tbuckley/cabot-search huggingface dataset:
Abstract 1857: Src: A novel target for chemoprevention of early stage ER- breast cancer
Authors: Shalini Jain, Maitri Shah, Ping Li, Qingfei Wang, Siyuan Zhang
Journal: Cancer Research (2011)

Abstract Selective ER modulators (SERMs) have shown significant efficacy for the prevention of ER-positive breast cancer, however, SERMs are not effective for patients whose tumors do not express ER. Therefore, novel agents are needed for prevention and intervention of high risk ER-breast cancers. The c-Src plays a pivotal role in the progression of EGFR- and HER2-dependent ER negative breast cancer. Thus, targeting Src using agents with minimal toxicity or in combination with other novel agents may prevent/intervene progression of early stage ER- breast cancer. In this study we used Saracatinib (AztraZeneca), a Src inhibitor well-tolerated in phase II clinical trials. We examined the effect of Src inhibition using Saracatinib alone or with other agents for cancer prevention using human mammary epithelial pre-malignant cell lines (MECs) and MMTV-neu mouse model. The MCF10A MECs stably overexpressing ErbB2 (10A.ErbB2 cells) form irregular (grape-like) acini in 3D culture condition. Saracatinib treatment prevents the progression of abnormal 3D acini growth as well reverses the abnormal 3D acini growth of 10A.ErbB2 cells to normal phenotype. Our reverse phase protein array data showed that Saracatinib induces the expression of cell cycle inhibitors and apoptosis related molecules, e.g. P27kip1, RAR beta, and PDCD4. Our 3D acini confocal microscopy experiment showed that it induces luminal apoptosis and suppresses cell proliferation in 10A.ErbB2 cells as detected by activated caspase-3 and ki-67 staining respectively. Next, we used MMTV-neu mouse model which develop ER negative lesions at early stage, to examine correlation between Src activation and ER negative mammary cancer progression. MMTV-neu mice mammary lesions exhibited super-activated Src which were negatively associated with estrogen receptor (ER) expression. Our preliminary data showed that Saracatinib-containing regimen inhibited MMTV-neu mice mammary lesions. Our study demonstrated that targeting Src by Saracatinib may be effective for the chemoprevention of early stage ER negative breast cancer. 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 1857. doi:10.1158/1538-7445.AM2011-1857
Lower-Extremity Function in Persons over the Age of 70 Years as a Predictor of Subsequent Disability
Authors: Jack M. Guralnik, Luigi Ferrucci, Eleanor M. Simonsick, Marcel E. Salive, Robert B. Wallace
Journal: New England Journal of Medicine (1995)

Functional assessment is an important part of the evaluation of elderly persons. We conducted this study to determine whether objective measures of physical function can predict subsequent disability in older persons.
Abstract 4969: Impact of proteasome inhibition of caspase-8 regulation in cancer
Authors: Michael Fiandalo, Steven Schwarze, Natasha Kyprianou
Journal: Cancer Research (2012)

Abstract Dissection of the extrinsic and intrinsic pathways of apoptosis has lead to the development of new anti-cancer therapeutic strategies. Strategies involve combination of a chemotherapeutic agent with a death inducing ligand, such as TNF-alpha Related Apoptosis Inducing Ligand (TRAIL) to induce apoptosis in cancer cells that are resistant to apoptosis. We recently demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer to TRAIL mediated apoptosis using both in-vitro and in-vivo models, by stabilizing the active p18 subunit of initiator caspase-8. Based on this data indicating a potential relationship between caspase-8 and the proteasome, we hypothesize that caspase-8 ubiquitination and targeting to the 26S proteasome regulates the extrinsic pathway of cancer cell apoptosis. This study pursues the impact of proteasome inhibition on caspase-8 stability, trafficking and activity following death receptor activation. The contribution of caspase-8 polyubiquitination in regulating the extrinsic pathway of apoptosis is determined, using subcellular fractionation, caspase-8 and polyubiquitin immunoprecipitation (IP), and fluorescent microscopy techniques in diverse experimental cell models. The cell lines analyzed include the TRAIL resistant LNCaP prostate cancer cell line and caspase-8 deficient neuroblastoma (NB7) cell line, engineered to re-express and test the wild-type and non-cleavable mutant forms of caspase-8. Our findings indicate that the non-cleavable forms of caspase-8 are capable of inducing apoptosis comparably to wild-type caspase-8 upon treatment with proteasome inhibitor and TRAIL. Moreover we provide evidence that caspase-8 polyubiquitination occurs following caspase-8 processing into its active subunits, processed caspase-8 accumulates at the DISC, and ultimately cycles into the cytosol for proteasomal degradation. This study identifies caspase-8 processing as a significant regulatory mechanism in apoptosis outcomes in cancer cells, but not required for caspase-8 activation. Together these data provide a better understanding of caspase-8 regulation that can be used as a platform for identifying new molecular targets such as E3 ligases responsible for caspase-8 regulation. Further defining caspase-8 regulation can lead to strategies that enhance efficacy of current therapies or lead to development of new more specific caspase-8 driven anti-cancer approaches. Funding provided by DOD GRANT USAMRMC PC073314 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 4969. doi:1538-7445.AM2012-4969
Risk-Based Management of Prostate Cancer
Authors: Anthony V. D'Amico
Journal: New England Journal of Medicine (2011)

