tbuckley/cabot-search huggingface dataset:
Abstract 5226: Understanding single cell variability in oncogene induced pathway aberration in lung cancer.
Authors: Dhruba Deb, Satwik Rajaram, Jill Larsen, John Minna, Lani Wu, Steven Altschuler
Journal: Cancer Research (2013)

Abstract Progression of normal epithelial cells towards malignancy is marked by alteration in signaling pathways involved in cellular growth and development. However, at any given stage of oncogenic progression, it is unknown to what extent different signaling pathways are altered and whether the degree of signaling change is similar from cell to cell. A quantitative survey of signaling alterations that are associated with common oncogenic changes will allow us to connect the widely observed signaling heterogeneity in cancer to the genetic changes leading to its disease states. Here, we study an isogenic series of human bronchial epithelial cells (HBECs) that have been oncogenically transformed with the sequential addition of common lung cancer mutations (p53null, p53null+KRASV12, p53null+KRASV12+c-myc). To quantify the degree of signaling alteration, we performed immuno-fluorescence assays and acquired images of HBECs stained with signaling markers representing important lung cancer pathways including WNT, JAK/STAT, TGFβ, IFNγ, MAPK, AKT and TNFα pathways. We extracted intensity-based features from individual cells using our in-house image analysis platform. This single-cell analysis revealed a high degree of signaling change within each of our HBEC populations, suggesting that signaling alteration can be different from cell to cell and from pathway to pathway. We further quantified the degree of pathway alteration along our sequential oncogenic manipulations by using standard machine learning techniques. Our analysis revealed significant changes in the WNT, TGFβ and MAPK pathways upon oncogenic progression. Loss of p53 alone caused a major shift in TGFβ signaling; addition of mutant KRASV12 altered the MAPK, TNFα and JAK/STAT pathways; Addition of a third genetic manipulation, C-MYC, induced dramatic shifts in the WNT and IFNγ pathways. We are currently in the process of inferring crosstalk among multiple pathways in HBECs and a panel of ten lung cancer cell lines. Taken together, our results suggest that the degree of signaling alteration across diverse signaling pathways can be correlated with a specific oncogenic state in lung cancer. Citation Format: Dhruba Deb, Satwik Rajaram, Jill Larsen, John Minna, Lani Wu, Steven Altschuler. Understanding single cell variability in oncogene induced pathway aberration in lung cancer. [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 5226. doi:10.1158/1538-7445.AM2013-5226
Evaluation of Persistent Edema with Lymphoscintigraphy After Femoral Artery Injury
Authors: NURIYE ÖZLEM KÜÇÜK, BURCU GÜLEV, GÜLSEREN ARAS, KEMAL METIN KR
Journal: Clinical Nuclear Medicine (2002)

KÜÇÜK, NURIYE ÖZLEM M.D.; GÜLEV, BURCU M.D.; ARAS, GÜLSEREN M.D.; KR, KEMAL METIN M.D.ı Author Information
Abstract 4188: Protein profiling of the first genetically engineered murine model of brainstem glioma
Authors: Javad Nazarian, Oren J. Becher, Yetrib Hathout, Tobey J. MacDonald
Journal: Cancer Research (2010)

