tbuckley/cabot-search huggingface dataset:
Elliptocytosis in patients with C-terminal domain mutations of protein 4.1 correlates with encoded messenger RNA levels rather than with alterations in primary protein structure
Authors: Madeleine Morinière, Leticia Ribeiro, Nicole Dalla Venezia, Mireille Deguillien, Philippe Maillet, Thérèse Cynober, François Delhommeau, Helena Almeida, Gabriel Tamagnini, Jean Delaunay, Faouzi Baklouti
Journal: Blood (2000)
Abstract P3-04-03: PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors
Authors: Brian D Lehmann, Joshua A Bauer, Johanna M Schafer, Christopher S Pendleton, Luojia Tang, Kimberly C Johnson, Xi Chen, Justin M Balko, Henry Gomez, Carlos L Arteaga, Gordon B Mills, Melinda E Sanders, Jennifer A Pietenpol
Journal: Cancer Research (2015)

Abstract Triple negative breast cancer (TNBC) is a heterogeneous collection of biologically diverse cancers, which contributes to variable clinical outcomes. Previously, we identified a TNBC subtype that has a luminal phenotype and expresses androgen receptor (AR+). TNBC cells derived from these luminal AR+ tumors have high frequency PIK3CA mutations. The purpose of this study was to determine if targeting PI3K alone or in combination with an AR antagonist is effective in AR+ TNBC. Methods: We determined the frequency of activating PIK3CA mutations in AR+ and AR- TNBC clinical cases. Using AR+ TNBC cell lines and xenograft models we evaluated the effectiveness of PI3K inhibitors, used alone or in combination with an AR antagonist, on tumor cell growth and viability. Results: PIK3CA kinase mutations were highly clonal, more frequent in AR+ vs. AR- TNBC (40% vs. 4%), and often associated with concurrent amplification of the PIK3CA locus. PI3K/mTOR inhibitors had an additive growth inhibitory effect when combined with genetic or pharmacological AR targeting in AR+ TNBC cells. We also analyzed the combination of bicalutamide +/- the pan-PI3K inhibitor GDC-0941 or the dual PI3K/mTOR inhibitor GDC-0980 in xenograft tumor studies and observed additive effects. Conclusions: While approximately one third of TNBC patients respond to neoadjuvant/adjuvant chemotherapy, recent studies have shown that patients with androgen receptor positive (AR+) TNBC are far less likely to benefit from the current standard of care chemotherapy regimens and novel targeted approaches need to be investigated. In this study, we show that activating PIK3CA mutations are enriched in AR+ TNBC; and, the growth and viability of AR+ TNBC cell line models is significantly reduced after treatment with PI3K inhibitors used in combination with an AR antagonist. These results provide rationale for pre-selection of TNBC patients with a biomarker (AR expression) to investigate the use of AR antagonists in combination with PI3K/mTOR inhibitors. Citation Format: Brian D Lehmann, Joshua A Bauer, Johanna M Schafer, Christopher S Pendleton, Luojia Tang, Kimberly C Johnson, Xi Chen, Justin M Balko, Henry Gomez, Carlos L Arteaga, Gordon B Mills, Melinda E Sanders, Jennifer A Pietenpol. PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-03.
Endogenous Myeloperoxidase Is a Mediator of Joint Inflammation and Damage in Experimental Arthritis
Authors: Dragana Odobasic, Yuan Yang, Ruth C. M. Muljadi, Kim M. O'Sullivan, Wenping Kao, Malcolm Smith, Eric F. Morand, Stephen R. Holdsworth
Journal: Arthritis & Rheumatology (2013)

