tbuckley/cabot-search huggingface dataset:
Abstract 2862: Bioengineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis
Authors: Hiroshi Tazawa, Shuya Yano, Ryosuke Yoshida, Yasuo Urata, Toshiyoshi Fujiwara
Journal: Cancer Research (2011)

Abstract Autophagy is known to have a cytoprotective role under various cellular stresses, such as deprivation of nutrients, hypoxia and interruption of growth signaling. In contrast, autophagy also results in robust cell death as an important safeguard mechanism that protects the organism against invading pathogens and unwanted cancer cells. Recent accumulating evidences have suggested the implication of autophagy on the oncolytic adenovirus-mediated cell death in human cancer cells. However, the molecular mechanism underlying oncolytic adenovirus-mediated autophagic cell death remains unclear. We previously generated a genetically engineered oncolytic adenovirus (Telomelysin®: OBP-301) that replicates and induces autophagic cell death against human cancer cells in a telomerase-dependent manner. As microRNA (miRNA), a post-transcriptional regulator of gene expression, has been recently shown to regulate diverse cell fates including autophagy, we hypothesized that OBP-301 infection induces autophagic cell death through miRNA modulation in human cancer cells. In this study, we attempted the role of miRNA on the OBP-301-mediated autophagic cell death in human cancer cells. We used 3 human cancer cell lines (H1299, A549 and T.Tn), that showed different sensitivities to OBP-301. OBP-301 infection upregulated miR-7 expression in OBP-301-sensitive human cancer cell lines (H1299 and A549), but not OBP-301-resistant human cancer cell line (T.Tn). Expression levels of miR-7 upregulated after OBP-301 infection was significantly associated with OBP-301-mediated cytopathic activity and autophagic cell death, which was confirmed by western blot for autophagy-related proteins (LC3-I/II, Atg5 and p62). We also revealed that OBP-301-mediated miR-7 upregulation mainly depended on enhanced expression of the E2F1 protein after OBP-301 infection. Furthermore, ectopic expression of miR-7 in human cancer cell lines suppressed cell viability and subsequently induced autophagy through inhibition of epidermal growth factor receptor (EGFR) expression. OBP-301 infection efficiently suppressed EGFR expression, which was significantly associated with miR-7 upregulation and cytopathic activity, in human cancer cell lines. Our results suggest that oncolytic adenovirus OBP-301 induces autophagic cell death through an E2F1-miR-7-EGFR pathway in human cancer cells, providing a novel insight into the molecular mechanism of an anticancer virotherapy. 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 2862. doi:10.1158/1538-7445.AM2011-2862
On the Edge of the Primeval Forest
Authors: K. Robertson
Journal: BMJ (2012)

When read with contemporary eyes, Albert Schweitzer’s book, subtitled “Experiences and Observations of a Doctor in Equatorial Africa,” is a disconcerting mix of startling racism and yet still pertinent commentary on African suffering. Schweitzer, a Christian missionary, physician, philosopher, and musician who qualified in medicine at the age of 38, funded his first trip to the Ogowe (or Ogooue) River with organ recitals and a book on Bach. The description of trying to land a piano (“built for the tropics”) and 70 cases by dugout canoe is both surreal and understated. His wife was a nurse and their approach to medicine was cutting edge scientific (they were intrigued by sleeping sickness trypanosomes in the blood), hygienic (Mrs Schweitzer washes a lot of bandages), …
Heterogeneity of Human Prekallikrein Deficiency (Fletcher Trait)
Authors: Hidehiko Saito, Lawrence T. Goodnough, Jeannette Soria, Claudine Soria, Justo Aznar, Francisco España
Journal: New England Journal of Medicine (1981)