Abstract Brainstem gliomas account for about 15% of all pediatric brain tumors and are the leading cause of death for pediatric brain cancers. The PDGFB induced mouse model of brainstem glioma (BSG) uses the RCAS/t-va system and is the first genetically engineered murine model of the disease. Tumors of these mice exhibit histopathological characteristics of pediatrics BSGs. Tumorigenesis is driven by overexpression of PDGFB in nestin expressing progenitors and accelerated by deletion of INK4A-ARF. Although PDGFB is known to be highly expressed both in these mice and a subset of pediatric BSGs, the exact mechanisms of disease formation and progression is not well understood. In an attempt to explore the molecular mechanisms of PDGFB-mediated tumor formation, we generated the complete protein profiles of brainstem samples obtained from normal (n=3) and PDGFB-induced BSG (N=3) mice. Total proteins were extracted, tryspin digested and resulting peptides were analyzed by shotgun proteomics (LC-MS/MS) and proteins were identified using Sequest algorithm. Label-free analysis was performed using ProteoIQ software. A total of 1,363 proteins were confidently identified by using the following stringent filtration criteria: &amp;gt; 2 peptides/protein, &amp;gt;10 spectra/protein, minimum peptide probability of 0.95, and a minimum peptide length of 5 amino acids. Our analysis identified overlap in several molecular pathways that we had previously reported in proteomic profiling of pediatric formalin fixed autopsy specimens. Some of the proteins that showed similar dysregulation included: ALDOC, EEF1A1, GPI, PKM2, and SPTBN1. Furthermore, the list of proteins and their expression values were analyzed by the Ingenuity Pathway Assist (IPA). IPA derives molecular interactions based on published data and peer-reviewed manuscripts. Our analysis showed that 228 of these proteins have been reported to play a role brain tumor or other types of cancer. Together, our protein analysis of the first murine model of BSG has provided significant additional insights regarding into PDGFB-induced oncogenesis and molecular perturbations. Our analysis is the first report of the comprehensive protein profile of this novel BSG murine model. Pathways and molecular interactions identified by this combined comparative proteomic approach will require further validation both using additional samples obtained from the murine BSG model as well as human postmortem BSG specimens. Such validations may lead to the identification of therapeutic targets and improve our understanding of the biology of BSG. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4188.
P17.03 * POST-OPERATIVE EXCLUSIVE CHEMOTHERAPY WITH PCV FOR ANAPLASTIC OLIGODENDROGLIOMA: A RETROSPECTIVE STUDY OF 35 CONFIRMED CASES
Authors: P. Augereau, A. Rousseau, S. Michalak, A. Pavageau, D. Loussouarn, E. Jadaud, E. Nader, P. Menei, P. Soulie
Journal: Neuro-Oncology (2014)

INTRODUCTION: Anaplastic oligodendroglioma/oligoastrocytoma (AO/AOA) represent among primary brain tumors a distinct chemosensitive heterogeneous entity with variable prognosis. New insights in biology have shown the prognostic impact of molecular/genomic tests (1p/19q status and IDH1 mutation). For many decades, front line therapy remains surgery followed by radiotherapy. In two recently updated large phase III trials, patients with 1p/19q codeleted tumors and/or IDH1 mutation lived longer after radiotherapy and adjuvant chemotherapy with PCV (Procarbazine, CCNU, Vincristine). Some authors suggest also encouraging outcome with chemotherapy alone with PCV or temozolomide. PATIENTS AND METHODS: We reviewed a serie of 54 patients initially diagnosed with AO or AOA, consecutively treated in a single center and who received PCV first after initial surgery. Radiation was delayed until relapse or when primary chemotherapy failed. All cases were retrospectively reviewed by a second neuropathologist and reclassified according the 2007 WHO criteria as well 1p/19q codeletion and IDH1 mutation were assessed when possible. RESULTS: From 10/2000 to 10/2009, 35 patients (out of 54) have confirmed diagnosis of AO (n = 25) or AOA (n = 10) and were considered for this analysis. Nineteen out of the 30 tested tumors (63%) had 1p/19q codeletion and 27/35 were IDH1 mutated (by IHC). Follow up MRI were scheduled every 3 months. Sixty-seven% of patients were younger than 50 years, 88% had a resection and 100% had a PS 0 or 1. Median number of delivered cycles was 4 (1 to 6) with hematological toxicity being the main cause of early interruption. The median follow-up was 54,7 months [95% CI; 4,7-17,8]. Median PFS and OS were 51,9 months [36,7 to NR] and 89,5 months [61,1 to NR] respectively in all AO/AOA. In the codeleted subgroup, median PFS was not reached [47,2-NR] and OS was 89,5 months [69,5 - NR]. In the non codeleted, median PFS and OS were shorter (11,6 and 39 months). In the IDH1 mutated subgroup, OS and PFS were respectively 89,5 [68,1 to NR] and 51,9 [37,3 to NR] months respectively. For patients with the wild type IDH1, OS and PFS were lower: 32 [6,7 to NR] and 18,7 [2,9 to NR] months. As of February 2014, eleven patients (31%, 10 codeleted tumors, 8 IDH1 mutated) with no disease progression, after a median follow up of 63,3 months, have not yet received salvage radiotherapy. CONCLUSION: Our results produce additional data to support a personalized treatment strategy for AO/AOA based on molecular/genomic analysis. However, omission of adjuvant RT in order to reduce the risk of delayed neurocognitive dysfunctions could not be recommended and should be implemented in clinical trials.
Closing the Books on Laetrile
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1982)

