral load, which was assessed immediately before administration of the first dose through the 12th day after inoculation in participants infected with RSV. RESULTS A total of 62 participants received placebo or one of three ALS-008176 dosing regimens: 1 loading dose of 750 mg followed by 9 maintenance doses of 500 mg (group 1), 1 loading dose of 750 mg followed by 9 maintenance doses of 150 mg (group 2), or 10 doses of 375 mg (group 3). In the 35 infected participants (23 of whom were treated with ALS-008176), the AUCs for viral load for groups 1, 2, and 3 and the placebo group were 59.9, 73.7, 133.4, and 500.9 log10 plaque-forming-unit equivalents × hours per milliliter, respectively (P≤0.001). The time to nondetectability on polymerase-chain-reaction assay (P<0.001), the peak viral load (P≤0.001), the AUC for symptom score (P<0.05), and the AUC for mucus weight were lower in all groups receiving ALS-008176 than in the placebo group. Antiviral activity was greatest in the two groups that received a loading dose--viral clearance was accelerated (P≤0.05), and the AUC for viral load decreased by 85 to 88% as compared with the placebo group. Within this small trial, no viral rebound or resistance was identified. There were no serious adverse events, and there was no need for premature discontinuation of the study drug. CONCLUSIONS In this RSV challenge study, more rapid RSV clearance and a greater reduction of viral load, with accompanying improvements in the severity of clinical disease, were observed in the groups treated with ALS-008176 than in the placebo group. (Funded by Alios BioPharma; ClinicalTrials.gov number, NCT02094365.).
Abstract 84: Evidence supporting a role of FKBP51 in melanoma pathogenesis
Authors: Sanjeev K. Srivastava, Sumit Arora, Arun Bhardwaj, Jonathan G. Scammell, Laurie B. Owen, William E. Grizzle, Ajay P. Singh, Seema Singh
Journal: Cancer Research (2012)

Abstract Melanoma accounts for the majority of skin tumor-related deaths worldwide. The tumors originate from melanocytes and are associated with risk factors such as ultraviolet radiation exposure, fair skin type, and predisposing gene mutations. Although there has been some progress in early melanoma diagnosis, current therapeutic modalities still fail frequently in treating this deadly malignancy once it has metastasized. FKBP51 is a high molecular weight FK506-binding protein involved in the regulation of diverse biological processes. Importantly, it has been shown to be overexpressed in melanoma, activate anti-apoptotic NF-kB signaling, and inhibit apoptosis in irradiated melanoma cells. In this study, we investigated the role of FKBP51 in melanoma pathogenesis in a set of in vitro experiments. FKBP51 was stably repressed in two metastatic melanoma cell lines, A375-SM and FEMX-1, through short-hairpin RNA (shRNA)-mediated silencing and its effect on melanoma phenotype was examined. Silencing of FKBP51 led to a decrease in growth, clonogenicity, motility and invasiveness of both the melanoma cell lines, whereas enhanced cell-cell interaction was observed. Immunoblot analysis demonstrated loss of mesenchymal markers N-cadherin, vimentin, Slug and Snail and gain of epithelial marker, E-cadherin in FKBP51-silenced A375-SM and FEMX-1 cells, indicating a role of FKBP51 in epithelial to mesenchymal transition (EMT) of melanoma cells. Interestingly, in FKBP51-silenced melanoma cells, we also observed a decreased production of interleukin-8 (IL-8/CXCL-8), a chemokine that has earlier been shown to promote melanoma growth, metastasis and angiogenesis. Altogether, these studies provide experimental evidence for a functional role of FKBP51 in altered growth and malignant behavior of the melanoma cells. 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 84. doi:1538-7445.AM2012-84
TCT-838 Management of Drug Eluting Stent In-Stent Restenosis: A Systematic Review and Meta-Analysis
Authors: Sachin S. Goel, Rama Dilip Gajulapalli, Ganesh Athappan, Supriya Gupta, Stephen Ellis, E. Murat Tuzcu, Samir Kapadia
Journal: Journal of the American College of Cardiology (2013)
Abstract C35: Rapid assessment of aneuploidy using 5 minute oligo-FISH probes
Authors: Patricia McGrath, Sean Bradley, Joan Aurich-Costa, Carrie Ng, Susan Selvaggio
Journal: Cancer Research (2009)

