tbuckley/cabot-search huggingface dataset:
HG-14 * CLINICAL, RADIOGRAPHIC, AND HISTOLOGIC CHARACTERISTICS OF LONG-TERM SURVIVORS OF DIFFUSE INTRINSIC PONTINE GLIOMA: A REPORT FROM THE INTERNATIONAL DIPG REGISTRY
Authors: L. M. Hoffman, U. Bartels, L. Miles, C. Hawkins, S. Goldman, S. Leary, T. Hassal, J. Minturn, R. Packer, N. Foreman, K. Warren, A. Broniscer, E. Broxon, C.-S. Shih, J. Leach, B. Jones, J. Baugh, B. Hacker, B. Lerme, C. Jones, S. Savage, J. Kirkendall, R. Doughman, M. Wollman, L. Millett, R. O'Keefe, E. Bouffet, D. G. van Vuurden, M. Fouladi
Journal: Neuro-Oncology (2015)

Children with diffuse intrinsic brainstem glioma (DIPG) have a median survival of less than 1 year despite radiation ± chemotherapy. The International DIPG Registry, a collaborative effort among researchers in North America and Australia has enrolled 395 patients with data for over 900 patients committed from 35 institutions. Among the 395 patients, 32 long-term survivors (LTS) (overall survival [OS] ≥2 years) have been identified. Preliminarily, we report clinical, radiographic, and histologic data for 75 of 395 patients, including the 32 LTS and 43 in the comparison (C) group. On central radiographic review, 5 were deemed not to represent DIPG (3 LTS and 2 C). Median age at diagnosis for LTS and C groups was 5.5 and 6.1 years, respectively. Fifty-seven percent of LTS had >6 weeks between onset of symptoms and diagnosis versus 28% for the comparison group (p < 0.05). Incidence of signs and symptoms at diagnosis (cranial nerve, cerebellar, or pyramidal) was similar in both groups. All patients, except 3 LTS, underwent radiation at diagnosis; all but 6 received adjunct chemotherapy. Median OS was 28.4 and 10.8 months for the LTS and C groups, respectively. Two patients (1 LTS) had an H3.3K27M mutation and 2 (1 LTS) had an H3.1K27M mutation. Biology data from 25 other patients from autopsy (n = 12) or biopsy (n = 13) are under analysis. Presence of enhancement on diagnostic imaging was associated with poorer survival (p = 0.02). There was no significant difference in radiographic evidence of hemorrhage, necrosis, diffusion restriction, or tumor size between LTS and C groups. Preliminary data in children with DIPG suggest that LTS have a longer duration of presenting signs and symptoms and less often display radiographic evidence of enhancement at diagnosis. Complete clinical, radiographic, and biology (where available) data on all 395 patients enrolled are currently being analyzed and will be presented.
Abstract 1510: Blockade of the mTOR/NF-κB signaling axis augments prostate cancer treatment responses through suppression of a microenvironment-derived DNA damage secretory program
Authors: Yu Sun, Ilsa Coleman, Peter Nelson
Journal: Cancer Research (2012)