Myeloperoxidase (MPO) is implicated as a local mediator of tissue damage when released extracellularly in many chronic inflammatory diseases. The purpose of this study was to explore the role of endogenous MPO in experimental rheumatoid arthritis (RA).K/BxN serum-transfer arthritis was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO(-/-) ) mice, and disease development was assessed. MPO activity was measured in joint tissues from mice with or without K/BxN arthritis. Collagen-induced arthritis (CIA) was induced in WT and MPO(-/-) mice, and disease development and immune responses were examined. MPO expression was assessed in synovial biopsy samples from patients with active RA, and the effect of MPO on synovial fibroblasts was tested in vitro.MPO was up-regulated in the joints of mice with K/BxN arthritis, and MPO deficiency attenuated the severity of the disease without affecting circulating cytokine levels. In CIA, MPO(-/-) mice had enhanced CD4+ T cell responses and reduced frequency of regulatory T cells in the lymph nodes and spleen, as well as augmented interleukin-17A and diminished interferon-γ secretion by collagen-stimulated splenocytes, without an effect on circulating anticollagen antibody levels. Despite enhanced adaptive immunity in secondary lymphoid organs, CIA development was attenuated in MPO(-/-) mice. Intracellular and extracellular MPO was detected in the synovium of patients with active RA, and human MPO enhanced the proliferation and decreased the apoptosis of synovial fibroblasts in vitro.MPO contributes to the development of arthritis despite suppressing adaptive immunity in secondary lymphoid organs. This suggests distinct effects of local MPO on arthritogenic effector responses.
Abstract P310: Impact of HealthCorps Program on Participating New York City High School Students' Knowledge of Nutrition, Mental Health and Physical Activity
Authors: Moonseong Heo, Erica D Irvin, Natania Ostrovsky, David Lounsbury, Carmen Isasi, Arthur Blank, Tiana Yom, Mindy Ginsberg, Lynn Fredericks, Shawn G Hayes, Judith Wylie-Rosett
Journal: Circulation (2015)

Introduction: HealthCorps provides school wellness programming using curricula to promote changes in nutrition, mental health and physical activity behaviors. The research objective was to evaluate the effect of implementing its curricula on nutrition, mental health and physical activity knowledge and behavior. Hypothesis: That the HealthCorps program has positively effects on student knowledge and health behaviors in 14 public New York City high schools. Methods: Pre- and post-survey data were collected (N=2255) during 2012-13 academic year from New York City public high schools (N=14). An 18-item knowledge survey addressed three domains; 26 behavioral items were analyzed by factor analysis to identify 6 behavior domains, breakfast being a seventh one-item domain. We examined the effects stratified by gender, applying multi-level mixed-effects models to take into account clustering effects of schools and participants adjusted for age. Results: The HealthCorps program significantly increased all three knowledge domains (p&lt;0.05). HealthCorps curricula significantly changed several key behavioral domains. Specifically, among boys, curricula significantly increased fruits/vegetables intake (p=0.03). Among girls, it increased acceptance of new fruits/vegetables (p=0.03), decreased sugar-sweetened beverages and energy dense food intake (p=0.03), but decreased breakfast consumption (p=0.04). The associations between knowledge and behavior were stronger in boys than girls. Conclusion: The HealthCorps program significantly increased participants’ knowledge on nutrition, mental health and physical activity. It also improved several key behavioral domains, which are targets of the 2010 Dietary Guidelines to address obesity in youth.
Abstract 1755: CT053PTSA, a novel c-MET and VEGFR2 inhibitor, potently suppresses angiogenesis and tumor growth
Authors: Ning Xi, Yingjun Zhang, Zhaohe Wang, Yanjun Wu, Tingjin Wang
Journal: Cancer Research (2014)

