tbuckley/cabot-search huggingface dataset:
Abstract 225: Protein tyrosine kinase 6 directly phosphorylates p130 CRK-associated substrate to promote peripheral adhesion complex formation and cell migration
Authors: Yu Zheng, Angela L. Tyner
Journal: Cancer Research (2012)

Abstract Protein tyrosine kinase 6 (PTK6) is a nonmyristoylated intracellular tyrosine kinase evolutionarily related to Src kinases. Aberrant PTK6 expression and intracellular localization have been detected in human prostate tumors. Although the majority of total PTK6 is localized within the cytoplasm of PC3 cells, a human prostate cancer cell line, we found that the activated pool of PTK6 phosphorylated on tyrosine residue 342 is localized at the membrane. Ectopic expression of membrane targeted PTK6 leads to enhanced activation of PTK6 at the membrane and the formation of 6 to 12 striking focal adhesion-like complexes localized at the periphery of each cell, termed peripheral adhesion complexes. Using confocal microscopy, we show that p130 CRK-Associated Substrate (p130CAS), FAK, Paxillin and Vinculin, as well as increased levels of tyrosine phosphorylated proteins and active PTK6 are localized within the induced peripheral adhesion complexes. We determined that peripheral adhesion complex formation is dependent upon PTK6 tyrosine kinase activity. We demonstrate that p130CAS is a novel direct substrate of PTK6 that works as a crucial adapter protein in PTK6 mediated formation of peripheral adhesion complexes. We found that activation of ERK5 signaling downstream of p130CAS is indispensible for this process. Knockdown of p130CAS attenuates oncogenic signaling induced by membrane targeted PTK6, including ERK5 and AKT activation. We show that formation of peripheral adhesion complexes is associated with enhanced cell migration. PC3 cells expressing membrane targeted PTK6 exhibit increased migratory ability, which can be impaired by knockdown of p130CAS or ERK5. In contrast, knockdown of endogenous PTK6 in PC3 cells reduces cell migration, which is accompanied with decreased phosphorylation of p130CAS and ERK5. Our study reveals a novel function for PTK6 at the plasma membrane, and suggests that a PTK6-p130CAS-ERK5 signaling cascade plays an important role in cancer cell migration and invasion. 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 225. doi:1538-7445.AM2012-225
The Treatment of Wringer-Arm Injuries
Authors: Donald W. MacCollum, William F. Bernhard, Robert L. Banner
Journal: New England Journal of Medicine (1952)

THE term, "wringer arm," was first coined in 1938§ to describe an accident occurring in early childhood in which the upper extremity is inadvertently caught between the rollers of a power-driven washing-machine wringer. In addition to 26 cases previously reported, 116 children with this injury have been treated at the Children's Medical Center, Boston, from 1937 through 1951. In recent years there seems to have been a marked decrease in the incidence of this type of accident, probably owing to the perfection of emergency-release devices on automatic wringer machines and to the wider use of machines equipped with a centrifugal . . .
SENSORY DEPRIVATION
Authors: PHILIP SOLOMON, P. HERBERT LEIDERMAN, JACK MENDELSON, DONALD WEXLER
Journal: American Journal of Psychiatry (1957)

Sensory deprivation has been produced experimentally by reducing the absolute intensity of stimuli, by reducing the patterning of stimuli, and by imposing a structuring of stimuli. Explorers have experienced it voluntarily and prisoners have had it thrust upon them. While there are many separate factors operating in these various situations, it is clear that the stability of man's mental state is dependent on adequate perceptual contact with the outside world. Observations have shown the following common features in cases of sensory deprivation: intense desire for extrinsic sensory stimuli and bodily motion, increased suggestibility, impairment of organized thinking, oppression and depression, and, in extreme cases, hallucinations, delusions, and confusion. Though the basic concepts regarding perceptual and sensory deprivation are not new, their recent importance in experimental and real life situations has made them increasingly interesting. Future studies in this area may well contribute to our knowledge of the psychological and behavioral patterns of man under conditions of normality and stress.
Improved Survival from Acute Renal Failure after Treatment with Intravenous Essential L-Amino Acids and Glucose
Authors: Ronald M. Abel, Clyde H. Beck, William M. Abbott, John A. Ryan, G. Octo Barnett, Josef E. Fischer
Journal: New England Journal of Medicine (1973)

