tbuckley/cabot-search huggingface dataset:
Abstract #3: Molecular target for dietary prevention of chronic breast cell carcinogenesis
Authors: Hwa-Chain Wang, Xiaoyu Song, Nalin Siriwardhana
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

This study is to identify molecular targets for dietary grape seed proanthocyanidin extract (GSPE) in early prevention of chronic breast cell carcinogenesis induced by environmental carcinogens. Carcinogenesis of human breast epithelial cells from non-cancerous to precancerous and cancerous stages is a multiyear, multistep, and multipath disease process. Epidemiologic and experimental evidence suggests that dietary constituents in fruits and vegetables prevent human cancers. However, the mechanisms for dietary prevention of precancerous carcinogenesis induced by chronic exposure to environmental carcinogens remain to be elucidated. To investigate dietary prevention of chronic human breast cell carcinogenesis, we studied cellular and molecular target endpoints by long-term exposure of human breast epithelial cells to environmental pollutions with low doses of carcinogens. Immortalized, non-cancerous human breast epithelial MCF10A cells were repeatedly exposed to combined carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), each at picomolar concentrations, to induce increasing acquisition of cancer-related cellular and molecular changes. We then used these cellular and molecular changes as target endpoints to reveal the activity of dietary GSPE in suppression of NNK- and B[a]P-induced cellular carcinogenesis. Using siRNAs to knock down gene expression, we verified the role of identified molecular targets in cellular acquisition of cancer-related properties. Our approach provides a human breast, precancerous carcinogenesis-cellular model to serve as a cost-efficient, in vitro system equipped with cellular and molecular target endpoints to identify bioactive dietary components that suppress human breast cell carcinogenesis in order to reduce the health risk of breast cancers caused by long-term exposure to carcinogens in environmental pollution.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3.
Physical health of people with severe mental illness
Authors: W. Barr, P. van de Hoef, I. Colls, R. Scheurer, J. McGrath, H. Whiteford
Journal: BMJ (2001)

Editor—In their editorial Phelan et al correctly highlight the importance of general practitioners assessing the physical health of patients with severe mental illness.1 Although we share their belief that the success of this is reliant on practices identifying these patients, our research suggests that this task is far from straightforward.

Our three year study was sited in an English health district where the NHS trust and health authority had collaborated in establishing registers of cases of severe and enduring mental illness in over 60 general practices.2 The aim was to identify all practice patients with severe mental illness as a first step in raising their profile in practices. Each practice had been allocated a named community mental health nurse, and these link nurses were given a key role in developing the mental health registers in consultation with general practitioners and practice staff. During the study we carried out 42 in depth interviews with the professional staff participating in drawing up and maintaining the mental health registers in six sample practices.

The most striking finding was the difficulty encountered in achieving consistency in defining the characteristics that constitute severe mental illness. Criteria for mental health registration in all practices were drawn from the definition of severe mental illness given by the Department of Health.3 This definition is based on the dimensions of safety, informal or formal care, diagnosis, disability, and duration of illness, but we found it to be susceptible to widely varying interpretation by all participants.4 A second common feature was the impact of pressure of work and staffing shortages on establishing registers: the time consuming procedure of collating accurate and up to date patient data and establishing agreement on inclusion on the register was frequently sacrificed to more pressing matters.

Improving the physical health of severely mentally ill patients is a complex issue. The introduction of mechanisms, such as practice based mental health registers, to help in identifying needy patients is important but will be achieved only as part of an overall strategy that entails adequate staffing levels and shared commitment to the task.
Deregulated apoptosis in ataxia telangiectasia: association with clinical stigmata and radiosensitivity.
Authors: E Duchaud, A Ridet, D Stoppa-Lyonnet, N Janin, E Moustacchi, F Rosselli
Journal: Cancer Research (1996)