Abstract More than 15 years ago, development of non-radioactive FISH probes revolutionized clinical cytogenetics and FISH is now routinely used for mapping genes, detecting pathogenic DNA, and diagnosing cancers and genetic diseases. However, most FISH applications rely on probes generated from large genomic fragments (BAC, YAC or plasmids), cDNA, or PCR generated fragments. The large probe size (200–600bp) results in poor cell penetration necessitating long, 8 to 16 hours hybridization. Furthermore, large BAC probes require high probe concentration and stringent wash conditions. We recently developed short (30mer), synthetic Oligo-FISH probes targeting highly repetitive sequences which offer several advantages for assessing aneuploidy, including performance in &amp;lt; 10 min compared to 8–16 hours required for BAC probes. In addition, since Oligo-FISH probes hybridize at low stringency, it is possible to perform at least 6 successive 4 probe hybridizations without damaging cellular DNA, making it possible to determine aneuploidy in all 24 chromosomes on the same slide in &amp;lt; 24 hours. Here we show results using Oligo-FISH probes specific for chromosomes: 7, 3, 9q12, and 17 designed to detect aneuploidy in urothelial cells. After optimizing probe design, we identified sequences available in the human genome database that contain chromosome specific alpha—satellite or satellite sequences. Next, we prepared urothelial slides and optimized denaturation and hybridization times. After establishing optimum Oligo-FISH conditions, we tested urine samples from 5 healthy volunteers. Our results, obtained in &amp;lt; 3 hours show Analytical Sensitivity &amp;gt; 98% and S/N&amp;gt; 2. Urothelial carcinomas account for more than 90% of all bladder cancers and more than 54% of these newly diagnosed carcinomas are superficial, non-invasive transitional cell carcinomas, which has the highest rate of recurrence and requires life-long diagnostic surveillance. The current standard methods for bladder cancer include cystoscopy and cytology which are invasive, expensive and insensitive. Citation Information: Cancer Res 2009;69(23 Suppl):C35.
TRANSITION TO STAGE D HEART FAILURE AMONG STABLE OUTPATIENTS WITH SYSTOLIC HEART FAILURE
Authors: Andrew McCue, Jeffrey Hedley, Ayman S. Tahhan, Jonathan B. Bjork, Nisarg Patel, Alanna Morris, Robert Cole, Divya Gupta, J. David Vega, Andrew Smith, Vasiliki Georgiopoulou, Andreas Kalogeropoulos
Journal: Journal of the American College of Cardiology (2016)
AB1014 The Value of an Automated Ultrasound System in the Detection of Synovitis
Authors: R. Mueller, M. Gruenke, J. Wendler, F. Schuch, H.-P. Karina, I. Boettger, R. Jakobs, H. Schulze-Koops, J. von Kempis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The detection of joint swelling caused by synovitis is important for the diagnosis and assessment of inflammatory arthritis. Ultrasound (US) and MRI have proven to be more sensitive and reliable than physical examination, but a comprehensive examination of affected joints with these techniques is time consuming and expensive. The automated breast volume scanner (ABVS) was developed to acquire serial B-mode pictures of the female breast and these data can be analysed in all three dimensions. <h3>Objectives</h3> To analyse the value of automated grey scale B mode US employing the ABVS system in detecting synovitis of the finger joints compared to manual ultrasound and physical examination, using MRI as gold standard. <h3>Methods</h3> 19 consecutive patients suffering from rheumatoid (n=15) or psoriatic (n=4) arthritis with at least one swollen finger joint were included. Automated and manual US were conducted using the ACUSON S2000™. The ABVS transducer was equipped with a linear array used with a frequency of 11 MHz. Each automatic sweep of the scanner generated 15.4 x 16.8 x 2.5 cm volume data sets. The system was set to perform an automatic scanning time of 65 s per scan with a slice thickness of 0.5 mm. The dorsal and palmar side of each hand were scanned separately. Multiplanar reconstruction enabled examination of the images at multiple levels for the presence of synovitis. <h3>Results</h3> Automated US detected 12.0, manual ultrasound 14.2, MRI 13.4, and clinical examination 4.1 swollen joints on average, respectively, per patient. The inter-observer reliability of both assessors for automated and manual US, MRI, and physical examination, was 66.9%, 72.7%, 95.1%, and 88.9%, respectively. A double assessor detection of joint swelling with MRI was used as gold standard. For the other methods, single observer detection was chosen. 84.3% of the joints classified as positive on MRI were confirmed by automated ultrasound, 85.5% on manual US, and 36.0 on physical examination. This translated into a sensitivity of 83.5%, 85.5%, and 36.0% for the three methods, respectively. <h3>Conclusions</h3> Automated US is a simple and time sparing option for the effective detection of synovitis in patients with inflammatory arthritis. <h3>Disclosure of Interest</h3> R. Mueller: None declared, M. Gruenke: None declared, J. Wendler: None declared, F. Schuch: None declared, H.-P. Karina: None declared, I. Boettger: None declared, R. Jakobs Employee of: Siemens, H. Schulze-Koops: None declared, J. von Kempis: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2059