Original Article from The New England Journal of Medicine — Improved Survival from Acute Renal Failure after Treatment with Intravenous Essential L-Amino Acids and Glucose — Results of a Prospective, Double-Blind Study
Abstract 2179: Bile acids downregulate the squamous differentiation program of esophageal cells
Authors: Marie Reveiller, Sayak Ghatak, Irina Kalatskaya, Liana Toia, Mary DSouza, Zhongren Zhou, Santhoshi Bandla, Tony E. Godfrey, Jeffrey Peters
Journal: Cancer Research (2011)

Abstract Background: The lumen of the normal esophagus is covered by a nonkeratinized, stratified squamous epithelium. However, in individuals with prolonged gastroesophageal reflux disease the squamous epithelium is gradually replaced by a more acid-resistant metaplastic columnar epithelium known as Barrett's Esophagus (BE). BE is the strongest known risk factor for development of esophageal adenocarcinoma. Understanding the molecular mechanisms underlying the formation of BE is fundamental to the development of new and effective prevention and treatment strategies for patients with BE. Methods: We performed a global analysis of gene expression in normal squamous esophageal cells in response to bile acids or acid exposure. Differentially expressed genes were classified into major biological functions based on analysis using pathway and interaction network software programs. Array data were verified by quantitative PCR and western blot both in-vitro and in human biopsies from esophageal normal squamous and columnar epithelia. Results: Bile acids modulated expression of 218 genes (153 up and 65 down) and acid 112 genes (31 up and 81 down). Interestingly, genes involved in squamous differentiation formed the largest functional group of differentially expressed genes and consisted of 40 genes downregulated by bile acids exposure. Bile acids decreased expression of key squamous differentiation genes such as KRT10, KRTDAP and GRHL1 which was confirmed at both the mRNA and protein level as was increased expression of CDX2, a transcription factor key to the intestinal epithelial phenotype. Bile acids induced expression changes were also seen in genes involved in the pathways of cell adhesion, DNA repair, oxidative stress, cell cycle, Wnt signaling and lipid metabolism. Expression of DSG1, a target gene of GRHL1, and DKK1, a Wnt inhibitor, were confirmed to be respectively downregulated and upregulated by bile acids. Further, expression data from human columnar epithelial biopsies revealed low or no expression of KRT10, KRTDAP, DSG1 and GRHL1 compared to squamous epithelia. Finally, network analysis suggested that bile acids exposure modulated the transcription activity of CREB and bile acids induced phosphorylation of CREB was confirmed experimentally. Conclusion: We report for the first time that bile acids inhibit the squamous differentiation program of esophageal cells while inducing columnar differentiation via CDX2 expression possibly via CREB and Wnt signaling. 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 2179. doi:10.1158/1538-7445.AM2011-2179
QL-01 * ANXIETY, DEPRESSION AND ANGER IN CHILDREN WITH EPENDYMOMA: A REPORT FROM THE COLLABORATIVE EPENDYMOMA RESEARCH NETWORK (CERN) PEDIATRIC OUTCOMES PROJECT (PEO)
Authors: A. Acquaye, E. Vera-Bolanos, M. R. Gilbert, T. S. Armstrong
Journal: Neuro-Oncology (2014)