We studied the plasma of 18 patients with a functional deficiency of plasma prekallikrein (Fletcher trait). Samples from 13 subjects contained less than 1 per cent of normal levels of prekallikrein antigen recognized by a specific antiserum (cross-reacting-material negative [CRM-]). In the five other subjects, however, nonfunctional material immunologically indistinguishable from normal prekallikrein was detected by radioimmunoassays at concentrations of 13 to 30 per cent (CRM+ variant). None of the plasma samples contained detectable circulating anticoagulants against prekallikrein. On immunodiffusion against antiserum to kallikrein, each of the five CRM+ samples formed a single precipitin line of complete identity with normal plasma or purified prekallikrein. On immunoelectrophoresis, the precipitin line had the same mobility as that for normal prekallikrein. These studies demonstrate the molecular heterogeneity of human prekallikrein deficiency and show that persons with the CRM+ variant have a nonfunctional form of prekallikrein in their plasma. (N Engl J Med. 1981; 305:910–4.)
ET-51 * COMBINED THERAPY WITH A NOVEL CXCR4 ANTAGONIST AND AN ANTI-VEGF ANTIBODY IMPAIRS THE GROWTH OF GLIOMAS
Authors: Y. Sarfraz, F. M. Alotaibi, V. Ortenzi, A. T. Tayyib, G. J. Douglas, E. Chevalier, B. Romagnoli, G. Tuffin, J.-P. Gagner, D. Zagzag
Journal: Neuro-Oncology (2014)

BACKGROUND: Expression of chemokine receptor CXCR4 and its ligand stromal cell-derived factor-1α (SDF-1α) is enhanced in glioblastoma, including at invasive edges, and associated with proliferation, invasion and angiogenesis (Zagzag, 2008; Ehtesham, 2013; Gagliardi, 2014). Using Protein Epitope Mimetics technology (Robinson, 2008), Polyphor Ltd. has developed selective, highly potent CXCR4 antagonists (De Marco, 2006), e.g., POL5551 (Ki: 0.5 nM). To address the problem of resistance to antiangiogenic therapy, we sought to determine whether POL5551 could inhibit the growth and/or invasion of gliomas in vivo. METHODS: Female adult C57BL/6 mice were implanted orthotopically with 1 x 105 CT-2A or GL261 glioma cells. On day 14, mice were randomized into 4 groups: 1) control, 2) POL5551 (5 mg/kg s.c.) twice daily, 3) anti-murine VEGF monoclonal antibody B20-4.1.1 (Genentech Inc.) (5 mg/kg i.p.) twice weekly (Bagri, 2010) and 4) combined POL5551 and B20-4.1.1. On day 28, brain tissues were processed, sections analyzed for tumor volume and invasion (H&E), vascular density (CD105) and apoptosis (caspase 3), and results compared (ANOVA). RESULTS: In CT-2A glioma-bearing mice, combined therapy significantly reduced tumor volume (17.3 ± 2.4 mm3, mean ± S.E.M.) compared with controls (57.2 ± 6.4, p < 0.01) and POL5551 (55.8 ± 11.2, p < 0.01), but not B20-4.1.1 (31.9 ± 8.7). The depth of tumor invasion was reduced by 47.5% (p < 0.07) with POL5551, but by only 10.3% with B20-4.1.1, and 24.4% with combined therapy. Comparable, but not statistically significant, results were obtained with GL261 gliomas. The concentration of POL5551 was higher in glioma tissues (87 ± 25.4 ng/g; 45.8 nM) than in brain adjacent to tumor (45 ± 4.8; 23.7) or normal brain (21 ± 1.5; 11.1) and sufficient to account for its biological effects. CONCLUSIONS: Although combined therapy did not reduce significantly glioma invasion, it did impair the growth of CT-2A and GL261 gliomas by 69.8% and 59.9%, respectively. Our results suggest the potential utility of POL5551 as adjunct therapy for glioblastoma.
PMO-184 Colonoscopic tattooing of colorectal neoplasia: a change in practice
Authors: A Brigic, J Clarke, A Haycock, S Thomas-Gibson
Journal: Gut (2012)