Randomized trials (EORTC 228631; SPCG-72; and TROG 96013) (Table 1) have established external-beam radiation therapy plus hormonal therapy (combined therapy) as a standard of care for men with adenocarcinoma of the prostate that is locally advanced (stage T3 or T4) or high-risk localized disease (defined as one or more of the following: a prostate-specific antigen [PSA] level >20 ng per milliliter, a Gleason score [the sum of the two most common histologic patterns or grades in a prostate tumor, each of which is graded on a scale of 1 to 5, with 5 indicating the most aggressive . . .
Sympathetic-Nerve Activity during Sleep in Normal Subjects
Authors: Virend K. Somers, Mark E. Dyken, Allyn L. Mark, Francois M. Abboud
Journal: New England Journal of Medicine (1993)

The early hours of the morning after awakening are associated with an increased frequency of events such as myocardial infarction and ischemic stroke. The triggering mechanisms for these events are not clear. We investigated whether autonomic changes occurring during sleep, particularly rapid-eye-movement (REM) sleep, contribute to the initiation of such events.
von Hippel-Lindau and the Genetics of Astrocytoma
Authors: J. L. Rubenstein, H. Yaari, S. Calif
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article von Hippel-Lindau and the Genetics of Astrocytoma Get access James L. Rubenstein, James L. Rubenstein Department of Medicine, Stanford University School of MedicineStanford, Calif Correspondence to : James L. Rubenstein, M.D., Ph.D, Department of Medicine, Stanford University School of Medicine, S102C, Stanford, CA 94305. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hana Yaari, Hana Yaari Cornell University Medical College New YorkN. Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stanford Calif Stanford Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Pages 142–143, https://doi.org/10.1093/jnci/86.2.142 Published: 19 January 1994 Article history Received: 13 September 1993 Revision received: 14 October 1993 Accepted: 25 October 1993 Published: 19 January 1994
Abstract B63: Identification of small molecules that selectively target glioma stemlike cells
Authors: S. Kyun Lim, Shuguang Wei, Darren Samples, Yanjiao Li, Woosung Cho, Renee McKay, Noelle S. Williams, Bruce A. Posner, Luis F. Parada
Journal: Cancer Research (2011)