BACKGROUND: Ependymomas are relatively uncommon primary brain tumors in children. CERN is a multi-institutional group with the mission to develop new treatments, improve outcomes and care of patients. METHODS: The PEO study has an online survey completed by child/parent dyads which includes validated questionnaires, including PROMIS anxiety, depression and anger short-forms. Descriptive statistics were used to report the characteristics and degree of depression, anxiety and anger reported by the children versus their parents. Pearson's correlations, paired samples and independent samples t-tests were used to determine relationships and differences among variables of interest. RESULTS: Nineteen dyads (parent-child) participated including both boys (n = 10) and girls (n = 9). Ages ranged from 5-20 years (median =10). Tumors were primarily supratentorial (n = 11), with nearly all had received radiation, and nearly half having had recurrence (n = 9). There was no rating difference between boys and girls in terms of anxiety (p < 0.10) or depression (p < 0.83). There was a strong, positive correlation between the child's rating and parent's rating of anxiety (r = 0.71; p < 0.02), depression (r = 0.71; p < 0.02) and anger (r = .66; p < .02). However, there was a significant difference between the severity of depression between child and the parent report; parents rating their child's depression as more severe (mean = 10) than the child (mean = 7) (t = -2.4, df = 14, p < 0.03). Differences in anger ratings between parent and child approached significance (t = -2.0, df = 14, p = 0.07), with children reporting more anger. CONCLUSION: While parents rated anxiety similar to the child's, parents rated depression worse and anger less severe than the children themselves. This underscores the importance of assessing and managing psychological symptoms that arise including the input of both the child and parent to assure all needs are met.
Older females are at higher risk for medical complications during 21 km road race running: a prospective study in 39 511 race starters—SAFER study III
Authors: Karen Schwabe, Martin P Schwellnus, Wayne Derman, Sonja Swanevelder, Esme Jordaan
Journal: British Journal of Sports Medicine (2014)

Background The half-marathon (21 km) race is a very popular mass community-based distance running event. It is important to determine risk factors for medical complications during these events, so that prevention programmes can be developed. Objective To determine risk factors associated with medical complications during 21 km road running events. Design Prospective study. Setting Two Oceans half-marathon (21 km) races. Participants 39 511 starters in the 21 km race. Methods Medical complications (defined as any runner requiring assessment by a doctor at the race medical facility or a local hospital on race day) were recorded over a 4-year study period. Medical complications were subdivided according to the system affected and by final diagnosis. A Poisson regression model was used to determine risk factors for any medical complication and more common specific complications. Results Independent risk factors for medical complication during 21 km running were older female runners (women &gt;50 vs ≤50 years; p&lt;0.0001) and year of observation (2008 vs 2011; p=0.0201: 2009 vs 2011: p=0.0019; 2010 vs 2011: p=0.0096). Independent risk factors for specific common medical complications were: postural hypotension (women, slow running pace), musculoskeletal complications (less running experience, slower running pace) and dermatological complications (women). Conclusions Older female runners are at higher risk of developing medical complications during 21 km road running races. Environmental conditions in a particularly cold climate may also play a role. Less running experience and slower running pace are associated with specific medical complications. Medical staff can now plan appropriate care on race days, and interventions can be developed to reduce the risk of medical complications in 21 km races.
Abstract P1-01-24: Which combinations are helpful to predict axillary lymph node metastasis in T1 breast cancer with ultrasonography and contrast-enhanced MRI and contrast-enhanced 18F-FDG PET-CT?
Authors: SO Hwang, HY Park, JH Jung, WW Kim, YH Lee, JJ Lee, HH Choi, SM Hwangbo
Journal: Cancer Research (2012)

Abstract Backgrounds: Axillary lymph node(ALN) status has been important factor of treatment and prognosis for patients with breast cancer. Even though the better ultrasonographic instruments have been developed, it is still difficult to predict axillary lymh node metastasis (ALNM) with only ultrasonography(US) in T1 breast cancers which most of newly diagnosed breast cancers are recently since T1 breast cancers have low rate and less tumor burden of ALNM. This study evaluated the accuracy of prediction of ALNM in T1 breast cancer with US, contrast-enhanced MRI (cMRI) and contrast-enhanced 18F-FDG PET/CT (cPET/CT) and found out adequate combinations of these modalities. Method: Retrospectively, we reviewed 351 breast cancer patients with tumors(T1) ≤2cm in size between January 2008 and December 2011 who were preoperatively examined with US, cMRI, and cPET/CT and underwent pathologic evaluation of axillary lymph nodes acquired by sentinel lymph node biopsy or axillary dissection. Results: 94(26.8%) patients of 351 had ALNM. The sensitivity, specificity, positive predictive value(PPV), negative predictive value (NPV), and accuracy of ALNM with US were 0.457, 0.887, 0.597, 0.817, 0.772, respectively. cMRI had similar results with US. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ALNM with cPET/CT were 0.447, 0.942, 0.737, 0.823, 0.809, respectively. The sensitivity if any one or more modalities were suspicious was 0.563. The specificity if all modalities were suspicious was 0.992. The PPV if cMRI and cPET/CT were suspicious was highest than if other combinations were suspicious. Conclusion: US, cMRI, and cPET/CT are helpful in prediction of ALNM of T1 breast cancers. However, there are no definite modality and combination of modalites to predict ALNM of T1 breast cancers. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-24.
Abstract 2154: Molecular allelo-karyotyping of pulmonary adenocarcinoma using high resolution single nucleotide polymorphism genomic arrays
Authors: Hironori Ninomiya, Motohiro Kato, Kengo Takeuchi, Hiroaki Kanda, Sakae Okumura, Seishi Ogawa, Yuichi Ishikawa
Journal: Cancer Research (2010)