Ataxia telangiectasia (AT) is a recessive genetic disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation hypersensitivity, and increased predisposition to cancer. Reduced or delayed induction of the tumor suppressor protein p53 after gamma -irradiation was reported. These characteristics may be compatible with an inability to correctly regulate apoptosis. We show here that AT lymphocytes and EBV-transformed lymphoblasts demonstrate a significantly higher level of spontaneous apoptosis, whereas ionizing radiation-induced apoptosis is reduced compared to normal cells. However, neither AT nor normal primary fibroblasts undergo apoptosis after irradiation. Consequently, we conclude that the radiosensitivity of the AT cells is not related to an increased apoptotic response. Finally, we show that SV40-transformed AT fibroblasts undergo gamma- ray-induced apoptosis, while SV40-transformed normal cells do not. This result raises the question of the physiological relevance of the latter cellular model with respect to the AT phenotype.
Abstract 12922: Cardiac Histone Deacetylase 6 Activity is Critical for Disease Progression in Desmin-Related Cardiomyopathy
Authors: Atsushi Sanbe, Noriko Miyauchi, Hideo Nishigori, Akito Tanoue
Journal: Circulation (2010)

Background: An arg120gly (R120G) missense mutation in crystallin, alpha B (CRYAB), a member of the small heat shock protein family, causes desmin-related cardiomyopathy (DRM), which is characterized by the formation of aggresomes containing CRYAB and desmin. Although it is known that small aggregates are retrogradely transported via the microtubule network to form these aggresomes around nuclei, and that these aggresomes are associated with cardiac disease in DRM, the mechanisms underlying the aggresomal formation remain uncertain. Methods and Results: Aggresomal formation due to mutant CRYAB was analyzed in neonatal rat cardiomyocytes. Overexpression of CRYAB R120G induced by an adenoviral transduction system led to the development of CRAYB-positive aggresomes around nuclei with a concomitant reduction in cell viability in the myocytes. Overexpression of the mutant CRYAB increased acetylated tubulin levels and reduced tubulin deacetylation activity in the myocytes, suggesting that tubulin deacetylating a...
Shorter moxifloxacin-based regimens for drug-sensitive tuberculosis
Authors: Jan-Willem Alffenaar, Tawanda Gumbo, Rob Aarnoutse
Journal: New England Journal of Medicine (2015)

To the Editor: Gillespie et al. (Oct. 23 issue)1 report that two moxifloxacin-containing regimens for the treatment of tuberculosis were not effective with a shortened treatment period of 4 months. The authors used a moxifloxacin dose of 400 mg per day, which may have contributed to the unfavorable results. Rifampin decreases the average exposure to moxifloxacin (assessed according to the area under the curve [AUC]) by approximately 30%,2 which can be compensated for by an increase in the dose of moxifloxacin.3 In addition, preclinical data combined with pharmacokinetic and pharmacodynamic modeling showed that a higher moxifloxacin dose, of 800 mg per day, is likely to achieve better Mycobacterium tuberculosis microbial killing and suppression of drug resistance.4 Limited data have shown that moxifloxacin at a dose of 800 mg can be given safely.3,5 The inclusion of moxifloxacin drug exposure as a covariate would have been of additional value, considering that the ratio of the AUC to the minimum inhibitory concentration is the driver of moxifloxacin efficacy and that the AUC for moxifloxacin can vary among patients by a factor of 7.6 Such a pharmacokinetic and pharmacodynamic analysis could have shown whether the results of this trial could have been explained by a drug exposure to moxifloxacin that was too low.
Gata2 Is a Direct Target for Smad-Mediated TGFβ Signaling in Hematopoietic Stem/Progenitor Cells
Authors: Matilda Nifelt Hägerström, Emma Rörby, Gillian May, Alex Tipping, John Brown, Göran Karlsson, Tariq Enver, Stefan Karlsson
Journal: Blood (2011)
Control of Plasmodium falciparum erythrocytic cycle: γδ T cells target the red blood cell–invasive merozoites
Authors: Giulia Costa, Séverine Loizon, Marianne Guenot, Iulia Mocan, Franck Halary, Geneviève de Saint-Basile, Vincent Pitard, Julie Déchanet-Merville, Jean-François Moreau, Marita Troye-Blomberg, Odile Mercereau-Puijalon, Charlotte Behr
Journal: Blood (2011)
Abstract P008: Ultra-Sensitive Troponin I Strongly Predicts Incident Coronary Heart Disease in the General Population Independently of Traditional Risk Factors. Results From the MONICA/KORA Augsburg Case-Cohort Study
Authors: Wolfgang Koenig, Astrid Zierer, Mahir Karakas, Christa Meisinger, Annette Peters, John Todd, Christian Herder, Barbara Thorand
Journal: Circulation (2014)