<h3>Introduction</h3> Quality Assurance Guidelines for colonoscopy in the Bowel Cancer Screening Programme recommend tattooing of all lesions that may require later surgical or endoscopic localisation, using local protocols as guidance.<sup>1</sup> The St. Mark9s Hospital colonoscopic tattooing protocol stated that all suspicious lesions should be tattooed, with the exception of those in the caecum and within 20 cm of the anal verge. Three tattoos should be placed (120° apart, close to the lesion) and distal to lesions proximal to the splenic flexure (SpFlx). Left sided lesions should have tattoos placed proximal to the lesion. Our aim was to audit compliance with the tattooing protocol in patients undergoing surgery for colorectal neoplasia. <h3>Methods</h3> We reviewed endoscopy reports of all patients who had surgery for colorectal neoplasia during a 12-month period. The report was deemed fully compliant if the following were clearly documented: location of the tattoos, correct location of the tattoos, the number of tattoos placed and a correct number of tattoos placed, hence, scoring 4/4. Non-compliance was defined if none of the parameters was mentioned and partial compliance was awarded to those scoring between one and three points. <h3>Results</h3> 155 patients were identified, of which 114 had reports available. The overall compliance with the protocol was observed in 71 cases (62%) whereas 19 cases (17%) were partially compliant and 24 cases (21%) were non-compliant. Rates for full, partial and incomplete compliance were better for patients diagnosed though the BCSP (71% 26% and 3% respectively) when compared to those diagnosed through non-screening (58%, 13% and 29% respectively). Incomplete documentation (22 cases) and inability to place tattoos proximal to obstructing lesions (19 cases) were the major causes of reduced compliance. <h3>Conclusion</h3> Educational intervention is necessary to address poor documentation. However, changes to our protocol are also required. We have therefore revised our protocol recommending that all tattoos should be placed distal to the lesion regardless of the anatomical position. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <i>Quality Assurance Guidelines for colonoscopy. NHS BCSP Publication No 6 February 2011</i>. http://www.cancerscreening.nhs.uk/bowel/publications/nhsbcsp06.pdf
CORONARY PLAQUE PROGRESSION OF NON-CULPRIT LESIONS AFTER CULPRIT PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH ADVANCED-STAGE CHRONIC KIDNEY DISEASE: INTEGRATED BACKSCATTER INTRAVASCULAR ULTRASOUND STUDY
Authors: Kuninobu Kashiyama, Shinjo Sonoda, Hironori Takami, Yoshitaka Muraoka, Yuki Tsuda, Masaru Araki, Yutaka Otsuji
Journal: Journal of the American College of Cardiology (2015)
Reaction of T-Lymphoid and B-Lymphoid Cell Lines With Rabbit Antisera Against These Lines 2
Authors: T. Tsubota, J. Minowada, D. Pressman
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Reaction of T-Lymphoid and B-Lymphoid Cell Lines With Rabbit Antisera Against These Lines Get access T. Tsubota, T. Tsubota Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Minowada, J. Minowada Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Pressman D. Pressman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 2, August 1977, Pages 399–404, https://doi.org/10.1093/jnci/59.2.399 Published: 01 August 1977 Article history Received: 28 October 1976 Accepted: 14 February 1977 Published: 01 August 1977
Top July Stories Are “5 A Day,” New Cancer Risks
Authors: John Bowersox
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Top July Stories Are “5 A Day,” New Cancer Risks Get access John Bowersox John Bowersox Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 15, 5 August 1992, Pages 1149–1151, https://doi.org/10.1093/jnci/84.15.1149 Published: 05 August 1992
Abstract 1854: Effects of supplemental antioxidant micronutrients on oxidative DNA damage marker in normal colorectal mucosa: A randomized clinical trial
Authors: Sindhu Lakkur, Thomas Ahearn, Roberd Bostick
Journal: Cancer Research (2011)

Abstract Background: Basic science and animal studies suggests that oxidative stress plays a role in colorectal oncogenesis. Smokers are reported to have increased oxidative DNA lesions in transformed colorectal epithelial cells and increased colorectal cancer risk; however, the majority of observational and clinical studies report weak or null associations between oxidative stress and risk of colorectal neoplasia. To address this we conducted, a pilot, randomized, double blinded, placebo controlled clinical trial to test the effects of an antioxidant micronutrient combination on a marker of oxidative DNA damage, 8-hydroxy-2’-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Methods: Forty-seven patients diagnosed with at least one pathology confirmed sporadic colorectal adenoma were given a daily antioxidant micronutrient combination (800mg dl-alpha-tocopherol acetate, 24 mg beta carotene, 1.0 g vitamin C, 200µg l-selenomethionine, 7.2 mg riboflavin, 80 mg niacin, 60 mg zinc, 5 mg manganese) or placebo for 4 months. A subset of patients (n=33) for whom tissue was available pre- and post supplementation was used in this analysis. 8-OH-dG was detected in biopsies of normal-appearing colorectal mucosa using standardized automated immunohistochemistry. Overall labeling and distribution of 8-OH-dG within the colon crypts were quantified by novel image analysis methods. Treatment effects were assessed using a MIXED effects model as implemented in SAS v9.2. Results: Relative to the placebo group, in the antioxidant group 8-OH-dG labeling decreased 13% (p=0.87) along the full length of crypts, 27% (p=0.49) in the upper third of crypts, 27 % (p=0.53) in the middle third of crypts, and 8% (p=0.92) in the bottom third of crypts. Among smokers (n=14), relative to the placebo group, in the antioxidant group 8-OH-dG labeling increased 6% (p=0.82) in the upper third of crypts, 28% (p=0.65) in the middle third of crypts, and 51% (p=0.50) in the bottom third of crypts. In non-smokers (n=18), relative to the placebo group, in the antioxidant group 8-OH-dG expression decreased 23% (p=0.55) in the upper third of crypts, 34% (p=0.44) in the middle third of crypts, and 24% (p=0.57) in the bottom third of crypts. Discussion: These preliminary findings, while not statistically significant 1) suggest that antioxidants may modulate oxidative DNA damage in the normal-appearing human colorectal epithelium – potentially modified by smoking status; 2) provide support for the use of 8-OH-dG as a potential treatable biomarker of risk for colorectal neoplasms; and 3) provide support for extending this investigation in a larger, more definitive trial. 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 1854. doi:10.1158/1538-7445.AM2011-1854
P17.84 * CANCER PROTEOMICS AND SYSTEMS BIOLOGY FOR PERSONALIZED MEDICINE
Authors: S. Souchelnytskyi, G. Stragliotto
Journal: Neuro-Oncology (2014)

