tbuckley/cabot-search huggingface dataset:
TCT-724 Preprocedural But Not The Periprocedural High-sensitive Troponin T (hsTNT) Levels Predict Outcome In Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)
Authors: Wiebke M. Köhler, Sandra Freitag-Wolf, Doreen Brehm, Rainer Petzina, Georg Lutter, Norbert Frey, Derk Frank
Journal: Journal of the American College of Cardiology (2014)
Resection of Acute Ventricular Aneurysm and Ruptured Interventricular Septum after Myocardial Infarction
Authors: Willard M. Daggett, Lawrence R. Burwell, Dexter W. Lawson, W. Gerald Austen
Journal: New England Journal of Medicine (1970)

AMONG the anatomic derangements that follow myocardial infarction are perforation of the interventricular septum, infarction or rupture of papillary muscle and the development of ventricular aneurysm. Although there have been numerous reports of successful repair of these defects several months after the acute infarction, only a few reports have appeared describing successful early or emergency surgical repair of complications of myocardial infarction.1 2 3 The present report describes successful resection of an acute infarction of both the ventricular wall and the interventricular septum.Case ReportA 69-year-old woman, acutely ill and sweating, was admitted to the hospital after 5 hours of crushing . . .
Abstract 787: Tumor suppressor p53 inhibits expression of the pro-metastasis protein Toca-1.
Authors: Harish Chander, Colin D. Brien, Peter Truesdell, Doris Germain, Andrew W. B. Craig
Journal: Cancer Research (2013)

Abstract Transducer of Cdc42-dependent actin assembly-1 (Toca-1) is an adaptor protein that recruits key actin regulatory proteins to invadopodia in metastatic breast cancer cells. We recently showed that stable silencing of Toca-1 led to reduced invadopodia formation, cell invasion and tumor metastasis in an orthotopic xenograft model in mice. These results raise the possibility that Toca-1 upregulation may occur during tumor progression to metastatic disease. Here we show that Toca-1 expression is higher in triple negative breast cancers (HER2/ER/PR) compared to other subtypes. Since triple negative breast cancers frequently harbor mutations in the tumor suppressor p53, we tested whether p53 regulates Toca-1 expression. In wild-type (WT) p53-expressing normal breast epithelial and breast cancer cells, stabilization of WT p53 by inducing DNA damage, or treating cells with Mdm2 inhibitor Nutlin-3, led to dose-dependent reductions in Toca-1 mRNA and protein expression. Likewise, ectopic expression of WT p53 in p53-null HCC1806 cells also led to repression of Toca-1 levels. To test if this was a direct effect of p53 on the Toca-1 gene, chromatin immunoprecipitation (ChIP) studies were performed. Indeed, the proximal promoter region and intron 2 of the Toca-1 gene (which contained a predicted p53 binding site) were detected in p53 ChIP assays in WT p53-expressing cells, but not mutant p53 expressing breast cancer cells. Together, these results identify a novel pathway to inhibit Toca-1 expression in cells with WT p53, and imply that the loss of p53 in highly metastatic breast cancer subtypes may lead to elevated Toca-1 expression and progression to metastatic disease. Citation Format: Harish Chander, Colin D. Brien, Peter Truesdell, Doris Germain, Andrew W. B. Craig. Tumor suppressor p53 inhibits expression of the pro-metastasis protein Toca-1. [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 787. doi:10.1158/1538-7445.AM2013-787
ABC of breast diseases: Role of Systemic Treatment for Primary Operable Breast Cancer
Authors: M A Richards, I E Smith, J M Dixon
Journal: BMJ (1994)

