tbuckley/cabot-search huggingface dataset:
Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo
Authors: Naoki Wakimoto, Dong Yin, James O'Kelly, Talin Haritunians, Beth Karlan, Jonathan Said, Hongtao Xing, H. Phillip Koeffler
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3284 

Purpose: Cucurbitacins are a group of diverse triterpenoid substances isolated from plants with medicinal properties. One particularly potent family member is cucurbitacin B (CuB). The antiproliferative effects of CuB against human breast cancer cells were tested.    Experimental Design: Six human breast cancer cell lines were examined because they represent a diverse mix of breast cancer subtypes varying in expression of estrogen receptor (ER), Her2/neu, and p53 mutation. The antiproliferative effect of CuB were also studied in vivo .    Results: The effective dose inhibiting 50% growth (ED50) was between 10-8 M and 10-7 M for this collection of breast cancer cell lines. These cells underwent rapid morphologic changes after 15 to 20 minutes exposure to CuB (5 x 10-7 M), which was associated with disruption of the microtubules and F-actin, as observed by confocal microscopy. Human MDA-MB-231 (ER-, p53 mutated) breast cancer cells were orthotopically implanted into the breasts of nude mice who intraperitoneally received either CuB 1.0 mg/kg or vehicle. Tumor volume was reduced by 55% in the group that received CuB for 6 weeks compared to vehicle controls. No apparent organ tissue damage was observed by pathological assessment. Interestingly, the experimental mice had lower serum glucose levels, consistent with use of CuB as an anti-diabetic drug in China. Conclusion: This drug appears to be a third in a family of drugs targeting the microtubules [taxanes (e.g. taxol), vinca alkaloid (e.g. vincristine), and now CuB]. Our in vitro and in vivo results suggest that CuB may be an effective, new approach for the treatment of ER-, Her2/neu amplified, and p53 mutant breast cancers.
Substance abuse among patients with treatment-resistant schizophrenia: characteristics and implications for clozapine therapy
Authors: P Buckley, P Thompson, L Way, H Y Meltzer
Journal: American Journal of Psychiatry (1994)

The goals of this study were 1) to determine the extent of substance abuse in patients with treatment-resistant schizophrenia and 2) to assess the relevance of such abuse to subsequent response to treatment with clozapine.The subjects were 118 treatment-resistant patients with DSM-III-R diagnoses of schizophrenia or schizoaffective disorder who underwent detailed demographic, clinical, and psychopathological evaluations before commencing treatment with clozapine. Lifetime and current histories of substance abuse were also systematically evaluated and characterized according to the Research Diagnostic Criteria and DSM-III-R. Response to clozapine treatment at 6 months was determined with measures of psychopathology and psychosocial function.An antecedent or current history of substance abuse was determined for 29 patients. Although predominantly male, the abusers did not differ from the nonabusers on other demographic features. The substance abusers actually showed less psychopathology (negative and disorganization symptoms) and better psychosocial functioning at baseline; however, both groups attained similar improvements on these measures after 6 months of clozapine therapy.A modest extent of previous or current substance abuse was observed among neuroleptic-resistant schizophrenic patients who subsequently received treatment with clozapine. This antecedent history of substance abuse did not appear to negatively influence subsequent response to clozapine treatment.
Atrial Myocardial Deformation Properties Predict Maintenance of Sinus Rhythm After External Cardioversion of Recent-Onset Lone Atrial Fibrillation
Authors: Giovanni Di Salvo, Pio Caso, Rosalia Lo Piccolo, Angela Fusco, Alfonso R. Martiniello, Maria G. Russo, Antonio D’Onofrio, Sergio Severino, Paolo Calabró, Giuseppe Pacileo, Nicola Mininni, Raffaele Calabró
Journal: Circulation (2005)