Patients are different, so are tumors. Thus, it has to be the right treatment to the right person. People die of cancer because of late detection and/or lack of optimal treatment. Optimal treatment requires assessment of individual features of each cancer patient. There is a large gap in knowledge of how to make medicine personal. The goal is to understand molecular mechanisms, test drugs that are not primarily anti-cancer drugs as well as conventional alkylating agents and develop tools for individualized treatment of patients. Using proteomics platform that operates as the Open Access Center of Excellence (OACE), we could analyze comprehensive protein expression, protein-protein, protein-nucleic acid interaction, immunological analysis and activity-based proteome profiling (ex. kinases). We used both primary glioblastoma tissue from patient (3D) as well as growing circulating tumor cells from blood. We analyzed the sensitivity of several chemotherapy agents directly on tumors cells. We observed discrepancies in tumor cell death, as even if the MGMT was methylated, the response in vitro could be much lower than expected. Serial analyses of circulating tumors cells in blood can be a surrogate marker for tumor response, which correlates well to clinical evolution.
The Possible Diagnostic Role of Endoscopic Ultrasound in Patients with Unexplained Abdominal Pain
Authors: RA Zaydan
Journal: Endoscopy (2011)

Background and study aims: Although abdominal pain is a common presenting complaint, but evaluation of this complaint can be a challenge for even the most experienced clinicians. Endoscopic ultrasonography (EUS) now is a sensitive method to look for any pathology affects the upper gastrointestinal tract wall and adjacent organs which may be the etiology of the unexplained abdominal pain. This study evaluates the ability and effectiveness of the EUS in the detection of the etiology of unexplained abdominal pain.
Abstract 3806: Stimulation of anti-leukemia immune response by a rice protein prolamin
Authors: Hui-Fen Liao, Yu-Jen Chen, Yu-Yawn Chen
Journal: Cancer Research (2010)

Abstract Rice (Oryza sativa), an important cereal as a staple food worldwide, has been demonstrated that its water extracts benefit anti-leukaemia immunity. The present study isolated and characterized the active rice proteins and assessed the anti-leukemia response via in vitro and ex vivo experiments. Proteomic analysis identified various protein spots known with functions involving metabolism-related, transport, storage, antioxidation, development, and disease resistance proteins. Among these, storage proteins were the most abundant. To avoid masking the other relatively scanty rice storage proteins, albumin, globulin, glutelin and prolamin were separated and quantified. Prolamin-prepared conditioned medium of human mononuclear cells (MNC-CM) showed the greatest inhibition of human leukaemia U937 cell growth. Prolamin enhanced MNC to secrete tumor necrosis factor-α and prolamin-prepared MNC-CM induced U937 cells toward monocyte differentiation, not only by morphological observation, but also by NBT-reduction test. Neutralization of prolamin by polyclonal antibody attenuated its activity. Prolamin has greater activity than wheat gluten (glutenin and gliadin), which can cause celiac disease (CD). Additionally, rice proteins were undetectable by wheat gliadin-specific antibody, suggesting that rice may be an ideal candidate of food substitute in CD patients. In conclusion, rice prolamin is effective in activating human anti-leukaemia immunity and may not induce unwanted inflammatory diseases. 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 3806.
A Platelet-Inhibitor-Drug Trial in Coronary-Artery Bypass Operations
Authors: J. H. Chesebro, I. P. Clements, V. Fuster, L. R. Elveback, H. C. Smith, W. T. Bardsley, R. L. Frye, D. R. Holmes, R. E. Vlietstra, J. R. Pluth, R. B. Wallace, F. J. Puga, T. A. Orszulak, J. M. Piehler, H. V. Schaff, G. K. Danielson
Journal: New England Journal of Medicine (1982)