Abstract Gliomas are the most frequently occurring primary malignancies in the central nervous system, with glioblastoma multiforme (GBM) the most common and most aggressive of these tumors. GBM is virtually incurable because, following the standard treatment of care—surgical resection, radiation, and chemotherapy—the tumors eventually recur. Recent studies including our own indicate a crucial role for a specific subset of tumor cells (cancer stem cells) in tumor development and recurrence. We have generated fully penetrant, tumor-suppressor-based somatic mouse models of glioma, with gene mutations frequently found in human glioma (p53, NF1, Pten; termed Mut6 tumors). These tumor models develop GBM that histopathologically and molecularly mimics the human disease. Transcriptional profiling of these tumors revealed that they are most similar to human GBM. Using the pooled Mut6 stem-like cancer cells we performed a high-throughput screen designed to identify small molecules that inhibit the growth of these cells, as measured by a luminescence ATP assay. We performed a 200,000 compound library screen, initially identifying 4,480 compounds that were then retested in increasingly stringent assays such that we now have approximately 70 unique compounds that adversely affect glioma stem cell growth. These compound hits were found to have EC50s in the nanomolar range and to act with considerable specificity, affecting the mutant stem cells at concentrations that do not affect cultured astrocytes or mouse embryonic fibroblasts. Among these, we tested 46 compounds in metabolic stability tests and found 17 compounds with excellent stablilty profiles. We believe these compounds present promising lead compounds for drug development as well as for uncovering critical pathways in glioma tumor development and self renewal. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B63.
‘Straight Line’ Sign of Diffuse Peritoneal Carcinomatosis on Sagittal FDG Positron Emission Tomographic Images
Authors: EUGENE C. LIN
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology, University of Colorado Health Sciences Center, Denver, Colorado Received for publication October 22, 2001. Revision accepted February 26, 2002. Reprint requests: Eugene C. Lin, Virginia Mason Medical Center, Mailstop C5-XR, 1100 Nineth Avenue, P.O. Box 900, Seattle, Washington 98111. E-mail: [email protected]
Inequalities cause reproductive deaths
Authors: L. Dillner
Journal: BMJ (1995)

A US organization, Population Action International, is reported in this article to have released findings on the health risks for women in 118 countries. Countries are ranked on 10 indicators, including such indicators as the number of births to women aged under 19 years, the availability of legal abortion, maternal mortality, and level of prenatal care. Italy, Denmark, Norway, and Sweden are identified as countries with low reproductive risk for women. The worst ranked countries are identified as Zaire, Angola, and Somalia. 21 countries were placed in the high risk group, of which only two, Haiti and Afghanistan, are not located in Africa. Editorial comment in the report is described in this article as reflecting the position that countries fail in investing in women's health, with devastating consequences. Some poor countries, such as Cuba, Tunisia, and Costa Rica, are cited for their investments in health care and family planning. The report is described as asserting that low status also prevents women from maintaining good health. Both access to reproductive health services and changing social norms supporting traditional roles in early and frequent childbearing are important to women's improved health status. It is also important for women to have educational and economic opportunities. Population Action International is seeking greater foreign aid contributions for family planning services in developing countries, emergency care in childbirth, health education, AIDS education, and access to safe abortion services.
THE ROLE OF ADAPTIVE SERVO-VENTILATION IN REDUCING REHOSPITALIZATION FOR ELDERLY PATIENTS WITH HEART FAILURE
Authors: Kayo Hara, Hideki Okayama, Go Hiasa, Go Kawamura, Tatsuya Shigematsu, Tatsunori Takahashi, Masaki Kinoshita, Toru Miyoshi, Akinori Higaki, Yoshitaka Kawata, Tadakatsu Yamada, Yukio Kazatani
Journal: Journal of the American College of Cardiology (2015)
AORTIX™, A NOVEL CATHETER-BASED INTRA-VASCULAR ASSIST DEVICE, PROVIDES CARDIO-RENAL SUPPORT WHILE IMPROVING VENTRICULO-ARTERIAL COUPLING AND MYOCARDIAL DEMAND IN SHEEP WITH INDUCED CHRONIC ISCHEMIC HEART FAILURE
Authors: Carlos del Rio, William Clifton, Jace Heuring, Benjamin Hertzog, Yukie Ueyama, Bradley Youngblood, Patrick I. McConnell
Journal: Journal of the American College of Cardiology (2015)
Demonstration of Collateral Arterial Flow after Interruption of Hepatic Arteries in Man
Authors: E. Truman Mays, Chalmer S. Wheeler
Journal: New England Journal of Medicine (1974)

After delineating hepatic arterial flow in 20 patients, we dispute the concept that hepatic arteries are end arteries. Selective arteriography shows retrohepatic arterial flow 10 hours after interruption of hepatic arteries. When either the right or the left hepatic artery is interrupted adjacent to the liver, intrahepatic translobar vessels establish flow in the ligated system. Such intrahepatic vessels between the right and left rami cannot be portrayed by cadaver liver perfusions, nor are they apparent on arteriograms of normal subjects. If the common hepatic artery is interrupted, revascularization occurs through inferior phrenic, pancreaticoduodenal and intercalary de novo arteries. Hepatic necrosis after hepatic-artery ligation in man is rare if portal-vein flow and oxygenation are optimum until arterial flow is reconstituted. Complete dearterialization of the human liver cannot be accomplished by simple ligature or excision. (N Engl J Med 290:993–996, 1974)
Traitement des fistules digestives avec le système „Over-the-scope„ clip
Authors: P Mercky, V Vitton, JC Grimaud, M Barthet
Journal: Endoscopy (2011)