Accurate echocardiographic parameters to predict maintenance of sinus rhythm in patients with atrial fibrillation (AF) are poorly defined. This study was conducted to assess the atrial myocardial properties during AF through myocardial velocity, strain rate, and strain and to compare their prognostic value in maintaining sinus rhythm in patients with lone AF with standard transthoracic (TTE) and transesophageal echocardiography (TEE).Sixty-five consecutive patients with lone AF for < or =3 months underwent TTE, TEE, and myocardial velocity and strain and strain rate imaging examinations before successful external cardioversion. Maintenance of sinus rhythm was assessed during a 9-month follow-up. Atrial myocardial velocity, strain, and strain rate values in AF patients were compared with those of age- and sex-matched referents. Moreover, clinical and echocardiographic parameters of patients with maintenance of sinus rhythm (MSR patients) over the 9-month follow-up period (n=25) were compared with those from patients with AF recurrence (AFR patients; n=40). Atrial myocardial properties assessed by myocardial velocity, strain rate, and strain were significantly reduced (P<0.0001) in patients (velocity, 3.2+/-1.4 cm/s; strain, 23.3+/-19%; strain rate, 2+/-0.9 seconds(-1)) compared with referents (velocity, 5.7+/-1.3 cm/s; strain, 92+/-26%; strain rate, 4.2+/-1.8 seconds(-1)). The individual predictors of sinus rhythm maintenance were atrial appendage flow velocity (MSR patients, 39+/-12 cm/s; AFR patients, 32+/-15 cm/s; P<0.01) assessed by TEE and atrial strain (MSR patients, 33+/-27%; AFR patients, 17+/-9%; P=0.0007) and strain rate (MSR patients, 2.7+/-1 seconds(-1); AFR patients, 1.6+/-0.6 seconds(-1); P<0.0001) peak systolic values. Atrial strain (P<0.0001; coefficient, 0.015; SE, 0.003) and strain rate (P<0.0001; coefficient, 0.372; SE, 0.075) parameters alone were confirmed as independent predictors of sinus rhythm maintenance by multivariable analysis.Patients with higher atrial strain and strain rate appear to have a greater likelihood of staying in sinus rhythm. If the current data are verified in future studies, then additional pharmacological therapy and maintenance of anticoagulants for a longer period may need to be considered in those with lower atrial strain and strain rate measurements.
Drug delivery system may combat cancer
Authors: Abi Berger
Journal: BMJ (2001)

Encapsulating cancer treatment within immunoprotected “factories” seems to greatly enhance the efficacy of treatment of malignant brain tumours in rats. Scientists have reported a new way of treating brain tumours that improves survival rates and may lead to less toxic doses of treatment being used ( Nature Biotechnology 2001;19:29-34).

Most tumours grow by developing a network of new blood vessels to …
PRESENILE PSYCHOSIS OF THE JAKOB TYPE
Authors: GEORGE A. JERVIS, HERMAN M. HURDUM, FRANCIS J. O'NEILL
Journal: American Journal of Psychiatry (1942)

The case of a man aged 53 is described, who showed an organic type of dementia accompanied by wasting and fibrillation of the muscles of the upper extremities. The course of the disease was rapidly downhill with increasing mental deterioration and marked muscular wasting, extending to the lower extremities. Vitamin E therapy was used without apparent effect. The duration of the disease was about one year. Pathologically, there were widespread lesions of the neuron cells extending to the cerebral cortex, the basal ganglia and particularly the motor cells of the medulla and spinal cord. The neuroglia was hyperplastic and hypertropic; the microglia had also proliferated and numerous rod-shaped cells were observed. The case is considered an instance of presenile psychosis of the Jakob's type (cortico-striato-spinal degeneration). The few similar cases reported in the literature are summarized and some clinical, pathologic and etiologic aspects of the disease are briefly discussed.
Abstract MS1-1: Characterising cancer risks for carriers of mutations in BRCA1, BRCA2, PALB2, and RAD51C genes
Authors: Antonis C. Antoniou
Journal: Cancer Research (2015)

Abstract The presentation will provide an overview of the latest developments and challenges in understanding the penetrance of mutations in the BRCA1, BRCA2, PALB2 and RAD51C genes. Genetic counselling currently relies on average cancer risk estimates obtained from retrospective penetrance studies involving large numbers of families segregating mutations in these genes. The talk will present penetrance estimates from ongoing prospective analyses, based on data from the International BRCA1/2 Carrier Cohort Study, the largest cohort of BRCA1/2 mutation carriers worldwide that includes &amp;gt;10,000 mutation carriers at baseline with prospective follow-up information. Several common alleles and other risk factors have now been shown to modify breast cancer risk for BRCA1 and BRCA2 mutation carriers. The talk will review the latest efforts and results from the Consortium of Investigators of Modifiers of BRCA1/2 to identify genetic modifiers of risk and provide individualised cancer risks for BRCA1 and BRCA2 mutation carriers on the basis of polygenic risk scores. We will also present penetrance estimates based on analyses of combined data from families segregating mutations in PALB2 and RAD51C, the largest efforts of their kind. Finally the presentation will demonstrate how the effects of common and rare breast cancer susceptibility variants are incorporated into the BOADICEA model to provide comprehensive risks of developing breast cancer in the future. Citation Format: Antonis C. Antoniou. Characterising cancer risks for carriers of mutations in BRCA1, BRCA2, PALB2, and RAD51C genes [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 MS1-1.
Abstract P219: Lesser LDL Drop on Statins Predicts Greater Glycemic Rise in Women
Authors: Beatrice A Golomb, Alexis K Bui
Journal: Circulation (2015)