Abstract Background Lung cancer is the leading cause of cancer death in Japan. Adenocarcinoma is the most common form of lung cancer with poor-prognosis due to late-stage detection and resistance to conventional treatment. The complexity of the genetic alterations confer pulmonary adenocarcinomas with marked patterns of gene expression. It is now critical to unravel the mechanisms which underlie a subset of tumor and they should have a significant impact in selecting patients for targeted therapy. Novel SNP-chip high resolution molecular allelo-karyotyping analysis allows us to examine global DNA copy number changes and allelic loss to evaluate allele-specific gene dosage in cancer cells. Methods A series of consecutive 111 lung adenocarcinomas, including 10 cases harboring EML4-ALK fusion, were analyzed using Affymetrix GeneChip and our robust algorithm, CNAG/AsCNAR, to perform sensitive analysis of copy number alteration and allelic composition. This robust algorithm also enabled sensitive detection of loss of heterozygosity. Clinicopathological profiles including age, gender, smoking status, WHO histology subtypes, pathological stage and clinical outcome were also examined. Genomic profiles in the selected amplified and deleted regions were obtained. Results Chromosomal arm gains of 1q, 3q, 5p, 6p, 7p, 8q, 16p and 17q were detected, while frequent loss was found in 1p, 3p, 6q, 8p, 9p, 10q and 17p. Gene alteration profiles of known oncogenes and tumor suppressor genes were obtained with this procedure. Highly amplified regions included TERT (61.3%), MYC (45.9%), EGFR (44.1%), TNFSF6B (44.1%). Homozygous deletion was noted only in 9p23.3 (5.4%, CDKN2A, CDKN2B). Cases with EML4-ALK fusion were found to be less amplified in top 15 selected regions. Lymphatic invasion positive cases revealed distinct genomic profiles compared to negative ones. Conclusion Global analysis of gene expression using high resolution SNP genomic arrays can provide a broader view of genomic alterations. Genomic amplification and loss profiles differ according to clinicopathological aspects and genomic background. 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 2154.
Abstract 3733: Heregulin as a novel resistant factor for cetuximab
Authors: Kimio Yonesaka, Isamu Okamoto, Taroh Satoh, Kohji Takeda, Minoru Takada, Kazuto Nishio, Masahiro Fukuoka, Pasi A. Janne, Kazuhiko Nakagawa
Journal: Cancer Research (2010)