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in the placebo group. This benefit in graft patency persisted in each of over 50 sub-groups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation. (N Engl J Med. 1982;307:73–8.)
Case 41-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Stasha C. Gominak, Didier Cros
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 66-year-old woman was referred to the hospital because of progressive weakness of all extremities.The patient had been well until 19 years earlier, when she experienced the onset of a progressive left footdrop without pain, numbness, or paresthesias. A physician diagnosed intervertebral-disk disease, but no operation was advised. Twelve years before entry the patient began to have pains in the knees and hips, with muscular stiffness, and used analgesic medications almost daily. Five years before admission a marked waddle developed, and she began to walk with a cane; weakness developed in the arms. During the three . . .
Abstract 936: Ubiquitin-mediated interaction of p210 Bcr-Abl with β-catenin supports disease progression in a murine model for chronic myelogenous leukemia
Authors: Ru Chen, Gwen Mahon, Ilona Tala, Ian Whitehead
Journal: Cancer Research (2011)

Abstract Chronic myelogenous leukemia (CML) is a malignant hematopoietic stem cell disorder that is invariably associated with the expression of the p210 Bcr-Abl fusion protein. Although the deregulated, Abl-encoded tyrosine kinase activity is essential for disease progression, several studies have shown that Bcr encoded sequences are also necessary for p210 Bcr-Abl-mediated leukemogenesis. We have identified a non-classical ubiquitin binding domain (UBD) within the NH2-terminal Bcr sequences of p210 Bcr-Abl. Deletion of the UBD (p210 Bcr-Abl(ΔUBD)) does not impair the auto-or trans-kinase activity of p210 Bcr-Abl, nor does it impair the ability of p210 Bcr-Abl to interact with Grb2 and activate Erk1/2 signaling. Although β-catenin has been previously identified as a binding partner for Bcr and Bcr-Abl, p210 Bcr-Abl(ΔUBD) does not interact with β-catenin. Treatment with an E1 inhibitor impairs the interaction between β-catenin and p210 Bcr-Abl, suggesting that the interaction is ubiquitin-dependent. Over-expression of p210 Bcr-Abl, but not p210 Bcr-Abl(ΔUBD), leads to an accumulation of phosphorylated β-catenin, and at least two of its known transcriptional targets, cyclin D1 and c-Myc. Hyper-phosphorylation of β-catenin cannot be attributed to increased activity of GSK-3β or Pin-1. In a murine bone marrow transplantation model for CML, mice transplanted with hematopoietic cells that express p210 Bcr-Abl(ΔUBD) have significantly increased life spans compared to mice transplanted with p210 Bcr-Abl expressing cells. Delayed disease progression is associated with decreased levels of β-catenin, and reduced numbers of granulocyte macrophage progenitors (GMPs), in the bone marrow. Based on these observations we propose a model in which p210 Bcr-Abl may influence the Wnt signaling pathway, and leukemic expansion, by binding ubiquitinated β-catenin, and stabilizing it against degradation. Importantly, this activity is contained within Bcr sequences, and is independent of tyrosine kinase activity. 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 936. doi:10.1158/1538-7445.AM2011-936
CLINICAL OUTCOMES AFTER BARE-METAL STENTS DEPLOYMENT IN LARGE CORONARY ARTERIES IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION
Authors: John K. French, Ibrahim Shugman, Leia Hee, Sidney Lo, Phong Nguyen, Rohan Rajaratnam, Christian Mussap, Liza Thomas, Dominic Leung, Andrew P. Hopkins, Craig P. Juergens
Journal: Journal of the American College of Cardiology (2012)