Background: Statins elevate glucose (glc) in some people, but effects vary. Age & metabolic syndrome precursors were previously shown to significantly predict glc rise on statins (vs placebo) in men but not women. Better understanding of predictors in women is needed. Higher baseline LDL and lesser drop in LDL on statins was previously linked to more muscle symptoms on statins - postulated to arise from LDL upregulation for antioxidant transport in prooxidant settings - which might also lead to glc elevation. Goal: To assess the relation of LDL (baseline and change-on-statins) to glc change (Δglc) in women. Method: 324 postmenopausal women, without known diabetes or CVD, with fasting glc ≤142mg/dL, LDL 115-190 mg/dL, underwent (sex-stratified, double-blind) randomization to pravastatin 40mg, simvastatin 20mg or placebo for 6 months. 203 were age<65. Regression assessed prediction of Δglc by statin-vs-placebo, baseline and ΔLDL, adjusted for baseline-glc§. Analysis was repeated, stratified by treatment arm...
Drug use in prison
Authors: S. M Gore, S. Seaman
Journal: BMJ (1996)

Table 1-Prevalence of antibody to H pyloni and C pneumoniae in patients with acute myocardial infarction and controls.Figures are numbers (percentages) Patients with acute myocardial infarction (n = 37) Controls (n = 60) C pneumonlae C pneumonlae C pneumonlse C pneumonlae positive negative positive negative H pylon positive 28 (76) 4 (11) 12 (20) 20 (33) H pylori negative 3 (8) 2 (5) 18 (30) 10 (17)bacteria, mediated by IgE, could be responsible for the enhanced production of interleukin 6.The intense proinflammatory and procoagulant properties of this cytokine could account for most, if not for all, acute coronary syndromes.
25-hydroxycholesterol induces mitochondrial DNA damage and dysfunction in the human leukemic CEM cells.
Authors: Maria del Rocio Castro, Nydia Rosario, Karina Acevedo-Torres, Carlos Torres-Ramos, Sylvette Ayala-Torres
Journal: Cancer Research (2007)

1969  Oxysterols are cholesterol oxidation products that potently induce apoptosis in human lymphoid cells and therefore have great potential as chemotherapeutic agents.The mechanism(s) by which oxysterols trigger apoptosis in these cells is unknown but radical oxygen species (ROS) generation has been suggested to play a role during oxysterol-induced apoptosis of various cell lines. Within cells, ROS are highly toxic and can damage macromolecules of cells and mitochondria, leading to cell death. In this work we sought to test the hypothesis that oxysterol-induced apoptosis leads to mtDNA damage and loss of mitochondrial function. We applied a quantitative polymerase chain reaction (QPCR) assay to assess the relative amounts of mtDNA damage after oxysterol treatment of the human leukemic cell line CEM. The QPCR assay is based on the principle that oxidative DNA damage such as strand breaks, base modifications and abasic sites block the progression of any thermostable PCR polymerase on the DNA template, resulting in a decrease in amplification of a target DNA sequence. Our data show a time and dose-dependent increase in the number of mtDNA lesions in oxysterol-sensitive CEMC7 cells exposed to 25-hydroxycholesterol (25OHC). A significant 15% decrease in the amplification of a 10.0 kb mitochondrial DNA (mtDNA) fragment was observed at 24 h after 1000 nM 25OHC exposure and an 11%, 21%, and a 35% reduction at 48 h after exposure to 100 nM, 300 nM, and 1000 nM 25OHC, as compared to control values. The number of lesions in a nuclear DNA (nDNA) fragment was less as compared to mtDNA as shown by an 18% reduction of amplification of the nDNA fragment at 48 h after 1000 nM 25OHC treatment vs. a 35% reduction in mtDNA. Our data also show a dose-dependent decrease in ATP levels in the oxysterol-sensitive CEMC7 cells 48 h after exposure to 25OHC (20% and 50% reduction after 300 nM and 1000nM 25OHC, respectively). In addition, we show that in oxysterol-sensitive CEMC7 cells, 25OHC treatment elicits a dose-dependent loss of mitochondrial membrane potential 48 h after 25OHC exposure (25%, 45%, and 60% reduction after 100 nM, 300 nM, and 1000 nM 25 OHC, respectively). The loss of mitochondrial function is not due to a reduction in mitochondrial mass, as demonstrated by measuring the cardiolipin content of mitochondria. These effects were not observed in the oxysterol-resistant M10R5 cells, which do not undergo apoptosis in the presence of 25OHC. These results support our hypothesis that mitochondria are target of oxidative damage during oxysterol-induced apoptosis of human CEM cells and suggest a possible role for mtDNA damage in apoptosis. This work was supported by 2 G12RR030335-16 from NIH-NCRR.
The assessment of the effect of changes in lung cancer follow-up period to the quality of life by using EQ-5D questionnaire and follow data (the project of AKAYAK-1)
Authors: Kader Kiyar Gursul, Ahmet Emin Erbaycu, Tuncay Goksel, Erhan Eser, Burcu Basarik, Aysen Oz, Pinar Celik, Ebru Cakir Ediz, Osman Hatipoglu, Bedriye Atay Yayla, Sevin Baser, Hakan Baydur
Journal: European Respiratory Journal (2013)