Abstract Background: In many human cancers, c-Met is activated via receptor overexpression, amplification, mutation and/or a ligand-dependent autocrine/paracrine loop. c-MET-driven tumor growth and metastasis may be further stimulated by hypoxic conditions in the tumor microenvironment, which are often exacerbated by the VEGF-pathway inhibition. Therefore, blockades of c-Met and VEGFR2 simultaneously may yield synergistic inhibition on tumor growth. Methods and Results: CT053PTSA is a potent, orally bioavailable small molecule tyrosine kinase inhibitor (TKI) against c-Met, VEGFR2 as well as Axl, Mer, and FLT3, all of which have been implicated in tumor pathogenesis. In cell-based assays, CT053PTSA showed IC50s of 6.7, 1.9 and &amp;lt; 1.0 nM against c-Met, VEGFR-2 and Axl. In cell-based functional assays, CT053PTSA inhibited HGF and VEGF-stimulated HUVEC proliferation and microvascular angiogenesis in rat aortic rings with IC50 values of 8.6 and 6.3 nM, respectively. When single dosed orally (3mg/kg) to U87MG tumor-bearing nude mice, CT053PTSA potently inhibited the phosphorylation of c-Met and its downstream signaling kinases AKT and ERK1/2 for up to 6 hours in tumor tissues. The antitumor efficacy of CT053PTSA was evaluated in human tumor subcutaneous xenograft models in athymic mice, which included Caki-1 (kidney carcinoma), U-87MG (glioblastoma), NCI-H441 (lung adenocarcinoma), MDA-MB-231 (breast adenocarcinoma), SMMC-7721 (hepatoma), 5637 (bladder carcinoma) and SK-OV-3 (ovarian carcinoma). The ED50s of CT053PTSA to inhibit tumor growth in these studies ranged from &amp;lt; 1mg/kg (NCI-H441) to ∼ 6 mg/kg (SMMC-7721). In orthotopic U87MG human glioblastoma xenograft model, CT053PTSA prolonged the median survival time (MST) and yielded significant increase in life-span value (ILS = 32%, p = 0.003) at an oral dose of 20 mg/kg/day (dosed 21 days) versus the vehicle-treated group. Conclusions: CT053PTSA displayed excellent oral bioavailability (&amp;gt; 60% across animal species) and desirable drug exposures in mice, rats, dogs and monkeys. Based on its potent antitumor activity, favorable PK profile and toxicological data, CT053PTSA was granted to enter clinical trials in China and is currently under phase I evaluation as a potential treatment for human malignancies. Citation Format: Ning Xi, Yingjun Zhang, Zhaohe Wang, Yanjun Wu, Tingjin Wang. CT053PTSA, a novel c-MET and VEGFR2 inhibitor, potently suppresses angiogenesis and tumor growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1755. doi:10.1158/1538-7445.AM2014-1755
Sexually assaultive male juveniles: a follow-up
Authors: M Rubinstein, C A Yeager, C Goodstein, D O Lewis
Journal: American Journal of Psychiatry (1993)

The purpose of this study was to investigate the adult outcome of a group of male juveniles who committed sexual assault.Nineteen sexually assaultive male juveniles and a comparison group of 58 violent juveniles were studied over an 8-year period through use of criminal records and clinical interviews.Although in adolescence the two groups were similarly violent, on follow-up those who had committed sexual assault were significantly more likely to commit adult sexual offenses. They also committed significantly more violent nonsexual offenses. Childhood sexual abuse, especially by females, was associated with adult sexual offenses.Sexually assaultive delinquents are at particularly high risk for subsequent violence. Hence, special efforts must be made to treat these delinquents in adolescence. Prevention of violent sexual behavior must include improved methods of detecting sexual abuse, especially that perpetrated by older females.
Genetic relatedness between group B streptococci originating from bovine mastitis and a human group B streptococcus type V cluster displaying an identical pulsed-field gel electrophoresis pattern
Authors: I.C.M. Oliveira, M.C. de Mattos, T.A. Pinto, B.T. Ferreira-Carvalho, L.C. Benchetrit, A.A. Whiting, J.F. Bohnsack, A.M.S. Figueiredo
Journal: Clinical Microbiology and Infection (2006)
COARCTATION OF THE AORTA, DISSECTING ANEURYSM, AND ANEURYSMAL DILATATION OF THE LEFT VERTEBRAL ARTERY; REPORT OF A CASE
Authors: Linn J. Boyd, S. Charles Werblow
Journal: Annals of Internal Medicine (1937)

Case Reports1 November 1937COARCTATION OF THE AORTA, DISSECTING ANEURYSM, AND ANEURYSMAL DILATATION OF THE LEFT VERTEBRAL ARTERY; REPORT OF A CASELINN J. BOYD, M.D., F.A.C.P., S. CHARLES WERBLOW, M.D.LINN J. BOYD, M.D., F.A.C.P.Search for more papers by this author, S. CHARLES WERBLOW, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-5-845 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough several unusual, indeed, almost unique features alone justify the publication of this case, a more compelling motive, the equally rare correct appraisal of the situation, is responsible. Only 10 per cent of the cases of aortic coarctation have been recognized ante mortem and its discovery at postmortem examination remains a "surprise d'amphitheatre." One of us (L. J. B.) has had the opportunity to make the presumptive diagnosis of coarctation of the aorta twice within two years on the basis of hypertension, marked differences in the blood pressures in the arms and legs, notching of the lower borders of the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication December 30, 1936.From the Department of Medicine, The New York Medical College and Flower Hospital and the Medical Service of the Metropolitan Hospital, New York City. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAnévrisme intracrânien associé à une coarctation de l'aorte: à propos d'un cas et revue de la littératureIntracranial aneurysms associated with unsuspected aortic coarctationThe angiographic demonstration of coarctation of aorta and similar anomaliesUNRUPTURED VERTEBROBASILAR ANEURYSMSAnomalien der Aorta und der A. pulmonalisKrankheiten der GefäßeAneurysmenDissecting Aneurysm of the AortaAneurysmenCoarctation of the aortaTwo cases of dissecting aneurysm of the aorta, with ante-mortem diagnosisDissecting aneurysm of the aortaDissecting aneurysmDissecting aneurysm of the aorta 1 November 1937Volume 11, Issue 5Page: 845-850KeywordsAneurysmsAortaArteriesAutopsyBlood pressureHospital medicineHypertensionMedical services ePublished: 1 December 2008 Issue Published: 1 November 1937 PDF downloadLoading ...
Abstract P387: Cardiovascular Risk Factors Among Children in a 20 year Community Study: Influence of the Family
Authors: Tracy L Nelson, Laura Dvorak, Kathy Kioussopoulos, Gary Luckasen
Journal: Circulation (2012)