Abstract Background Epidermal growth factor receptor (EGFR) is a therapeutic target in colorectal cancer (CRC). Patients with CRC with wild type KRAS have significant tumor regressions with cetuximab. However cancers ultimately acquire resistance. The mechanisms of these are still unknown. We investigated mechanisms of acquired resistance to cetuximab. Methods The cetuximab-resistance cell line, A431ER, was established from cetuximab-sensitive parent A431 by exposing cetuximab. In vitro sensitivity was analyzed using MTS assay. Expression of ErbBs and heregulin (HRG) was analyzed with RTK array, immunoblotting (IB) and ELISA. Plasma samples were studied using ELISA among 44 pts with CRC, treated with cetuximab. Result A431 was so sensitive to cetuximab that the growth inhibition following 10μg/ml cetuximab (GI10) was about 50% in MTS. In contrast, A431ER was completely resistance (GI10 &amp;lt;10%). The RTK array showed that A431ER but not A431 had markedly phosphorylated ErbB2 and 3. Although ErbB2 and 3 were highly phosphorylated in A431ER, total protein level of those was equivalent to A431 in IB. Finally heregulin, a ligand for ErbB3, was detected significantly higher in A431 than A431ER using IB and also ELISA in culture mediums (355 vs 1025pg/ml). HRG inhibition with siRNA could restore the sensitivity to cetuximab in A431ER. And exogenous HRG induced A431 parent cell line resistant to cetuximab. The exogenous HRG also phosphorylated both Erb2 and 3 in A431, which means hetero-dimerization of those. So we did MTS assay with cetuximab and pertuzumab, which inhibited hetero-dimerization between ErbB2 and 3. Cetuximab alone or pertuzumab alone minimally effected in A431ER (GI10 was about 10%). But the combination of two drugs abundantly effected (GI10 was about 60%). About clinical samples, pts with progressive disease (PD, n=23) following cetuximab had higher expression of HRG in plasma than pts with non-PD (n=15) (median 1188 vs 4854pg/ml, p=0.0008). And low HRG group (&amp;lt;2000pg/ml, n=22) had longer progression free survival (HR 0.2371 (95%CI 0.095-0.593), p=0.0021) and overall survival (HR 0.2274 (0.075-0.693), p=0.0092) than high HRG group (&amp;gt;2000pg/ml, n=22). Finally, post- treatment samples had significantly higher HRG than pre-treatment in 6 pts, who acquired resistance after 5 months treatment (mean 904 vs 1890pg/ml, p=0.0161). Conclusion Our findings suggest that HRG could lead both de novo and acquired resistance to cetuximab. HRG-ErbB3-ErbB2 complex is a warranted target for overcoming resistance to cetuximab. 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 3733.
The Transjugular Intrahepatic Portosystemic Stent-Shunt Procedure for Variceal Bleeding
Authors: Martin Rossle, Klaus Haag, Andreas Ochs, Markus Sellinger, Gerd Noldge, Jean-Marc Perarnau, Elisabeth Berger, Uli Blum, Andreas Gabelmann, Karlheinz Hauenstein, Michael Langer, Wolfgang Gerok
Journal: New England Journal of Medicine (1994)

Transjugular placement of an intrahepatic stent is a new technique to establish a portosystemic shunt for treatment of portal hypertension. A puncture needle is advanced in a catheter through the inferior vena cava into a hepatic vein; then an intrahepatic branch of the portal vein is punctured and an expandable stent of metallic mesh is implanted to establish the shunt.We attempted the stent-shunt procedure in 100 of 112 consecutive patients with variceal bleeding due to cirrhosis, who were then followed for a mean (+/- SD) of 12 +/- 6 months. Of the 100 patients, 22 had Child-Pugh class C cirrhosis, 10 were treated on an emergency basis, and 68 had alcoholic cirrhosis. The shunt was established with use of Palmaz stents expanded to 8 to 12 mm in diameter.Technical success was achieved in 93 percent of the patients. The mean (+/- SD) time for the procedure was 1.2 +/- 0.3 hours. The shunt reduced the portal venous pressure gradient by 57 percent. Major complications were hemorrhage (intraabdominal bleeding in six patients, biliary bleeding in four, and bleeding in the liver capsule in three) and migration of the stent into the pulmonary artery (in two patients). At follow-up, stenosis of the shunt was evident in 21 patients and occlusion in 10 patients; 10 of these 31 patients had variceal rebleeding. Stenoses and occlusions of the shunt were all treated successfully by redilation, thrombolysis, or implantation of an additional stent. Hepatic encephalopathy (stages I to III) developed in 25 percent of the patients. The proportion of patients with shunts who remained free of variceal rebleeding was 92 percent at six months and 82 percent at one year. The 30-day mortality was 3 percent. The cumulative one-year survival was 85 percent.These results suggest that the transjugular placement of an intrahepatic portosystemic stent is an effective and safe treatment for variceal hemorrhage in patients with portal hypertension due to cirrhosis.