tbuckley/cabot-search huggingface dataset:
Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation
Authors: Brantley D. Coleman, Arthur Marivin, Kshitij Parag-Sharma, Vincent DiGiacomo, Seongseop Kim, Judy S. Pepper, Jason Casler, Lien T. Nguyen, Michael R. Koelle, Mikel Garcia-Marcos
Journal: Molecular Biology and Evolution (2015)

Trimeric G protein signaling is a fundamental mechanism of cellular communication in eukaryotes. The core of this mechanism consists of activation of G proteins by the guanine-nucleotide exchange factor (GEF) activity of G protein coupled receptors. However, the duration and amplitude of G protein-mediated signaling are controlled by a complex network of accessory proteins that appeared and diversified during evolution. Among them, nonreceptor proteins with GEF activity are the least characterized. We recently found that proteins of the ccdc88 family possess a Gα-binding and activating (GBA) motif that confers GEF activity and regulates mammalian cell behavior. A sequence similarity-based search revealed that ccdc88 genes are highly conserved across metazoa but the GBA motif is absent in most invertebrates. This prompted us to investigate whether the GBA motif is present in other nonreceptor proteins in invertebrates. An unbiased bioinformatics search in Caenorhabditis elegans identified GBAS-1 (GBA and SPK domain containing-1) as a GBA motif-containing protein with homologs only in closely related worm species. We demonstrate that GBAS-1 has GEF activity for the nematode G protein GOA-1 and that the two proteins are coexpressed in many cells of living worms. Furthermore, we show that GBAS-1 can activate mammalian Gα-subunits and provide structural insights into the evolutionarily conserved determinants of the GBA–G protein interface. These results demonstrate that the GBA motif is a functional GEF module conserved among highly divergent proteins across evolution, indicating that the GBA-Gα binding mode is strongly constrained under selective pressure to mediate receptor-independent G protein activation in metazoans.
The TGF-β/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia
Authors: R H Rouce, H Shaim, T Sekine, G Weber, B Ballard, S Ku, C Barese, V Murali, M-F Wu, H Liu, E J Shpall, C M Bollard, K R Rabin, K Rezvani
Journal: Leukemia (2015)
Ice Cube Tray–Shaped Insulin Lipoatrophy Throughout the Abdomen in a Subject With Type 2 Diabetes
Authors: Kenji Kohara, Hideaki Kaneto, Shinji Kamei, Masashi Shimoda, Sumiko Hamamoto, Kazuhito Tawaramoto, Michihiro Matsuki, Tomoatsu Mune, Kohei Kaku
Journal: Diabetes Care (2015)

A 71-year-old woman with type 2 diabetes was referred to our hospital because of severe lipoatrophy throughout the whole abdomen induced by insulin therapy. The patient was diagnosed with type 2 diabetes when she was 63 years old and was treated with diet therapy only. When she was 69, her glycemic control became poor and insulin therapy was introduced (before breakfast, 20 units biphasic insulin Novolin 30R). Just after treatment began, she noticed that her abdomen gradually became atrophic, but she left it as it was. HbA1c levels were ∼8–9% (64–75 mmol/mol). She was treated only with biphasic insulin, and other antidiabetes agents were not used. Since her understanding about diabetes was poor, it was possible that she forgot to rotate the insulin injection site. When she was 71 years old, her glycemic control became …
Toward Personalized Guidelines in Bladder Cancer
Authors: Peter E. Clark
Journal: Journal of the National Comprehensive Cancer Network (2015)

s and serves as a reviewer for a variety of medical journals, including the Journal of Urology, Cancer Therapy, and The Lancet. Dr. Clark also is a member of a number of professional societies, including the Southeastern Section American Urological Association, Inc., the Eastern Cooperative Oncology Group, the Society of Urologic Oncology, and the Society for Basic Urologic Research. He is a founding member of the Young Urologic Oncologists, a subset of the Society of Urologic Oncology. Dr. Clark currently serves as Chair of the NCCN Clinical Guidelines Panel for Bladder Cancer and is an Editorial Board member of JNCCN. Toward Personalized Guidelines in Bladder Cancer
Editorial
Authors: K T Weber
Journal: Cardiovascular Research (1998)