Abstract Background/Rationale: Resistance to cytotoxic chemo- and radiotherapy is a common event in advanced prostate cancers. While resistance is established as a consequence of cancer cell intrinsic genetic and epigenetic changes, emerging evidence indicates that therapy failure is also caused by cell extrinsic factors such as cytokines, growth factors, proteases and other soluble ligands generated from damaged stromal cells in the tumor microenvironment (TMEN). We recently reported a unique feature of stromal cells, namely a DNA damage secretory phenotype (DDSP) resulting from genotoxic therapeutics. Thus, anti-cancer therapies that cause DNA damage responses (DDR), unexpectedly, trigger pro-survival signaling in neoplastic or pre-neoplastic cells and may promote subsequent therapy resistance. Results: In this study, we show that molecular inhibition of the mammalian target of rapamycin (mTOR) through genetic or chemical approaches suppresses a cellular secretory program resulting from exposure to genotoxic agents. We identified a physical association between mTOR and the I-kappa-B kinase (IKK) complex which is activated by DNA damage stimuli, and found IKKα to be the major subunit that directly interacts with mTOR while assembling the IKK complex. Rapamycin abrogates IKKα phosphorylation, IαBβ degradation and the central action-p65/p50 nuclear translocation. Thus, IKK catalytic subunits are not equally implicated in propagating damage signals to NF-κB, with IKKα playing the pivotal role. We determined that the mTOR/Raptor complex is activated by genotoxic stress and promotes NF-κB signaling. Suppressing mTOR dramatically abolished transcriptional levels of NF-κB target genes. We also determined that paracrine-acting DDSP factors are regulated through both transcriptional and post-transcriptional mechanisms, as upregulation of S6K and downregulation of 4E-BP1 play essential and synergistical roles in synthesis of DDSP factors. Finally, we determined that mTORC1 is the predominant mediator of the development of the DDSP phenotype, and it receives signals from upstream kinases. Interestingly, PI3K is not required for signal transduction of damage responses in prostate fibroblasts, which occurs through Akt phosphorylation caused by activated p38 MAPK signaling. Conclusions: These studies establish that mTOR is a novel target for therapeutic intervention in the mitigation of resistance mechanisms derived from the tumor microenvironment following genotoxic cancer treatments. These studies suggest that mTOR inhibitors may have efficacy in augmenting tumor responses to ionizing radiation and/or chemotherapy. 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 1510. doi:1538-7445.AM2012-1510
Abstract LB-332: High-throughput proteomic analysis identifies protein S as a potential modulator of androgen-independent prostate cancer
Authors: Punit Saraon, Keith Jarvi, Eleftherios P. Diamandis
Journal: Cancer Research (2011)

Abstract Prostate cancer is the most commonly diagnosed and second leading cause of death due to cancer in men. Androgen deprivation remains the mainstay therapy, which is efficient in shrinking androgen-dependent tumors. However, many men eventually stop responding to this treatment, progressing to a more lethal androgen-independent prostate cancer. The mechanisms mediating these transitions remain unknown, and as a result, there are no effective treatments. We hypothesize the presence of specific modulators, important for the progression to androgen-independency. To test this, we performed high-throughput proteomic analysis on the conditioned media of the androgen-dependent cell lines LNCaP and VCaP, androgen-independent cell lines LNCaP-SF, DU-145, PC3, PPC1, 22Rv1, as well as a normal prostate cell line (RWPE). This allowed us to compile a comprehensive data set, permitting us to mine for differentially secreted proteins that could serve as potential markers for androgen-independent cancers. We utilized quantitative real-time PCR, as well as in vitro wound healing assays to corroborate our proteomic analysis results. We were able to identify the anti-coagulant factor, Protein S (PROS1), as a potential modulator and marker of androgen-independence. Based on spectral counts, PROS1 was found highly secreted in all the androgen-independent cell lines, with no detectable secretion in the normal or androgen-dependent cell lines. The gene expression profile of the androgen-independent cell lines also maintained the over-expression of PROS1, when compared to the normal and androgen-dependent cell lines, while only prostate cancer tissue samples showed an upregulation of PROS1. Furthermore, recombinant PROS1-treated LNCaP cells demonstrated an increase in wound repair and invasive growth potential, implying that PROS1 may have functional roles outside of the coagulation pathway. Our results suggest that PROS1 is involved in the progression of androgen-independent prostate cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-332. doi:10.1158/1538-7445.AM2011-LB-332
Abstract 1352: Shp2 is required for CML initiation and maintenance
Authors: Shengqing Gu, Gordon Chan, Benjamin G. Neel
Journal: Cancer Research (2012)