Background: High-sensitive (hs) troponin T and I assays as well as ultrasensitive (us) troponin I enable measurement of troponins in 65% to 98% of the general population. We prospectively investigated whether increased concentrations of us-troponin I are associated with an increased risk of coronary heart disease (CHD) after controlling for traditional risk factors. Methods: We conducted a population-based case cohort study in middle-aged healthy men and women within the MONICA/KORA Augsburg studies. Serum levels of us-troponin I (Single Molecule Counting technology, Singulex) were available in 2,745 men and women including 803 incident CHD cases. Geometric mean us-troponin I was 1.56 ng/L. Mean (SD) follow-up was 16.0 (5.8) years. Results: Baseline concentrations of us-troponin I were higher in cases compared to non-cases (geometric mean 2.56 vs. 1.49 ng/L, p&lt;0.0001) and in men compared to women (geometric mean 1.93 vs. 1.27 ng/L, p&lt;0.0001). After adjustment for variables of the Framingham Risk Score, the hazard ratio (HR) with 95% confidence interval (CI) for a CHD event in the top quartile compared to the bottom quartile was 2.76 (95% CI, 1.87-4.09). After additional adjustment for alcohol intake, physical activity, and body mass index, hazard ratios remained essentially unchanged. Conclusions: Troponin I measured by an us-assay was detectable in almost all subjects. This is the first population-based prospective study with long-term follow-up showing that even modestly increased concentrations of us troponin I are strongly associated with incident CHD independently of a variety of traditional risk factors.
Preclinical antitumor activity of benzopyranones
Authors: Rama Krishna Narla, Alice Collette, Bernd Stein, David Giegel, Garrick Packard, Glenn Friedman, Heather Raymon, Jim Gamez, Jonathan Wright, Kimberly Fultz, Michael Boluro-Ajayi, Michael A. Shirley, Patrick Papa, Paul Erdman, Seema Pai, Steve Sakata
Journal: Cancer Research (2005)

5891  Agents with selective estrogen receptor modulatory (SERM) activities have been widely used in the treatment and prevention of cancers such as breast cancer and endometrial carcinoma that express estrogen receptors. Furthermore, SERMs (e.g., Tamoxifen) also have been shown to have anticancer activity in cancers that do not express estrogen receptors, suggesting an estrogen receptor-independent antitumor mechanism for the agents. CC-8490 is a novel benzopyranone that has potent SERM activity in bone and breast cancer cell lines that express estrogen receptors. Recently it was discovered that CC-8490 induces apoptosis and inhibits the tumor growth of U87 glioblastoma tumors implanted subcutaneously and prolonged the survival of mice with intracranial glioblastoma. CC-8490 is currently in a Phase I dose escalation study in patients with glioblastoma. In the current preclinical study we evaluated the anticancer activity of CC-8490 and its analogs in various tumor types. CC-8490 and its close analogs were tested in a panel of 15 cancer cell lines representing 9 different tumor types including glioblastoma, leukemia, breast, colon, prostate, pancreatic ovarian, non-small cell and uterine cancers. The compounds inhibited the proliferation of these cancer cells lines and also a multi-drug resistant phenotype (MES-SA-dx5) of a uterine carcinoma cell line (MES-SA) with IC50 values in low micromolar range. CC-8490 and its analogs were also tested in a panel of SCID mouse xenograft models of human cancer cell lines including glioblastoma, non-small cell lung cancer (NSCLC), colon and breast cancers. Once daily intraperitonial administration of CC-8490 and its analog Cpd-A to SCID mice with established U87 glioblastoma tumors at 30 and 50 mg/kg resulted in dose-dependent inhibition of tumor growth with TGD (tumor growth delay) of 2 and 5 days (for CC-8490) and 3 and 7 days (for Cpd-A), respectively. The %T/C ratios on day 38 for CC-8490 were 55 and 35 for 30 and 50 mg/kg, respectively. The %T/C values for Cpd-A on day 39 were 35 and 23 at 30 and 50 mg/kg, respectively. In NCI-H460 (NSCLC) xenograft model, a 30 mg/kg (qd) dose of CC-8490 and its analogs Cpd-A, Cpd-B and Cpd-C inhibited the tumor growth with %T/C ratios of 46, 49, 51 and 53 on day 28, respectively. This inhibition was similar to that of a maximum tolerated dose of 10 mg/kg Docetaxel administered at q4d (i.v.). These compounds were well tolerated as measured by loss of body weights. Tumor growth inhibition with CC-8490 and its analogs in HT-29 (colon cancer) and MDA-MB-231 (breast cancer) xenograft models, their histological and immunohistochemical effects will be presented. In summary, these studies demonstrate that CC-8490 and its close analogs have potent in vitro and in vivo anticancer activity against a variety of human cancer models.
Abstract 18444: Effects of Cardiac Resynchronization Therapy on Transcardiac Metabolomic Profile and Substrate Utilization
Authors: Petras Dzeja, Emirhan Nemutlu, Yi-Zhou Xu, Song Zhang, Andre Terzic, Yong-Mei Cha
Journal: Circulation (2011)