Over the past few years we have devoted a lot of attention to Laetrile.1 2 3 4 5 6 7 By 1978 it had achieved a certain folk status, celebrated as a kind of anti-establishment natural remedy being suppressed by a venal conspiracy between pharmaceutical manufacturers and physicians. According to the folklore, the conspirators were ignoring evidence of Laetrile's effectiveness and attempting to promote their own more orthodox (and more toxic) forms of cancer chemotherapy.There have never been any facts to support this folklore, but that didn't prevent tens of thousands of American cancer victims from seeking treatment with Laetrile — often obtaining it at . . .
Augmented Post-Induction Therapy for Children with High-Risk Acute Lymphoblastic Leukemia and a Slow Response to Initial Therapy
Authors: James B. Nachman, Harland N. Sather, Martha G. Sensel, Michael E. Trigg, Joel M. Cherlow, John N. Lukens, Lawrence Wolff, Fatih M. Uckun, Paul S. Gaynon
Journal: New England Journal of Medicine (1998)

Children with high-risk acute lymphoblastic leukemia (ALL) who have a slow response to initial chemotherapy (more than 25 percent blasts in the bone marrow on day 7) have a poor outcome despite intensive therapy. We conducted a randomized trial in which such patients were treated with either an augmented intensive regimen of post-induction chemotherapy or a standard regimen of intensive post-induction chemotherapy.
Abstract 1668: Induction of Autophagy by a novel agent promotes the growth arrest in breast cancer cells.
Authors: Ramadevi Subramani Reddy, Pallab Pahari, Chendil Damodaran
Journal: Cancer Research (2013)

Abstract Breast cancer is a highly complex disease due to its heterogeneity in nature; that often impedes the current therapeutic options. Autophagy is a catabolic process which plays a vital role in both progressions as well as in the treatment of cancer. In fact, the role of autophagy in cancer is still unclear. Our lab is focusing on small molecules, which may induce autophagy that may result in growth arrest in breast cancer cells. In our preliminary screening studies, we have identified a small molecule, Nimocinol Acetate (NA) which induces autophagy that resulted in inhibition of growth of estrogen-positive (MCF-7) and estrogen-negative (MDA-MB-231) breast cancer cells. Molecular analysis showed the significant induction of LC-3B and ATG-3 in NA treated cells as compared to other autophagy-regulators like Atg5, Atg7, Atg12, and beclin-1, which convey the importance of ATG3 and LC3B markers in induction of autophagy. The immunofluorescence analysis confirmed the formation of acidic autophagic vesicles upon NA treatment. To further ascertain the involvement of lysosomes and autophagosomes, we specifically blocked ATG-3 and LC-3B expression by siRNA and then subjected to immunofluorescence assay. The observed results confirmed the contribution and activation of these two molecules is required for the induction of autophagy. Interestingly, no significant changes were obseverved either in the cell cycle regulation or in induction of apoptosis, which revealed that the activation of autophagy may be responsible for NA mediated growth inhibition in breast cancer cells. Currently, we are planning to conduct xenograft studies, which may suggest the in vivo efficacy and pharmacokinetic potential of NA. The present study concludes that NA could be a potential agent either alone or in combination with other chemotherapeutic agents with a novel strategy to combat breast cancer. Citation Format: Ramadevi Subramani Reddy, Pallab Pahari, Chendil Damodaran. Induction of Autophagy by a novel agent promotes the growth arrest in breast cancer cells. [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 1668. doi:10.1158/1538-7445.AM2013-1668
Abstract 3083: A novel method of sonic hedgehog signaling activation in the chemoresistance of glioblastoma: A ligand-independent mechanism.
Authors: Jessian L. Munoz, Pranela Rameshwar
Journal: Cancer Research (2013)