Introduction: Le traitement des fistules du tractus digestif est difficile avec des récidives fréquentes. Le nouveau système de clips „over-the-scope„ (OTSC®, Ovesco Endoscopy GmbH, Tuebingen, Allemagne) par sa taille, sa force occlusive et la distance entre les „bras„ du clip, pourrait être une alternative prometteuse pour le traitement des fistules digestives.
Study on contrast enhanced EUS in pancreatic disease
Authors: Zhu Qi, Gong Ting-ting, Xiong Hui-fang, Zhang Yi, Sun Yun-wei, Tan Ji-hong, Xia Lu
Journal: Endoscopy (2011)

Background: The differenzial diagnosis of pancreatic disease is still crucial. Invasive measures which can obtain tissue samples have high specificity. However, contrast-enhanced endoscopic ultrasonography (CE-EUS) may offer a non-invasive option and better visualization.
Screening for Inborn Errors of Metabolism Associated with Mental Deficiency or Neurologic Disorders or Both
Authors: Adhemar W. Renuart
Journal: New England Journal of Medicine (1966)

THE term "inborn error of metabolism" was first coined by Garrod1 in 1908, when he described alkaptonuria, albinism, pentosuria and cystinuria as a group of diseases that tended to occur in families, especially when there was consanguinity. He postulated that each disease was due to a block in the normal metabolic pathway. The concept of "one gene-one enzyme" was formulated by Beadle2 in 1945 as a result of his work and studies on eye color in the fruit fly, drosophila. And, finally, the "one gene-one enzyme-one disease" sequence was demonstrated by Cori and Cori3 in 1952 in their work on . . .
Pharmaceutical Industry Buys In to Managed Care
Authors: K. Nagy
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Pharmaceutical Industry Buys In to Managed Care Get access Kate Nagy Kate Nagy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 17, 6 September 1995, Pages 1278–1279, https://doi.org/10.1093/jnci/87.17.1278 Published: 06 September 1995
Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders
Authors: Franklin H. Epstein, Stuart A. Lipton, Paul A. Rosenberg
Journal: New England Journal of Medicine (1994)

In many neurologic disorders, injury to neurons may be caused at least in part by overstimulation of receptors for excitatory amino acids, including glutamate and aspartate. These neurologic conditions range from acute insults such as stroke, hypoglycemia, trauma, and epilepsy (Table 1) to chronic neurodegenerative states such as Huntington's disease, the acquired immunodeficiency syndrome (AIDS) dementia complex, amyotrophic lateral sclerosis, and perhaps Alzheimer's disease (Table 2)13.Glutamate is the principal excitatory neurotransmitter in the brain, and its interactions with specific membrane receptors are responsible for many neurologic functions, including cognition, memory, movement, and sensation4. In addition, excitatory . . .
OT-06 * MULTICENTRIC PRIMARY CENTRAL NERVOUS SYSTEM DIFFUSE LARGE B CELL LYMPHOMA IN AN INMUNOCOMPETENT ADOLESCENT, CASE REPORT
Authors: J. Leon, R. Cardenas, M. Zapata, L. Velasco
Journal: Neuro-Oncology (2015)