Introduction: Cardiac remodeling in heart failure (HF) is associated with conduction abnormalities and dyssynchrony which results in poorly coordinated contractions precipitating metabolic heterogeneity and energetic inefficiency. Cardiac resynchronization therapy (CRT) improves HF symptoms, ventricular function and overall survival. The aim of this study was to determine the changes in metabolomic profiles and substrate utilization after CRT. Methods: 18 patients with advanced HF and 7 healthy controls were included in this study. Blood samples were collected from peripheral vein, femoral artery (FA) and coronary sinus (CS) before and 10-min after CRT. Metabolomic profiling of plasma samples were performed using GC/MS and 1 H NMR spectroscopy. Partial Least Squares Discriminant Analysis (PLS-DA) score plots and regression coefficients were used to examine metabolomic profiles. Results: HF patients have altered plasma metabolomic profile (Fig. A) with distinct panel of metabolites including free fatty acids (FFA), glycerol, 2-hydroxybutyrate, glycine, succinate and uric acid important in group classification compared to controls. Increased release of fumarate and glycerol-3-phosphate from myocardium in HF indicate mitochondrial and substrate shuttle dysfunction. Immediately after CRT, transcardiac metabolomic profile of plasma from CS shifted to a different state with increased myocardial uptake and metabolism of FFA and decreased release of creatinine indicating improved energetic conditions (Fig. B). Conclusion: Metabolomic profiling indicates that CRT improves myocardial substrate metabolism and utilization in patients with advanced HF.
Abstract 3797: Efficacy and pharmacokinetics of gold nanorods coupled with laser-induced photoplasmonic therapy in solid tumor bearing mice
Authors: Ahmed M. Al-Abd, Ali A. Shabaka, Osama A. El-Shabrawy, Nemat A. Yassin, Sawsan S. Mahmoud, Siham M. El-Shenawy, Emad Al-Ashqar, Wael H. Eisa, Niveen M. Farag, Marwa A. El-Shaer, Nabila Salah, Mostafa A. El-Sayed
Journal: Cancer Research (2014)