On this cold wintry day in December, 1921, George door interrupted his concentration and engaged his startle Conrad was browsing the shelves of his favorite book response.''Enter!'' he exclaimed.store.There, nestled on the shelf between textbooks of As if walking on eggs, 28-year-old Dr. Bernhard Nocht surgery, he found a treasure bound in rich burgundy with made his way into the cabin.Nocht, a naval physician, 1-centimeter-tall gold lettering, written by Edward B.would care for the ships's crew while satisfying his Vedder, M.D., Captain in the U.S. Army Medical Corps, wanderlust to visit distant shores.He reported that rations and published in 1913.This accounting of an illness was on board, including citrus fruit from Spain, baked bread, already acclaimed a masterpiece.Vedder had been awarded fresh vegetables, and fresh as well as canned meats, had the Cartwright Prize of the Alumni of the College of passed his personal inspection.Further
PTH-177 Radiofrequency ablation for complicated barrett’s oesophagus: experience of a tertiary centre in northern ireland at 5 years
Authors: P Hall, O Reed, I Mainie
Journal: Gut (2015)

<h3>Introduction</h3> The 2013 British Society of Gastroenterology (BSG) guideline supports first line use of endoscopic therapy in patients with dysplastic Barrett’s oesophagus or intramucosal carcinoma (IMC).<sup>1</sup>Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) can be used instead of oesophagectomy in fit patients and allows treatment of those unfit for surgery. We aimed to evaluate the outcomes of our centre’s RFA programme after 5 years, in a tertiary referral centre for Northern Ireland. <h3>Method</h3> A patient database was compiled by searching a hospital’s endoscopy reporting system for ‘radiofrequency’, ‘RFA’, and ‘HALO’. We retrospectively gathered histology and follow up data using patient letters and laboratory records. <h3>Results</h3> 45 patients (39M:6F) mean age 67, received RFA for low/high grade dysplasia (LGD, HGD) or IMC. Prior histology demonstrated 3 LGD, 29 HGD and 13 IMC. Average Prague score: C4.4 M5.6. Of these patients who received RFA, 82% (37/45) had required endoscopic mucosal resection (EMR) of visible lesions prior to therapy. A mean of 1.82 sessions of EMR were needed (range 0–7). 77 sessions of RFA were received by the 45 patients (mean 1.71 sessions). 36 patients were treated by the end of 2013 with only 7 of these (19.4%) referred for surgery by the end of 2014. The remaining 80.6% showed either complete eradication of Barrett’s (58%), eradication of dysplasia (17%) or are awaiting further endoscopic therapy with view to eradication of dysplasia (6%). There were no deaths related to endoscopic treatment and no major complications. 2 patients needed stricture dilatation and several had minor bleeding. Those referred for oesophagectomy from the programme fell from 4 in 2011 to only 1 over the last 2 years. This could represent increased confidence in EMR/RFA from the multidisciplinary team (MDT) with time. Of the initial 7 patients referred by the MDT for oesophagectomy only 1 specimen showed carcinoma with submucosal involvement. The remaining specimens showed 2 with IMC (29%), 1 with HGD (14%) and 3 (43%) with Barrett’s metaplasia alone. <h3>Conclusion</h3> Endoscopic therapy is safe and effective in treating complicated Barrett’s. Most patients (82%) will require EMR prior to RFA and this should be incorporated into planned treatment schedules. Our figures show an overall surgery rate of 19% which is falling with time as multidisciplinary confidence with endoscopic therapy improves. We anticipate service expansion, particularly with recent evidence showing benefits in the ablation of LGD.<sup>2</sup> <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Fitzgerald RC, <i>et al</i>. Guidelines on the diagnosis and management of Barrett’s oesophagus. <i>BSG</i>2013 Phoa KN, <i>et al</i>. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia. JAMA 2014;311(12):1209–1217
Bevacizumab in Advanced Angiosarcoma: What Is the Reality?
Authors: Bivas Biswas, Deepak Dabkara
Journal: Journal of Clinical Oncology (2015)