Abstract Glioblastoma Multiforme (GMB) is the most common and lethal adult primary tumor of the central nervous system. Despite current chemotherapy with concomitant surgical resection and radiotherapy, GBM 5-year survival is ∼3%. A better understanding of the cellular pathways in tumor proliferation and survival is required for the development of new treatments. Previously, the Sonic Hedgehog pathway has been shown to be dysregulated in chemoresistant GBM. Pharmacological inhibition of SHH signaling with Cyclopamine enhanced GBM chemosensitivity to temozolomide (TMZ). SHH receptor, PTCH1, is tonically repressed by the ligandbut is activated by by receptor-mediated endocytosis of SHH. Here we show SHH signaling in GBM is ligand-independent and is initiated by post-transcriptional regulation of PTCH1. MicroRNA are small non-coding RNA molecules known to regulate a number of cell processes such as development and oncogenesis. As far as we are aware there is no report on microRNA in the regulation of PTCH1. Knockdown of Dicer, a Type III RNAase, which is required for microRNA synthesis, increased the cellular toxicity to TMZ, thus revealing the importance of microRNA in GBM chemoresistance. We have indentified and characterized PTCH as a functional target of microRNA-9 (miR-9) in both non-neural cell lines as well as GBM cell lines. Overexpression of miR-9 in GBM cells results in downstream pathway activation and resistance to TMZ treatment. We also explored a number of mir-9/PTCH1-dependent mechanisms of chemoresistance and uncovered downstream upregulation of ATP-binding cassette drug efflux transporters, MDR1 and ABCG2. Taken together, our data indicate a role for miRNA9 in the acquisition of chemoresistance in GBMs and may serve as novel therapeutic targets. Citation Format: Jessian L. Munoz, Pranela Rameshwar. A novel method of sonic hedgehog signaling activation in the chemoresistance of glioblastoma: A ligand-independent mechanism. [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 3083. doi:10.1158/1538-7445.AM2013-3083
Tl-201 Uptake in Reactive Lymphadenopathy
Authors: SCOTT M. DUNKLEY, PAUL J. ROACH
Journal: Clinical Nuclear Medicine (1997)

Differentiation of infective from neoplastic lesions is problematic when using Ga-67 citrate as both conditions may show uptake of this radiopharmaceutical. In contrast, although Tl-201 chloride uptake is often shown in tumors, avidity is found far less in inflammatory or infective lesions. A 44-year-old man had reactive lymphadenopathy secondary to salmonella typhii septicaemia. Although lesions in two sites showed the typical appearance of Ga-67 avidity with only mild Tl-201 uptake, biopsy confirmed that reactive changes in the left inguinal nodes were seen on Tl-201. However, these changes were not seen in Ga-67 scintigraphy, which was an unexpected finding.
Characterizing the Peroxisome Proliferator-Activated Receptor (PPAR <b>γ</b> ) Ligand Binding Potential of Several Major Flame Retardants, Their Metabolites, and Chemical Mixtures in House Dust
Authors: Mingliang Fang, Thomas F. Webster, P. Lee Ferguson, Heather M. Stapleton
Journal: Environmental Health Perspectives (2014)

Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor.Our goal was to determine the PPARγ ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding activity of indoor dust and its bioactivated extracts were also investigated.We used a commercially available fluorescence polarization ligand binding assay to investigate the binding potency of flame retardants and dust extracts to human PPARγ ligand-binding domain. Rosiglitazone was used as a positive control.Most of the tested compounds exhibited dose-dependent binding to PPARγ. Mono(2-ethylhexyl) tetrabromophthalate, halogenated bisphenols and phenols, and hydroxylated PBDEs were found to be potent PPARγ ligands. The most potent compound was 3-OH-BDE-47, with an IC50 (concentration required to reduce effect by 50%) of 0.24 μM. The extent of halogenation and the position of the hydroxyl group strongly affected binding. In the dust samples, 21 of the 24 samples tested showed significant binding potency at a concentration of 3 mg dust equivalent (DEQ)/mL. A 3-16% increase in PPARγ binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions.Our results suggest that several flame retardants are potential PPARγ ligands and that metabolism may lead to increased binding affinity. The PPARγ binding activity of house dust extracts at levels comparable to human exposure warrants further studies into agonistic or antagonistic activities and their potential health effects.
AB0192 Can anti-ccp antibody titer predict the use of biologics ?
Authors: R. Rokutanda, M. Kishimoto, K. Yamaguchi, H. Shimizu, Y. Suyama, Y. Ohara, Y. Haji, C. Min, A. Takeda, Y. Matsui, M. Okada, K. Nishioka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-CCP antibody (ACPA) is widely used for diagnosis of rheumatoid arthritis (RA), and ACPA seropositivity has been known as a factor associated with a poor joint prognosis. However, the importance of ACPA titer, especially its influence for treatment decision, remains unclear. <h3>Objectives</h3> The purpose of this study is to analyze whether RA patients with higher ACPA titer need biologics more frequently or not. <h3>Methods</h3> We extracted all the RA patients who underwent ACPA test during the period from February 2012 to October 2012. These patients were divided into three groups based on the value of ACPA, e.g. negative (less than 4.5 U/mL), positive (4.5-100 U/mL), and strong positive (more than 100 U/mL). We retrospectively reviewed all the biologic/non-biologic DMARDs the patients had ever used, and compared the rates of biologics use among three groups. <h3>Results</h3> The rate of biologic use was significantly lower in negative ACPA group (31.0%) compared to positive ACPA group (55.6%, p&lt;0.05) or strong positive ACPA group (67.9%, p&lt;0.05, Table 1). Among ACPA positive patients, strong ACPA group tend to use biologics more frequently. The rate of patients without biologics nor MTX was significantly higher in negative ACPA group (34.5%) than in ACPA positive group (8.3%, p&lt;0.05) or strong positive ACPA group (5.1%, p&lt;0.05). <h3>Image/graph</h3> <h3>Conclusions</h3> Not only the ACPA positivity but also high ACPA titer can be predictors for biologics use in RA patients. <h3>Disclosure of Interest</h3> None Declared
Upper gastrointestinal endoscopic ultrasonography analysis and evaluation of clinical epidemiology
Authors: Zheng-xiang Wu, Ming-li Zhang, Zuo Wang, Kai-guang Zhang, Xi-ping Ding, Mei-zhi Wei, Qiao-ming Wang
Journal: Endoscopy (2011)