BACKGROUND: Primary central nervous system lymphoma (PCNSL) accounts for 4 to 7% of all primary intracranial neoplasms and 1 to 2% of all lymphomas. PCNSL incidence has increased tenfold over the last three decades in both immunocompetent and immunocompromised individuals. CASE REPORT: We present the case of a female adolescent with no risk factors for immunosuppression. Her immunological profile was normal. Her main symptom was headache two years before being diagnosed with a primary central nervous system diffuse large b cell lymphoma. Left ptosis, facial paralysis, disarthria and diplopia appeared one year later. She developed paresthesias in both hands with loss of strength. One month before she had seizures. In the magnetic resonance a multilobulated heterogeneous mass in left ventricule was found with high contrast enhancement. In spinal cord at C1-C2, an intramedular heterogeneous lesion was also observed. Stereotactic biopsy was done reporting CD20+ primary central nervous system diffuse large b cell lymphoma with reactive gliosis. Cerebrospinal fluid was negative. No viral association was detected. DISCUSSION: PCNSL are a rare malignant neoplasm in pediatric age, and more common in male. Worldwide, near fourteen cases are diagnosed each year. Most of these cases appear in immunocompromised patients. This is a special case because of the association of lymphoma in an immunocompetent girl. Clinical features differs in the evolution time which is longer than expected for a lymphoma. Radiological imaging suggests a multicentric presentation or a previous non-diagnosed disease. These cases suggests that lymphoma have a different clinical, radiological and histological presentation when the localization is in central nervous system. Malignant tumors have a non-predictable evolution in this tissue. Do we have to treat it in the same way?
Pulmonary Alveolar Microlithiasis, or Calcinosis of the Lungs
Authors: Theodore L. Badger, Leonard Gottlieb, Edward A. Gaensler
Journal: New England Journal of Medicine (1955)

PULMONARY alveolar microlithiasis is a rare and extraordinary disease in which microscopic stones are found within the pulmonary alveoli. The lungs, which are heavy and stony hard, cut with the greatest of difficulty. As far as can be determined this disease was first described by Friedreich1 in 1856; its present name was originally used by Puhr2 in 1933.The case presented below is the third to appear in the English language.Case ReportA 45-year-old Scottish chauffeur was first seen on January 2, 1942, because of abnormal pulmonary shadows on routine x-ray examination of the chest. He had been a . . .
Abstract 730: Identifying the mechanisms of action and resistance to the novel multi-kinase inhibitor ENMD-2076 in leukemia
Authors: Timothy Failes, Gorjana Mitic, Maria Kavallaris
Journal: Cancer Research (2011)

Abstract Background: Molecularly targeted agents such as kinase inhibitors have offered great promise in treatment regimens for cancer. However, the rapid development of resistance to kinase inhibitors mediated through adaptations such as point mutations in the target kinase domain has emerged as a major clinical problem. Accordingly, multi-kinase inhibitors are a promising class of chemotherapeutic agents that can target multiple cytotoxic pathways and potentially be less susceptible to the onset of resistance. ENMD-2076 is a multi-kinase inhibitor that targets Aurora A and multiple receptor tyrosine kinases involved in angiogenesis. ENMD-2076 is showing much promise in Phase I/II clinical trials, yet the specific pathways of sensitivity and resistance are still unclear. Methods: Acute T-cell leukemia CCRF-CEM cells were selected for resistance in 6 µM of ENMD-2076. The resultant resistant cells were designated CEM/AKA6. The level of resistance to the selecting agent was characterized using drug treated cell viability assays. Screening for mutations in Aurora A was conducted using full-length gene sequencing. Real time PCR was used for gene and western blotting for protein expression studies. Phosphoprotein analysis was conducted using Full Moon Biosystems Inc, antibody arrays. Results: CEM/AKA6 cells were 10-fold resistant to ENMD-2076. No significant changes in the gene and protein expression of Aurora A were found compared to the parental cells. Moreover, full-length sequencing of the Aurora A or Aurora B gene failed to detect mutations. CEM/AKA6 cells were as equally sensitive to a specific Aurora A inhibitor, MLN8237, as the parental cells, further suggesting that resistance to ENMD-2076 is not mediated through an Aurora A dependent pathway. ENMD-2076 is known to target the anti-apoptotic PI3K/Akt signaling pathway and CCRF-CEM cells have a deletion in PTEN that leads to constitutive activation of this pathway. Analysis of the Akt pathway using phospho-specific antibody arrays showed that phosphorylation of PDK1, upstream from Akt, was enhanced in CEM/AKA6 cells compared to parental cells, whilst phosphorylation of proteins downstream from Akt such as p53 and c-Jun was decreased. Validation, localization and functional characterization of these protein changes are planned. Conclusions: The PI3K/Akt signaling pathway is altered in leukemia cells resistant to the multikinase inhibitor ENMD-2076. Understanding the interplay of this specific pathway in mediating resistance and/or sensitivity to ENMD-2076 will shed light on the mechanism of this promising agent and may enable optimization of its clinical use. 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 730. doi:10.1158/1538-7445.AM2011-730