The main purpose of the treatment in lung cancer should generally be palliation of symptoms and improvement in quality of life. EURO-QOL (EQ-5D) is a self-report measure of overall quality of life scale.  To investigate the reliability, validity and feasibity of the Turkish version of the EQ-5D questionnaire as a tool for the assessment of quality of life in lung cancer patients in Turkish society.  A multicenter prospective study is carried as a Lung Cancer Association Project in collaboration with Turkish Thoracic Society, Lung and Plavral Malignancies working group and Health and Quality of Life Society.  Of 266 patients, 248 (93.2%) were male and the mean age was 61.3 years. 58.7% of the cases were stage IV, 23.9% of them were stage IIIB. 37.9% of the patients had squamous cell lung carcinoma, 24.2% had adenocarcinoma, and 21.2% had small cell lung carcinoma. 75.9% of the patients had chemotherapy alone. EQ-5D index score at the time of diagnosis has found as moderate reliable measurement, and the measurement of the score at during 3rd and 5th chemotherapy ,after the radiotherapy was found to be highly reliable measurements. EQ-5D questionnaire was found to be consistent in itself. EQ-5D VAS score evaluation, at time of diagnosis, 3rd Cure, 5th Cure and after radiotherapy was found to correlate with each other. Working model fulfills its’ conditions for 6-fit index so EQ-5D scale was found valid.  The psychometric properties of the Turkish version of the EQ-5D questionnaire is a valid and reliable scale for the quality of life in patients with lung cancer in Turkey and that can be used safely in the clinic.
The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B
Authors: Liang Peng, Qiang Zhao, Qibin Li, Miaoxin Li, Caixia Li, Tingting Xu, Xiangyi Jing, Xiang Zhu, Ye Wang, Fucheng Li, Ruihong Liu, Cheng Zhong, Qihao Pan, Binghui Zeng, Qijun Liao, Bin Hu, Zhao‐xia Hu, Yang‐su Huang, Pak Sham, Jinsong Liu, Shuhua Xu, Jun Wang, Zhi‐liang Gao, Yiming Wang
Journal: Hepatology (2014)

In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium–taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status ( P = 5.7 × 10 −23 , odds ratio = 0.36) irrespective of hepatitis B virus surface antibody status ( P = 6.2 × 10 −21 and 1.5 × 10 −10 , respectively, when the cases were compared with hepatitis B virus surface antibody–positive and –negative controls). The variation was also associated with a lower incidence of acute‐on‐chronic liver failure ( P = 0.007). The estimated heritability explained by this single variation was ∼3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. Conclusion : The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute‐on‐chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection. (H epatology 2015;61:1251–1260)
Abstract 12166: Efficacy of Low-dose Aspirin Therapy for Primary Prevention of Atherosclerotic Events Depends on the Severity of Diabetes: a subanalysis of JPAD trial
Authors: Sadanori Okada, Takeshi Morimoto, Hisao Ogawa, Masafumi Nakayama, Mio Sakuma, Shiro Uemura, Masao Kanauchi, Naofumi Doi, Hideaki Jinnouchi, Hirofumi Soejima, Seigo Sugiyama, Masako Waki, Takahiro Kawano, Yoshihiko Saito
Journal: Circulation (2010)
Multisite data reanalysis of the validity of rapid cycling as a course modifier for bipolar disorder in DSM-IV
Authors: M S Bauer, J Calabrese, D L Dunner, R Post, P C Whybrow, L Gyulai, L K Tay, S R Younkin, D Bynum, P Lavori
Journal: American Journal of Psychiatry (1994)