Methods: Collected 3032 cases of sub-cases of upper gastrointestinal EUS, analysis characteristics of EUS and test results, using epidemiological methods to forward-looking assessment the value of EUS.
FASEB Panel Escalates Debate About IOM Training Recommendations
Authors: R. Scott
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article FASEB Panel Escalates Debate About IOM Training Recommendations Get access Robert Scott Robert Scott Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 1, 2 January 1991, Pages 4–5, https://doi.org/10.1093/jnci/83.1.4 Published: 02 January 1991
Management of a case of neuroleptic malignant syndrome with bromocriptine
Authors: G Zubenko, H G Pope
Journal: American Journal of Psychiatry (1983)

Neuroleptic malignant syndrome, a rare but potentially fatal side effect of antipsychotic medications, has often proven refractory to conventional antiparkinsonian medications. The authors report a dramatic response of this syndrome to the dopamine agonist bromocriptine mesylate in a patient receiving fluphenazine decanoate.
Understanding variation in utilisation: start with health needs
Authors: M. A. Soljak, A. Majeed
Journal: BMJ (2013)

In their paper on the effect of illness adjustment on regional mortality and spending rates using standard and visit corrected illness methods for adjustment, Wennberg and colleagues compare adjustment using diagnoses listed in administrative databases with additional adjustment for the frequency of doctors’ visits.1 They acknowledge that data on the use of healthcare cannot be used directly as a proxy for need or risk because these data also reflect differences in access to …
GW25-e3420 Plasma NT pro-BNP, hs-CRP and big-ET levels at admission as prognostic markers of survival in hospitalized patients with dilated cardiomyopathy: a single-center cohort study
Authors: Li Xiaoping, Chengzhi Chen, Feng Gan, Yang Wang, Ligang Ding, Wei Hua
Journal: Journal of the American College of Cardiology (2014)
Intestinal Absorption of Bile Pigments
Authors: Roger Lester, Rudi Schmid
Journal: New England Journal of Medicine (1963)

IN the voluminous literature on bile-pigment metabolism1 little attention has been given to the possibility that bilirubin is reabsorbed from the intestinal tract. Recent studies utilizing G14-labeled pigment2 have demonstrated that unconjugated bilirubin is absorbed rapidly from the intestine of rats. In contrast conjugate is not absorbed intact,2 hepatic conjugation creating a barrier against the reabsorption of the potentially toxic3 unconjugated pigment. In rats this conjugate barrier is incomplete; a fraction of the administered bilirubin glucuronide is hydrolyzed in the intestine, and significant quantities of the released unconjugated bilirubin are absorbed.The following studies were performed to determine whether . . .
Imatinib mesylate directly impairs class switch recombination through down-regulation of AID: its potential efficacy as an AID suppressor
Authors: Toyotaka Kawamata, Jun Lu, Tadayuki Sato, Masafumi Tanaka, Hitoshi Nagaoka, Yasutoshi Agata, Takae Toyoshima, Kazuaki Yokoyama, Naoki Oyaizu, Naoya Nakamura, Kiyoshi Ando, Arinobu Tojo, Ai Kotani
Journal: Blood (2012)