previous preclinical and clinical evidence regarding the use of antiangiogenic therapy in angiosarcoma. Before incorporating these results into clinical practice, it would be prudent to review a few facts. First, although the incidence of angiosarcoma is relatively rare, the sample size of the study was small and, thus, undermines the statistical ability to draw any strong clinical conclusion. Second, a concomitantbiomarker study(eg, plasma level of VEGF, sVEGFR-2, etc) could provide some insight into the antiangiogenic activity in angiosarcoma (preintervention and postintervention change in serum levels of the aforementioned biomarkers), similar to the recent study of sorafenib in pediatric solid tumors. 5 Third, a recent study showed overexpression of the phosphatidylinositol 3-kinase/ Akt/mammalian target of rapamycin pathway in angiosarcoma, 6
Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.
Authors: K W Gilchrist, R Gray, B Fowble, D C Tormey, S G Taylor
Journal: Journal of Clinical Oncology (1993)

PURPOSE The Eastern Cooperative Oncology Group (ECOG) entered 766 patients onto two prospectively randomized surgical adjuvant clinical trials for lymph node-positive breast cancer (T1-3N1M0). Ninety-five percent (n = 728) of eligible patients have complete information on the prognostic covariables under study (tumor necrosis [TN], tumor size, number of positive lymph nodes, age) and a median follow-up duration of 10.3 years. METHODS TN was defined as confluent cell death in invasive areas of primary cancers, visible at 4 x objective lens magnification. Cox proportional hazards models were used to estimate presence versus absence of TN effects on clinical outcomes over full cross-stratification of variables, including delivery of chemotherapy versus observation only. Time-varying effects were modeled using spline functions of time, and by fixing proportional hazards models separately in the time periods 0 to 2 and 2+ years. RESULTS Presence of TN was an independent predictor for time to recurrence (TTR) (P = .007) and for survival (P = .0003) in the overall 10-year follow-up period. Presence of TN was also an independent predictor for TTR and for survival (each P &lt; .0001) in the period 0 to 2 years after diagnosis. Spline function time-modeling calculations showed different hazard ratios in the TN-present (TN+) versus TN-absent (TN-) groups for both TTR and survival (each P &lt; .0001). This difference is changing over time (P = .0001 for TTR, P = .0005 for survival). Once a patient has been disease-free beyond 2 years after diagnosis, presence or absence of TN is irrelevant to future prognosis. CONCLUSION Confluent TN of any dimension in invasive areas of lymph node-positive breast cancer is an independent predictor for early recurrence and death from the disease.
Arabinosyl Cytosine: A Useful Agent in the Treatment of Acute Leukemia in Adults
Authors: ROSE RUTH ELLISON, JAMES F. HOLLAND, MARISE WEIL, CLAUDE JACQUILLAT, MICHEL BOIRON, JEAN BERNARD, ARTHUR SAWITSKY, FRED ROSNER, BERNARD GUSSOFF, RICHARD T. SILVER, ARTHUR KARANAS, JANET CUTTNER, CHARLES L. SPURR, DONALD M. HAYES, JOHANNES BLOM, LOUIS A. LEONE, FARID HAURANI, ROBERT KYLE, J. L. HUTCHINSON, R. JACKSON FORCIER, JOHN H. MOON
Journal: Blood (1968)
Low-Volume Nodal Metastases Detected at Retroperitoneal Lymphadenectomy for Testicular Cancer: Pattern and Prognostic Factors for Relapse
Authors: Farhang Rabbani, Joel Sheinfeld, Hesam Farivar-Mohseni, Antonio Leon, Michael J. Rentzepis, Victor E. Reuter, Harry W. Herr, John A. McCaffrey, Robert J. Motzer, Dean F. Bajorin, George J. Bosl
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the incidence, pattern, and predictive factors for relapse in patients with low-volume nodal metastases (stage pN1) at retroperitoneal lymphadenectomy (RPLND) and identify who may benefit from chemotherapy in the adjuvant or primary setting. PATIENTS AND METHODS: Fifty-four patients with testicular nonseminomatous germ cell tumor had low-volume retroperitoneal metastases (pathologic stage pN1, 1997 tumor-node-metastasis classification) resected at RPLND, 50 of whom were managed expectantly without adjuvant chemotherapy. The dissection was bilateral in 12 and was a modified template in 38 patients. Retroperitoneal metastases were limited to microscopic nodal involvement in 14 patients. Follow-up ranged from 1 to 106 months (median, 31.4 months). RESULTS: Eleven patients (22%) suffered a relapse at a median follow-up of 1.8 months (range, 0.6 to 28 months). The most frequent form of recurrence was marker elevation in nine (18%) patients. Persistent marker elevation after orchiectomy and before retroperitoneal lymphadenectomy was a significant independent predictor of relapse (relative risk, 8.0; 95% confidence interval, 2.3 to 27.8; P = .001). Four of five (80%) patients with elevated markers (alpha-fetoprotein alone in three, alpha-fetoprotein and beta human chorionic gonadotropin in one) suffered a relapse, compared with seven of 45 (15.6%) patients with normal markers. CONCLUSION: Clinical stage I and IIA patients with normal markers who have low-volume nodal metastases have a low incidence of relapse and can be managed by observation only if compliance can be assured. In contrast, patients with elevated markers before retroperitoneal lymphadenectomy have a high rate of relapse and should be considered for primary chemotherapy.
Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen.
Authors: M Roselli, F Guadagni, O Buonomo, A Belardi, V Vittorini, R Mariani-Costantini, J W Greiner, C U Casciani, J Schlom
Journal: Journal of Clinical Oncology (1996)