The validity of rapid cycling as a distinct course modifier for bipolar disorder was assessed by comparing patients with and without a history of rapid cycling (4 or more affective episodes in 12 months) on demographic, clinical, family history, and outcome variables. These data were also used to formulate operational criteria for the modifier. Data on subjects with rapid-cycling (N = 120) and nonrapid-cycling (N = 119) bipolar disorder from four sites were pooled and analyzed by using case-control and historical cohort methods. The rapid-cycling group contained more women and more subjects from higher social classes than the nonrapid-cycling group. Family history did not differ between the groups. The diagnosis had predictive validity in that the rapid-cycling patients had more episodes than the nonrapid-cycling patients during prospective follow-up. The relationship between gender and episode frequency supported the validity of the cutoff point of 4-8 episodes per year. The data regarding whether patients with rapid cycling based on truncated episodes more closely resembled rapid-cycling or nonrapid-cycling patients were equivocal. Patients whose only rapid cycling was associated with antidepressants resembled spontaneously rapid-cycling patients, while the majority of spontaneously rapid-cycling patients also had periods of antidepressant-associated rapid cycling. The validity of rapid cycling as a distinct course modifier for bipolar disorder is supported by differences in gender, prospectively assessed outcome, and perhaps social class between rapid-cycling and nonrapid-cycling patients. The relationship of gender to episode frequency supports the cutoff of 4 or more episodes per year.
Abstract 13722: Dual Roles of cAMP In Cardiac Myocyte Apoptosis Induced by Beta-Adrenergic Agonists
Authors: Xiaoying Zhang, Xiaojie Ai, Mingxin Tang, Yingxin Li, Hui Gao, Fang Wang, Xinyi Ge, Catherine Makarewich, Kathryn Stockbower, Xiongwen Chen
Journal: Circulation (2011)

β-Adrenergic (β-AR) overstimulation causes cardiomyocyte death contributing to heart disease development. Protein kinase A (PKA), exchange protein directly activated by cAMP (EPAC) and Ca2+/calmodu...
Abstract 18202: Multiple Arterial Grafts Improve Late Survival of Patients Undergoing CABG: Analysis of 8,622 Patients with Multivessel Disease
Authors: Chaim Locker, Hartzell V Schaff, Joseph A Dearani, Lyle D Joyce, Kevin L Greason, Zhuo Li, Richard C Daly
Journal: Circulation (2011)

Objectives. The use of the left internal mammary artery (IMA) in revascularization of multivessel coronary artery disease has been shown to improve survival following coronary artery bypass graft surgery (CABG), however the incremental survival benefit of multiple arterial grafts is still debated. Methods. We reviewed outcome of 8,622 pt that had isolated primary CABG for multivessel disease from 1993 to 2009.Pt were stratified according to the number of arterial grafts; (1) single IMA plus saphenous vein (SV) IMA/SV group (n=7,435; 83% 3VD) and (2) multiple arterial (MultArt) group (n=1,187; 74% 3VD) Results. Early mortality rate was 0.8% (n=10) in the MultArt group and 2.1% (n=154) in the IMA/SV group (P=0.004). However, the difference was not statistically significant (P=0.996) after adjusting for age, gender, chronic lung disease, renal failure, PVD, MI, EF, and number of diseased vessels. Late survival was significantly greater for the MultArt group compared to IMA/SV group (5-, 10- and 15-year survival rates were 95%, 84% and 71% versus 85%, 61% and 35% p&lt;0.001). MultArt subgroups with the use of bilateral internal mammary artery (BIMA)/SV (n=589) and BIMA only (n=271), had significantly improved 15-years survival (97%, 86%, 76% and 94%, 82%, 75% at 5-, 10- and 15-years, p&lt;0.001), and BIMA/RA (n=147) and LIMA/RA (n=169), had significantly greater 10-years survival (95%, 84% and 93%, 78% at 5- and 10-years, p&lt;0.001) compared to IMA/SV group. In multivariate analysis, use of multiple arterial grafts remained a strong independent predictor of survival (HR=0.78, 95% CI 0.66 - 0.93, p=0.006). Conclusion. Use of the right IMA or radial artery in addition to the left IMA is associated with significantly better overall and late survival compared with single IMA and saphenous vein in patients with two and three-vessel disease undergoing isolated CABG.