Over half of women with operable breast cancer who receive locoregional treatment No of involved nodes: alone (surgery with or without radiotherapy) Tumou sze ad g will die from metastatic disease, indicating lIcm that for most women the cancer has already 0 spread by the time of presentation.The major p < o.oo1 >Icm,grade or l >Icm, grade III risk factors for development of metastases are axillary lymph nodes being involved, an 1-3 adverse histological grade (indicating an 4-9undifferentiated cancer), and large tumour size.Combinations of these factors can be >,10 P ~= 0.0056 used to define groups with widely different risks of relapse: from less than 10% to more than 90% remaining free of disease after five years.The only way to improve the chance of survival for many of these women is to give Survival without relapse of patients with operable breast cancer (data from Guy's them effective systemic treatment. Hospital, London).*Absolute benefit may be about half as great for stage cancer.tFor example, >6 months of cyclophosphamide, methotrexate, and fluorouracil.*Estimates unreliable because of small amount of data. Side effects of drugs used for adjuvant treatmentChemotherapy * Fatigue and lethargy * Risk of infection * Alopecia (temporary) * Oral mucositis * Nausea and vomiting * Diarrhoea * Induction of menopause 0 Weight gain * Specific side effects of certain drugs Oophorectomy * Induction of menopause * Hot flushes * Vaginal dryness * Osteoporosis Gonadotrophin releasing hormone analogues * As for oophorectomy * Pain and bruising at injection site Tamoxifen * Hot flushes * Altered libido * Gastrointestinal upset * Vaginal dryness * Menstrual disturbance * Weight gain * Visual disturbances-rare (stop drug if reported)
Abstract LB-359: Plasma microRNAs as novel biomarkers for lung cancer
Authors: Dali Zheng, Michael X. Wang
Journal: Cancer Research (2010)

Abstract Objective: Lung cancer is the leading cause of cancer-related deaths in both men and women. Since there is no validated population-based screening procedure, most patients with lung cancer are diagnosed at advanced stages with an overall five-year survival rate of only 15%. Therefore, diagnosis of lung cancer at an early stage is important for improving the outcome of patients. MicroRNAs (miRNAs), a family of 19- to 25-nucleotide and noncoding small RNAs that primarily function as gene regulators at post-transcriptional level, are frequently dysregulated in cancer. Recent studies demonstrate that the miRNAs in blood are present in notably stabile form and are readily detectible by various sensitive methods. This new finding has raised a concept that circulating miRNAs could be novel non-invasive biomarkers for cancer detection. The objective of this study is to investigate the potential of circulating microRNAs for lung cancer detection. Methods: First, we searched the miRNA microarray data of lung cancer from published literature, and selected 15 of miRNAs (miR-17, 21, 24, 106a, 125b, 128, 155, 182, 183, 197, 199b, 203, 205, 210 and 221) that were most frequently up-regulated in lung cancer tissues. Total RNA including miRNAs were isolated with mirVana PARIS kit (Ambion, TX), then polyadenylated and reverse-transcribed with a poly(T) adapter into cDNAs for real-time PCR using the miRNA-specific forward primer and the sequence complementary to the poly(T) adapter as the reverse primer. The levels of miRNAs were determined in 28 plasma samples from lung cancer patients and 16 of controls. Results: We found that the levels of miR-155, miR-182 and miR-197 in plasma of lung cancer patients were significantly elevated compared with controls. MiR-155 yielded an AUC (the areas under the ROC curve) of 0.8739 (95% CI:0.7489 to 0.9989, P&amp;lt;0.001), miR-182 yielded an AUC of 0.8426 (95% CI:0.7239 to 0.9614, P&amp;lt;0.001) and miR-197 yielded an AUC of 0.8037 (95% CI:0.6705 to 0.9369, P&amp;lt;0.001) in discriminating lung cancer from controls. Conclusions: MiR-155, miR-182 and miR-197 are significantly elevated in patient plasma with lung cancer and can be a potential non-invasive molecular biomarker for lung cancer screening and clinical follow-up. 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 LB-359.
Active Immunization against Scarlet Fever
Authors: Manuel M. Glazier
Journal: New England Journal of Medicine (1945)