PURPOSE The ability of interferons (IFNs) to enhance tumor-associated antigen expression may be an important approach to enhance the efficacy of some monoclonal antibody (MAb)-based protocols for tumor diagnosis and/or therapy. The present study was designed to determine whether systemic IFN alpha-2a administration (via the intramuscular [IM] route) could upregulate the expression of tumor-associated glycoprotein-72 (TAG-72) and/or carcinoembryonic antigen (CEA) at histologically confirmed sites of carcinoma. PATIENTS AND METHODS Eighteen patients diagnosed with gastrointestinal (GI) carcinoma received systemic IFN alpha-2a according to four dose schedules. In cohorts I and II, patients received two injections of 3 or 6 x 10(6) U IFN alpha-2a per injection, respectively. Patients in cohorts III and IV received the same doses of IFN alpha-2a, 3 and 6 x 10(6) U, respectively, but three injections were given. Tumor and normal colonic mucosa biopsies were obtained from each patient by endoscopy before IFN alpha-2a and after IFN alpha-2a at surgery. The levels of TAG-72 and CEA expression were measured by (1) immunohistochemistry and reported as percent antigen-positive tumor cells, as well as the relative staining intensity, and (2) a quantitative radioimmunoassay. RESULTS TAG-72 and CEA levels were consistently increased in tumor biopsies taken from patients in cohorts III and IV. For example, of 10 patients treated in cohorts III and IV, eight had enhanced TAG-72 expression when measured either as percentage TAG-72-positive tumor cells or as an increased MAb staining intensity following IFN alpha-2a. CEA expression in tumor biopsies from seven of 10 patients in cohorts III and IV was also elevated following IFN alpha-2a treatment. Quantitative analysis of TAG-72 and CEA levels in tumor biopsies confirmed higher tumor antigen levels following IFN alpha-2a administration. No such increases in TAG-72 or CEA levels were observed in tumor samples taken from patients in cohorts I and II. CEA or TAG-72 expression in samples of histologically confirmed normal colonic mucosa showed little or no change after IFN alpha-2a treatment. CONCLUSION Systemic IFN alpha-2a administration can upregulate TAG-72 and CEA expression at distal tumor sites, which may play an important role in immunodiagnosis and therapy.
MDSCs enhance tumor cell proliferation in a caspase-1 related inflammasome cytokines dependent way
Authors: Qi Zeng, Jesse Qualliotine, Richard Blosser, Drew Pardoll, Young Kim
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Myeloid-derived-suppression cells (MDSCs) are believed to be an important immune evasion mechanism by suppressing T cells. We investigated whether MDSCs have direct T cell independent pro-carcinogenic effect on tumor cells. We sorted the monocytic CD14+/CD11b+/HLA-DRlow MDSCs from
Blood pressure and insulin resistance: role for microvascular function? [Cardiovasc Res 2002;53:271–276]
Authors: E Serné
Journal: Cardiovascular Research (2002)