Background: High cholesterol, atherosclerosis, high blood pressure, and obesity can be identified during childhood. Identifying the underlying contributors to such risk factors may allow young families the opportunity to modify health habits. The purpose of this study was to determine the prevalence of cardiovascular risk factors and their associated predictors among Northern Colorado children and their families. Methods: The Poudre Valley Health System (PVHS), Healthy Hearts Club has provided a successful cardiovascular screening program for the past ∼20 years (1993–2011) to identify risk factors among students in six Northern Colorado school districts (a primarily white population ∼90%). Schools were selected based on willingness to participate. Data were collected cross-sectionally with objective measures of total cholesterol, high-density lipoprotein cholesterol (HDL-C), blood pressure and body mass index (BMI). Surveys were filled out by the parent and/or legal guardian and included questions about diet and physical activity of the child as well as these behaviors and risk factors among family members. Results: There were 9,363 children with information for the measured risk factors (mean age, 10.4 years, range, 6.2–18 years, 49% female). The prevalence of the six measured risk factors included 39% with total cholesterol &gt; 170 mg/dl, 10.7%, with HDL-C &lt; 35 mg/dl, 11.7% with Cholesterol/HDL ratio &gt;4.8, 7.2% with systolic blood pressure &gt; 120 mmHg, 8.2% with diastolic blood pressure &gt; 80 mmHg and 21.1% with BMI &gt; 85 percentile for age and sex. There were 40.8%, 35%, 14.5%, 6.2%, 2.4%, 0.8% and 0.2% with 0–6 risk factors respectively. Of those with zero risk factors 25.7% reported a family member (other than the child) being overweight while 68.2% reported such among those with five risk factors; similarly 16.4% reported a family member who smokes (among children with zero risk factors) as compared to 24% with five risk factors. High cholesterol, high blood pressure and diabetes trended similar. Conclusions: The prevalence of CVD risk factors among these children is substantial and is associated with such risk factors among the family. This data suggests risk factor reduction must not be done in isolation of the family.
A Code of Ethics for Ethicists: What Would Pierre Bourdieu Say? “Do Not Misuse Social Capital in the Age of Consortia Ethics”
Authors: Vural Özdemir, Hakan Kılıç, Arif Yıldırım, Effy Vayena, Edward S. Dove, Kıvanç Güngör, Adrian LLerena, Semra Şardaş
Journal: The American Journal of Bioethics (2015)

Social capital is the aggregate of the actual or potential resources which are linked to possession of a durable network of more or less institutionalized relationships of mutual acquaintance and r...
1028. Virus-Mediated RNAi for Skp-2 in Human Small Cell Lung Carcinoma Cells Resulted in the Inhibition of Tumor Cell Growth through the Increase of p27Kip1 and p21
Authors: Hidetoshi Sumimoto, Shizuko Yamagata, Ayako Shimizu, Makoto Miyagishi, Hiroyuki Miyoshi, Kazunari Taira, Yutaka Kawakami
Journal: Molecular Therapy (2004)
Abstract 2690: Sorafenib/regorafenib and phosphatidyl inositol 3 kinase/thymoma viral proto-oncogene inhibition interact to kill tumor cells
Authors: Larry A. Booth, Nichola A. Cruickshanks, G B. Sajithlal, Hossein A. Hamed, Seyedmehrad Tavallai, J Syed, Steven Grant, Andrew Poklepovic, Paul Dent
Journal: Cancer Research (2014)