THERE are a substantial number of physicians who are opposed to active immunization against scarlet fever, claiming that the accompanying reactions are unusually severe. The presence of this opposition, despite the fact that such immunization has been shown to be effective,1 2 3 is thought provoking, and for this reason, a report is presented of the reactions in 377 private patients actively immunized against scarlet fever during the last thirteen years.The purpose of this paper is to describe a method of active immunization against scarlet fever through use of graduated doses of scarlet-fever streptococcus toxin that was found effective both in . . .
Intimal-Medial Thickness of the Carotid Artery in NIDDM Patients
Authors: Gábor Winkler, Ferenc Salamon, Marietta Porochnavec, Diana Solymosi, Jolán Demeter, Kornél Simon, Dániel Salamon, Istváan Karádi, Károly Cseh, Lászlo Romics
Journal: Diabetes Care (1997)
Ischemic Retinopathy Caused by Severe Megaloblastic Anemia
Authors: K Li, G McKay
Journal: New England Journal of Medicine (2000)

Figure 1. A 36-year-old woman who had been a vegan for many years presented with a one-week history of decreased visual acuity. She had had megaloblastic anemia six years earlier (hemoglobin, 7.5 g per deciliter) that was found to be due to folic acid deficiency. At that time, her serum level of vitamin B12 was normal, as were the results of a Schilling test. There was no evidence of malabsorption, and an x-ray study of her small bowel was normal. She was briefly treated with oral folic acid but then did not return for follow-up appointments. When she presented . . .
IS LESS MORE? BENEFITS OF A NEW SINGLE-CHAMBER ICD WITH ATRIAL SENSING COMPARED WITH DUAL-CHAMBER ICD
Authors: Obiora Maludum, Percy Balderia, Yolanda Nixon, Bernadette Sheeron, Jessica Smukler, Kamal Joshi, Allan Greenspan, Sumeet Mainigi
Journal: Journal of the American College of Cardiology (2015)
Reserpine in Thyrotoxic Crisis
Authors: Pauline T. Dillon, John Babe, C. R. Meloni, John I. Canary
Journal: New England Journal of Medicine (1970)

In view of the beneficial effects of reserpine and beta-adrenergic blocking agents in thyrotoxicosis, we evaluated reserpine alone in seven thyrotoxic patients with eight episodes of thyroid storm. All had hyperthermia, exaggerated thyrotoxic signs and symptoms. All survived. Initially, 1 to 5 mg of reserpine was given intramuscularly, and 0.07 to 0.3 mg per kilogram of body weight was administered in the first 24 hours. Hyperthermia, hyperhidrosis, tachycardia and psychologic aberrations improved within four to eight hours. More rapid responses were seen with higher initial doses. In two patients mild diarrhea occurred; in one of these a transient cutaneous blush and increased tremor was noted on the first day. Hypotension did not occur, and cardiac failure when present improved. Reserpine in large parenteral doses appears to provide effective therapy for thyrotoxic crisis. It may be used alone or in conjunction with the usual modes of treatment.
Risk of Leukemia after Platinum-Based Chemotherapy for Ovarian Cancer
Authors: Lois B. Travis, Eric J. Holowaty, Kjell Bergfeldt, Charles F. Lynch, Betsy A. Kohler, Tom Wiklund, Rochelle E. Curtis, Per Hall, Michael Andersson, Eero Pukkala, Jeremy Sturgeon, Hans Storm, E. Aileen Clarke, John D. Boice, Mary Gospodarowicz, Marilyn Stovall
Journal: New England Journal of Medicine (1999)

Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment.
PillCam Colon and ulcerative colitis: what do physicians need to know?
Authors: G. Manes, S. Ardizzone, A. Cassinotti
Journal: Endoscopy (2013)

We read with interest the paper from Sung et al., reporting their first experience with colon capsule endoscopy (CCE) in the assessment of ulcerative colitis [1]. We agree with their conclusion that CCE is a promising tool, but we think that the results of the study are not generalizable and do not reflect possible clinical use of CCE. Our impression arises from our smaller experience with 20 patients with ulcerative colitis (severe acute relapse, 4; mild/moderate recurrence, 11; and clinical remission, 5) who underwent first-generation CCE and colonoscopy on the same day, similarly to the patients in the study of Sung et al. The colon was cleaned as described by Eliakim et al. [2], and mucosal changes were assessed using the Baron score.
Writing New Rules for Insurers — Progress on the Medical Loss Ratio
Authors: Timothy Stoltzfus Jost
Journal: New England Journal of Medicine (2010)