In a recent issue of Cardiovascular Research , Irving et al. [1] reported on the relationships among microvascular function, blood pressure, and insulin resistance in healthy men. The main objective was to test the hypothesis that defects in microvascular function could explain the relationship between elevated blood pressure and insulin resistance. They report that higher systolic blood pressure was associated with insulin resistance, lower dermal capillary density at rest and during venous occlusion, and impaired maximum dermal blood flow after heating, but not with dilator responses to acetylcholine. Insulin resistance, as assessed by HOMA, did not correlate with indices of microvascular function or structure. It is concluded that the association between hypertension and insulin resistance is unlikely to be explained by altered microvascular function and structure. In contrast, we have demonstrated that higher systolic blood pressure was associated with insulin resistance, capillary recruitment during post-occlusive reactive hyperaemia (PRH), and dilator responses to acetylcholine in both normotensive [2] and hypertensive subjects …
Assessment of changes in the burden of Chlamydia trachomatis infection in the context of widespread opportunistic chlamydia screening: Pgp3 seroprevalence measured in a series of nationally representative cross-sectional household surveys
Authors: Sarah C Woodhall, Gillian Wills, Paddy Horner, Rachel Craig, Jennifer S Mindell, Gary Murphy, Myra McClure, Kate Soldan, Anthony Nardone, Anne M Johnson
Journal: The Lancet (2015)
Time to End the Mixed—and Often Incorrect—Messages About Prevention and Treatment of Atherosclerotic Cardiovascular Disease⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Philip Greenland, Donald Lloyd-Jones
Journal: Journal of the American College of Cardiology (2007)
Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).
Authors: Kimmie Ng, Alan P. Venook, Kaori Sato, Bruce W. Hollis, Donna Niedzwiecki, Cynthia Ye, I-Wen Chang, Bert H. O'Neil, Federico Innocenti, Heinz-Josef Lenz, Charles David Blanke, Robert J. Mayer, Charles S. Fuchs, Jeffrey A. Meyerhardt
Journal: Journal of Clinical Oncology (2015)

507 Background: Prospective epidemiologic data suggest that higher levels of 25-hydroxyvitamin D [25(OH)D] are associated with improved survival in patients with colorectal cancer (CRC), however, the relationship between 25(OH)D and outcome in metastatic CRC, specifically, is unknown. Methods: We prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated metastatic CRC patients enrolled in CALGB 80405, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS WT amendment. Progression-free survival (PFS) was a secondary endpoint. Plasma 25(OH)D levels were measured at baseline by radioimmunoassay, and dietary and lifestyle behaviors collected from self-administered questionnaires. Cox proportional hazards models were used to calculate hazard ratios adjusted for other prognostic factors. In sensitivity analyses, patients who died within 3 or 6 months of blood draw were excluded to address the possibility of reverse causation. Results: Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL (range 2.2-72.7). Older and black patients, those with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (vs. 0), higher body-mass index, lower physical activity, and blood draws during the winter and spring had significantly lower levels of 25(OH)D. Patients in the highest quintile of 25(OH)D had significantly improved OS compared to those in the lowest after adjusting for pathologic and clinical prognostic factors (median 32.6 vs. 24.5 months; HR 0.67, 95% CI, 0.53-0.86; p trend 0.002). Increasing concentrations of 25(OH)D were also associated with improved PFS (median 12.2 vs. 10.1 months; HR 0.80, 95% CI, 0.64-1.01; p trend = 0.02). The results were consistent across subgroups of patient characteristics, including KRAS status, and remained unchanged after excluding patients who died within 3 or 6 months of blood draw. Conclusions: Higher concentrations of plasma 25(OH)D are associated with significantly improved survival in metastatic CRC patients treated with chemotherapy + biologics. Randomized trials of vitamin D supplementation are warranted and are currently underway.