Abstract Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) caused by the constitutively activated BCR-ABL tyrosine kinase. CML progresses from an initial chronic phase, through an accelerated phase, to a final and fatal blast crisis. Current first-line therapy for CML involves tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinibs. However, TKIs don't completely cure CML, as revealed by low complete molecular response rate and frequent disease relapse upon drug withdrawal. Studies of patient samples and mouse models indicate that this most likely results from lack of dependence of CML stem cells (CML-SCs) on BCR-ABL for survival. It is important to further identify potential targets of CML-SC. Shp2 is a non-receptor protein tyrosine phosphatase involed in RTK, cytokine, and integrine signaling pathways, and is a target of Abl kinase during cell proliferation. It is required for survival and maintenance of normal hematopoietic stem cells (HSCs). In the context of CML, BCR-ABL constitutively phosphorylates Gab2, which then binds to Shp2, resulting in its inappropriate activation of downstream pathways, including the Ras-Erk cascade. Gab2 is required for CML initiation in vivo. We hypothesized that Shp2 is required for CML development from the stem cell level and might be an effective target for treatment of CML. Using our induced Shp2 deletion tools, we found that Shp2 is required for CML initiation and maintenance in a bone marrow transplant model of CML. Moreover, primitive CML cells undergo elevated cell death upon Shp2 knockout. This implicates Shp2 as a potential target for CML therapy in future. 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 1352. doi:1538-7445.AM2012-1352
Abstract 3884: A novel, <i>in vitro</i> tankyrase 1 trans-ribosylation assay
Authors: Jay George, Gabriel Jon Benton, Sandra Woodgate, Hai Xu
Journal: Cancer Research (2012)

Abstract The poly (ADP-ribose) polymerase, tankyrase 1, is an encouraging pharmacological target for cancer therapy. First discovered by its association with the TRF1, tankyrase 1 plays an important role in the maintenance of telomere length, sister telomere association, and mitotic spindle organization. More recently, interactions between tankyrase 1 and axin were shown to stabilize β-catenin and modulate Wnt signaling, enabling selective targeting of the Wnt pathway with tankyrase inhibitors. In addition, tankyrase 1 has also demonstrated potential as a target for synthetic lethality for BRCA-deficient cancers. Given the effect on these cancer-associated pathways, there is a growing interest for identifying tankyrase-specific inhibitors. Historical methods to evaluate tankyrase activity are not amenable for high throughput screening. Limited availability of the full length enzyme required radioactivity to attain the needed sensitivity. Truncation of tankyrase 1 improved solubility and increased availability, but the physiological response may not be equivalent to the full length enzyme. Many of these assays have also used modified substrates where molecules such as fluorescein or biotin are linked to NAD without characterizing the effects on enzyme activity. Most historical assays have also relied on measuring autoribosylation of tankyrase 1; whereas, transribosylation may be more relevant for assessing the activity of tankyrase 1 on other molecules. To address these issues, we have developed a novel, in vitro, high throughput assay for evaluating the transribosylation activity of tankyrase 1. This is accomplished using an ELISA format which semi-quantitatively detects poly (ADP-ribose) (PAR) deposited onto immobilized histone proteins by tankyrase 1. An anti-PAR monoclonal antibody, goat anti-mouse IgG-HRP conjugate, and HRP substrate generate a colorimetric or chemiluminescent signal, and the conversion of substrate correlates with tankyrase 1 activity. This assay ensures physiological significance by utilizing the full length enzyme and unmodified substrate in a transribosylation format, providing sensitivity down to pmols of enzyme. This assay is utilized to demonstrate the specificity of the tankyrase 1 inhibitor, XAV939, for tankyrase 1 compared to PARP1 and to reveal differential effects of activated DNA for full-length tankyrase 1 compared to the truncated enzyme. 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 3884. doi:1538-7445.AM2012-3884
THU0105 Familial Risks of RA in Relation to Type of Affected Relatives, Age, Sex, and RF/ACPA
Authors: T. Frisell, M. Holmqvist, H. Källberg, L. Klareskog, L. Alfredsson, L. Padyukov, J. Askling
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although it is widely accepted that RA aggregates in families, population-based studies are few. The magnitude of the aggregation and whether it differs by disease characteristics also remains unclear. <h3>Objectives</h3> To estimate the familial aggregation of RA in three population-representative samples, and to test if familial aggregation is modified by type of relative, sex, RF/ACPA status, and age at RA onset. <h3>Methods</h3> Register-based case-control study in the Swedish total population. RA was ascertained through the nationwide Patient register (N=88639), the clinical Swedish Rheumatology Quality register (N=11519), and the EIRA case-control study (N=2871). First and second degree relatives were ascertained through the Swedish Multi-Generation Register. Familial risks and 95% confidence intervals (CI) where calculated using conditional logistic regression and expressed as odds ratios (OR). <h3>Results</h3> Consistent across data sources, the familial OR for RA was about 3 in first degree relatives of RA patients, and 2 in second degree relatives. The familial risks were similar among siblings (OR=3.6 (3.1-4.0)), parents (3.1 (2.9 -3.3)) and offspring (3.2 (3.0 - 3.5)). Familial aggregation was not modified by sex, but was higher for RA with early onset and for seropositive RA. The familial aggregation was most pronounced for ACPA+ disease, while the familiality of seronegative disease was similar as the cross-phenotype risks (Table). The observed familial risks were consistent with a heritability for ACPA+ RA of around 50% and for ACPA- RA of about 20%. <h3>Conclusions</h3> The pattern of risks suggests that familial factors influence RA in men and women equally, and that these factors are more important for early onset RA. Familial factors are more important for seropositive RA, but there is a significant familial overlap between seropositive and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest a heritability of RA lower than previously reported, in particular for ACPA- RA. <h3>Disclosure of Interest</h3> None Declared
Drug Pricing Gets Further Airing in Senate Hearing
Authors: K. Nagy
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Drug Pricing Gets Further Airing in Senate Hearing Get access Kate Nagy Kate Nagy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 6, 17 March 1993, Pages 432–433, https://doi.org/10.1093/jnci/85.6.432-a Published: 17 March 1993
B13
Authors: M. R. Starling, L. J. DellʼItalia, T. K. Chaudhuri, Bruce L. Boros, R. A. OʼRourke
Journal: Clinical Nuclear Medicine (1984)