Few undertakings in the short history of the implementation of health care reform have been as difficult or contentious as the drafting of regulations to define the statute's “medical loss ratio” requirement. Beginning in 2011, health insurers must report annually the percentage of their premium revenue (excluding expenditures for taxes and regulatory fees) that they spend on “reimbursement for clinical services” and on “activities that improve health care quality.” This is their medical loss ratio. If the medical loss ratio of an insurer in the individual or small-group market falls below 80% (or, for large-group insurers, 85%), the insurer must . . .
Abstract 4254: Human neuroendocrine Bon 1 cells as a three-dimensional model for the study of human neuroendocrine tumor therapy
Authors: Eugenia Y. Xu, Chung Wong, Arnold J. Levine, Evan Vosburgh
Journal: Cancer Research (2012)

Abstract Pancreatic neuroendocrine tumors are rare tumors, with an incidence of one to two per 100000 individuals per year, and they account for 1-2% of all pancreatic neoplasms. Currently, much needed is to develop the therapeutical drugs for patients with pancreatic neuroendocrine tumors. Human pancreatic neuroendocrine BON 1 cell line is widely used for testing the therapeutic drugs in vitro. Here, we develop an alternative research model that better mimics the in vivo tumor tissue organization and microenvironments. This method produces in vitro three-dimensional (3D) tumor spheroids from human pancreatic BON1 cells. The 3D tumor spheroids generated in vitro exhibit the characteristics of avascular tumors. Structurally and genetically the 3D spheroids show similarity to the xenograft BON1 tumor and are more tumorigenic than 2D monolayer BON1 cells. We also present how to use these 3D spheroids to screen the therapeutic drugs. This method will help us establish human neuroendocrine tumor spheroids for cancer therapy. 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 4254. doi:1538-7445.AM2012-4254
Abstract 3404: Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma.
Authors: Maria R. Girotti, Malin Pedersen, Berta Sanchez-Laorden, Amaya Viros, Samra Turajlic, Dan Niculescu-Duvaz, Alfonso Zambon, John Sinclair, Andrew Hayes, Martin Gore, Caroline Springer, James Larkin, Claus Jorgensen, Richard Marais
Journal: Cancer Research (2013)

Abstract We generated melanoma cell lines resistant to BRAF inhibitors and show that the EGF receptor (EGFR)-SRC family kinase (SFK)-STAT3 signaling pathway was upregulated in these cells. In addition to driving proliferation of resistant cells, this pathway also stimulated invasion and metastasis. EGFR inhibitors cooperated with BRAF inhibitors to block the growth of the resistant cells in vitro and in vivo, and monotherapy with the broad specificity tyrosine kinase inhibitor dasatinib blocked growth and metastasis in vivo. We analyzed a tumor from a BRAF mutant patient with intrinsic resistance to vemurafenib. Vemurafenib treatment induced SFK activation in this tumor and we show that dasatinib blocked its growth and metastasis in immunocompromised mice. Our data shows that BRAF inhibitor-mediated activation of EFGR/SFK/STAT3 signaling can mediate resistance in BRAF mutant melanoma patients. We describe two treatments that appear to overcome this resistance and could deliver therapeutic efficacy in drug-resistant BRAF mutant melanoma patients. Citation Format: Maria R. Girotti, Malin Pedersen, Berta Sanchez-Laorden, Amaya Viros, Samra Turajlic, Dan Niculescu-Duvaz, Alfonso Zambon, John Sinclair, Andrew Hayes, Martin Gore, Caroline Springer, James Larkin, Claus Jorgensen, Richard Marais. Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma. [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 3404. doi:10.1158/1538-7445.AM2013-3404
Abstract PD07-05: In Situ Immune Response after Neoadjuvant Chemotherapy for Breast Cancer Predicts Survival
Authors: S Ladoire, B Coudert, P Fumoleau, L Arnould, F. Ghiringhelli
Journal: Cancer Research (2010)