Abstract The present study aimed to determine whether the multikinase inhibitors, sorafenib/regorafenib, worked in conjunction with PI3K/AKT inhibitors to enhance tumor cell death. It has been noted that combination of sorafenib/regorafenib with a PI3K inhibitor acetic acid (PX-866) resulted in tumor cell death, in a greater than additive fashion, in liver, colorectal, lung, breast, kidney and brain cancer cells. Similar data was obtained using AKT inhibitors perifosine and MK2206. Furthermore, even cells lacking PTEN remained as sensitive to this combinational approach as cells expressing PTEN. PX-866 treatment abolished AKT/GSK3 phosphorylation, with tumor cell death correlating with reduced activity of AKT and mTOR. Expression of activated AKT and to a lesser extent activated mTOR reduced drug combination lethality. Expression of B-cell lymphoma-extra large or dominant negative caspase 9, but not cellular FLICE-inhibitory protein short, protected cells from the drug combination. Treatment of cells with PX-866 increased protein levels of p62, LAMP2 and LC3/LC3II which correlated with the resulting increase in LC3-GFP vesicle numbers. Exposure of PX-866 treated cells to sorafenib reduced p62 and LAMP2 levels, decreased the ratio of LC3 to LC3II and reduced LC3-GFP vesicle levels. Knockdown of Beclin1 or ATG5 suppressed drug toxicity by ∼40%. In vivo, combination of either sorafenib and PX-866 or regorafenib and MK2206 cooperated to suppress the growth of established HuH7 and HCT116 tumors, respectively. Collectively our data demonstrates that the combination of sorafenib family kinase inhibitors with inhibitors of the PI3K/AKT pathway kills tumor cells in vitro and in vivo. Citation Format: Larry A. Booth, Nichola A. Cruickshanks, G B. Sajithlal, Hossein A. Hamed, Seyedmehrad Tavallai, J Syed, Steven Grant, Andrew Poklepovic, Paul Dent. Sorafenib/regorafenib and phosphatidyl inositol 3 kinase/thymoma viral proto-oncogene inhibition interact to kill tumor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2690. doi:10.1158/1538-7445.AM2014-2690
Mass RNA analysis using stool in colorectal cancer
Authors: Ryung Ah Lee, Eun-Joung Lee, Eun Jung Ahn
Journal: Clinical Cancer Research (2006)

A29  (Background) It has been estimated that approximately 1010 of normal adult colonic epithelial cells, each having a lifespan of 3-4days, are shed daily from the lower two-thirds of colon crypts; thus, using colonocytes to develop a screening test is an attainable goal. There is a need for sensitive and specific diagnostic and prognostic molecular markers which can monitor early patterns of gene expression in non-invasive exfoliated colonocytes shed in the stool. There were a few studies of RNA -based detection method because of the characteristics in stool. We report here the mass RNA analysis using stool in colorectal cancer. (Method) The study included 15 patients with colorectal cancer, and 15 control patients without neoplastic disease of the colon and rectum. RNA was isolated from routinely collected stool samples using a modified method. The expression levels of survivin, livin, Akt-1, caveolin, histone deacetylase(HDAC)1, matrix metalloproteinases(MMP)-2, MMP-7, MMP-9, MMP-12, hepatoma derived growth factor(HDGF), peptideYY, hypoxia-inducible factor(HIF)-1, epidermal growth factor receptor(EGFR), N-cadherin, catenin-β, inducible nitric oxide synthase(iNOS), ring-3, enolase-1α, insulin-like growth factor binding protein(IGFBP)-2, tissue inhibitors of metalloproteinase(TIMP)-1 and EphB2 were determined by reverse-transcription polymerase chain reaction(RT-PCR). (Result) The sensitivity of fecal survivin, livin and Akt-1 assays for colorectal cancer was 93%, whrereas sensitivity of the fecal caveolin, HDAC1, MMP-2, HDGF and peptideYY assays for colorectal cancer was 13%, 6%, 20%, 6% and 6%, respectively. The remained 13assays were not shown any expression in both colorectal and normal group. The expression levels of survivin, livin and Akt-1 were higher in colorectal cancer group than normal group(p
Treatment of cavitary and infiltrating pulmonary tuberculosis with and without the immunomodulator Dzherelo
Authors: S.I. Zaitzeva, S.L. Matveeva, T.G. Gerasimova, Y.N. Pashkov, D.A. Butov, V.S. Pylypchuk, V.M. Frolov, G.A. Kutsyna
Journal: Clinical Microbiology and Infection (2009)