Starling, M. R.; Dell'Italia, L. J.; Chaudhuri, T. K.; Boros, Bruce L.; O'Rourke, R. A. Author Information
Pathology of the Surfactant System of the Mature Lung
Authors: ROGER G. SPRAGG, JAMES F. LEWIS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Knowledge of the surfactant system has grown immensely in the past decade. A variety of investigative strategies, including manipulation of surfactant protein gene expression in mice, has contributed dramatically to our understanding of the role of surfactant components in lung function. These approaches have fostered investigations that will further our knowledge of the role of lung surfactant in host defense and will provide information that should lead to improved strategies for the treatment of lung disease.
AN ADOLESCENT WITH POSSIBLE TAKAYASU'S ARTERITIS, GIANT CORONARY ARTERY ANEURYSMS AND RECURRENT ACUTE CORONARY SYNDROME
Authors: Ashkan Karimi, Negiin Pourafshar, James Fudge, Arwa Saidi, Anthony Bavry, R. David Anderson, Ki Park, Mark Bleiweis, Diego Moguillansky
Journal: Journal of the American College of Cardiology (2016)
Complete remission with TKI in renal cell carcinomas: Experience in 65 patients of the French Kidney Cancer Group.
Authors: L. Albiges, S. Oudard, S. Negrier, A. Caty, G. Gravis, F. Joly, B. Duclos, L. Geoffrois, F. Rolland, B. Escudier
Journal: Journal of Clinical Oncology (2010)