Abstract Purpose: Accumulating preclinical evidence suggest that anticancer immune responses contribute to the success of chemotherapy. However, the prognostic value of tumor infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. Patients and Methods: In a series of 111 consecutive HER2 and a series of 51 non HER2 overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumor infiltration by Foxp3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modeling were used to assess relapse-free survival (RFS) and overall survival (OS). A prognostic scoring system using American Joint Committee on Cancer (AJCC) pathologic staging and immunological markers was created. Results: Association of high CD8 and low Foxp3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p=0.02) and OS (p=0.002), and outperformed classical prognostic factors in multivariate analysis. A combined score associating CD8/Foxp3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with favorable prognosis in an independent cohort of HER2 negative breast cancer patients. Conclusion: Immunological CD8 and Foxp3 cell infiltrate after treatment is a novel independent prognostic factor of survival in breast cancer patients treated with neoadjuvant chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-05.
THU0465 Severe Fibrodysplasia Ossificans Progressiva in a 3-Year-Old Girl with Atypical Acvr1 Mutation (G356D)
Authors: J. Postępski, A. Poluha, E. Olesińska, P. Sikora
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibrodysplasia ossificans progressiva (FOP, MIM #135100), is an extremely rare genetic disorder characterized by progressive formation of extraskeletal bone (heterotopic endochondral ossification, HEO) and specific congenital malformation of the great toes. A heterozygous activating mutations in the gene encoding ACVR1 (a bone morhogenic protein type I receptor) are responsible for the symptoms of the disease. <h3>Objectives</h3> We present a 3-year-old girl with severe form of FOP and atypical <i>ACVR1</i> mutation (G356D). <h3>Results</h3> Our patient was born at term to healthy no consanguineous parents. There was no significant medical history in her family. On postpartum physical examination bilateral deformation of toes and thumbs were found. Middle phalanges of fingers II, IV at both hands were underdeveloped. There was structural heart malformation (ASD II, PDA). The first sign of soft tissue ossification was noted after routine vaccination in the first month of life. Initially the symptoms were misdiagnosed. In the following months, a number of extra-bone ossification lesions were developing at the neck, back, shoulders and forearms, most frequently after minor injuries. All of them were preceded by painful inflammatory soft tissues swellings, of which some regressed spontaneously. The clinical diagnosis of FOP has been established at the age of 15 months, confirmed by the presence of atypical heterozygous <i>ACVR1</i> mutation (1067G&gt;A; G356D) discovered by sequencing of ACVR1 gene. So far, G356D mutation has been reported in connection to a milder phenotype of FOP. However, in our patient, the course of the disease is severe, rapidly progressive, leading to significant disability. <h3>Conclusions</h3> Although extremely rare, FOP should always be considered in differential diagnosis of children presenting with heterotopic endochondral ossification, especially coexisting with congenital malformation of toes. In the present case we demonstrate the severe end of spectrum of classic clinical features of FOP in an individual with atypical <i>ACVR1</i> mutation (1067G&gt;A; G356D). <h3>References</h3> Kaplan FS, Chakkalakal SA, Shore EM. Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis. Dis Model Mech. 2012;5:756-62 Furuya H, Ikezoe K, Wang L, Ohyagi Y, Motomura K, Fujii N, Kira J, Fukumaki Y. A unique case of fibrodysplasia ossificans progressiva with an <i>ACVR1</i> mutation, G356D, other than the common mutation (R206H). Am J Med Genet A. 2008;146:459-63 Miao J, Zhang C, Wu S, Peng Z, Tania M. Genetic abnormalities in fibrodysplasia ossificans progressiva. Genes Genet Syst. 2012;87:213-9 Kaplan FS, Shore EM, Pignolo RJ et all. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP 2011;4:1-100 <h3>Disclosure of Interest</h3> None Declared