Abstract Gold nanorods (GNR) are characterized by absorbing near IR beams and emitting heat which is called photoplasmonic response. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we assessed the intratumoral and tissue distribution of PEGylated GNRs as well as its antitumor efficacy (coupled with laser photoplasmonic sessions) when given intravenously or intratumoral to solid tumor bearing mice. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 and showed strong surface plasmon absorption at wave length 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic circulating time (less than 3 h). On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment. Citation Format: Ahmed M. Al-Abd, Ali A. Shabaka, Osama A. El-Shabrawy, Nemat A. Yassin, Sawsan S. Mahmoud, Siham M. El-Shenawy, Emad Al-Ashqar, Wael H. Eisa, Niveen M. Farag, Marwa A. El-Shaer, Nabila Salah, Mostafa A. El-Sayed. Efficacy and pharmacokinetics of gold nanorods coupled with laser-induced photoplasmonic therapy in solid tumor bearing mice. [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 3797. doi:10.1158/1538-7445.AM2014-3797
Foodborne Pathogens: An Illustrated Text
Authors: A. H. Varnam, M. G. Evans
Journal: Annals of Internal Medicine (1992)

Preface Acknowledgements 1. Food Poisoning: Medical And Microbiological Overview. 2. Food Poisoning: Economic, Social And Personal Aspects. 3. Foodborne Pathogenic Micro-Organisms: A Perspective. 4. Salmonella5. Shigella6. Escherichia Coli7. Yersinia8. Vibrio9. Aeromonas10. Plesiomonas Shigelloides11. Campylobacter12. Staphylococcus Aureus13. Bacillus14. Clostridium Botulinum15. Clostrdium Perfingens16. Listeria Monocytogenes17. Other Bacterial Agents Of Foodborne Disease18. Foodborne Viral Infection19. Protozoa20. Control Of Pathogenic Mocro-Organism In Food: Management Aspects21. Control Of Pahtogenic Mocro-Orgnaisms In Meat. 22. Control Of Pathogenic Micro-Organisms In Milk. 23. Control Of Organisms In Eggs. 24. Control Of Pathogenic Micro-Organisms In Fish And Shellfish. 25. Control Of Pathogenic Micro-Organisms In Miscellaneous Foods And Processes. References Further Reading Index
TNF-related apoptosis-inducing ligand (TRAIL) as a negative regulator of normal human erythropoiesis
Authors: Loris Zamai, Paola Secchiero, Sabina Pierpaoli, Alessandra Bassini, Stefano Papa, Emad S. Alnemri, Lia Guidotti, Marco Vitale, Giorgio Zauli
Journal: Blood (2000)
The ethics of hepatitis C “treatment as prevention” among prisoners
Authors: Michael H. Levy, Sarah Larney
Journal: Hepatology (2014)

Sarah Larney is supported by a National Health and Medical Research Council Early Career Fellowship (APP1035149). Potential conflict of interest: Nothing to report. To the Editor: Hepatitis C virus (HCV) infection is highly prevalent among prisoners.1 The development of new therapeutics for HCV infection has given rise to recommendations (including by one of us, S.L.) that opt‐out HCV testing be implemented in correctional settings,2 with infected individuals linked to treatment. Increasing testing and treatment of HCV infection in prisons is in line with the paradigm of “treatment as prevention”: that by reducing the pool of prevalent HCV infection through treatment, onward transmission will cease.4 There are two important issues to consider in discussions of HCV treatment as prevention in the prison context. First, prisoners are in unequal power relationships with custodial and health staff. How can we be sure that consent for HCV testing in an opt‐out environment is truly voluntary and free from coercion? Requiring prisoners to choose to not opt‐out of an HCV test, and opt‐in to an HCV test, may be an effective approach to ensuring voluntariness that also maximizes testing uptake. Furthermore, ensuring that the responsible staff do an adequate job of pretest counseling in an opt‐in setting may be a more ethical approach to increasing testing uptake than imposing a policy of opt‐out testing. Second, an important aspect of “treatment as prevention” is the converse: “prevention as treatment,” or the prevention of reinfection of treated individuals. In community settings, people successfully treated for HCV infection can usually obtain treatment for substance use disorders, including opioid substitution therapy, to assist in reducing or ceasing injecting drug use, or can access sterile needles and syringes if they do inject. Implementation of these interventions and other harm reduction measures is poor in prisons. The limited options for prisoners wishing to protect themselves against reinfection pose a significant challenge to the success of HCV “treatment as prevention” in prison settings.5 Anecdotally, prisoners are choosing to defer treatment entry in the absence of the ability to protect themselves from reinfection.