4600 Background: Complete remission (CR) is uncommon with TKIs in metastatic renal cell carcinoma (mRCC), but may occur in few patients (pts). Currently, whether we should continue therapy after CR, is still a matter of debate. This study was conducted to provide some answers to the physicians. Methods: Through a questionnaire to the members of the French Group, we performed a multicentric retrospective analysis of a series of mRCC pts who developed CR under TKIs, either alone (sunitinib or sorafenib), or in combination with local treatment (surgery, radiotherapy or RFA). The following items were recorded: tumor histology, prior treatment, number and location of metastatic sites, prognostic group (according to the French Classification), duration of TKI treatment, nature and date of complementary local procedures, follow up after CR obtention. Results: CR was identified in 65 pts, 39 with TKI alone and 26 with the addition of local treatment. Most of the pts had clear cell histology (61/65), previous nephrectomy (64/65) and developed CR with sunitinib (61/65). CR occurred in 27 pts, 23 pts and 15 pts with 1, 2 or >2 metastatic sites respectively. Prognostic group was favorable in 22 pts, intermediate in 39 pts and poor in 4 pts. Among the 39 pts developing CR with TKI alone, 12 continued on TKI after CR, while 27 stopped TKI , in average 1 month after CR . For these 27 pts, 17 pts who stopped treatment are still in CR (63%) with a median follow up (FU) of 291 days. Among the 26 pts in CR after TKI plus local treatment, 23 pts stopped TKI after CR, and 15 of them are still in CR (65%) with a median FU of 322 days. Conclusions: CR can occur after TKIs alone or combined with local treatment. CR was observed in every metastatic site, in every prognostic group, even in poor risk. When a CR is obtained, the interruption of TKI is possible, with more than 60% pts remaining in CR. Data will be updated at the Meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, AVEO, GlaxoSmithKline, Novartis, Pfizer, Roche, Wyeth Bayer, GlaxoSmithKline, Novartis, Pfizer, Wyeth GlaxoSmithKline, Roche, Wyeth
COMPARATIVE EFFECT OF NOVAL ORAL ANTICOAGULANTS ON GLOBAL THROMBOTIC STATUS IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Mohamed Farag, Osita Okafor, Maria Niespialowska-Steuden, Benjamin Artman, Manivannan Srinivasan, Arif Khan, Diana Gorog
Journal: Journal of the American College of Cardiology (2015)
New German abortion law agreed
Authors: H. L Karcher
Journal: BMJ (1995)

The German Bundestag has passed a compromise abortion law that makes an abortion performed within the first three months of pregnancy an unlawful but unpunishable act if the woman has sought independent counseling first. Article 218 of the German penal code, which was established in 1871 under Otto von Bismarck, had allowed abortions for certain medical or ethical reasons. After the end of the first world war, the Social Democrats tried to legalize all abortions performed in the first three months of pregnancy, but failed. In 1974, abortion on demand during the first 12 weeks was declared legal and unpunishable under the social liberal coalition government of chancellor Willy Brandt; however, the same year, the German Federal Constitution Court in Karlsruhe ruled the bill was incompatible with article 2 of the constitution, which guarantees the right to life and freedom from bodily harm to everyone, including the unborn. The highest German court also ruled that a pregnant woman had to seek a second opinion from an independent doctor before undergoing an abortion. A new, extended article 218, which included a clause giving social indications, was passed by the Bundestag. When Germany was unified, East Germans agreed to be governed by all West German laws, except article 218. The Bundestag was given 2 years to revise the article; however, in 1993, the Federal Constitution Court rejected a version legalizing abortion in the first 3 months of the pregnancy if the woman sought counsel from an independent physician, and suggested the recent compromise passed by the Bundestag, the lower house of the German parliament. The upper house, the Bundesrat, where the Social Democrats are in the majority, still has to pass it. Under the bill passed by the Bundestag, national health insurance will pay for an abortion if the monthly income of the woman seeking the abortion falls under a certain limit.
Alternative maps of the world of collective behaviors
Authors: Robert J Maccoun
Journal: Behavioral and Brain Sciences (2014)

Abstract I compare the collective behavior map proposed by Bentley et al. (“BOB” for short) with a similar “balance of pressures” (BOP) map proposed by MacCoun (2012). The BOB and BOP maps have important points of convergence, but also some differences. The comparison suggests that they are analogous to different map “projections” for maps of Earth – different ways of simplifying a complex reality.
Comparison of transnasal small-caliber vs. peroral conventional esophagogastroduodenoscopy for evaluating varices in unsedated cirrhotic patients
Authors: W. Choe, J. Kim, S. Ko, S. Kwon, B. Kim, K. Rhee, T. Seo, T. Lee, S. Hong, S.-Y. Lee, I. Sung, H. Park, C. Shim
Journal: Endoscopy (2011)

See also: Commentaire de travail de W. H. Choe et al., pp. 649Endoscopy 2011; 43(08): 931-931DOI: 10.1055/s-0031-1291775