tbuckley/cabot-search huggingface dataset:
In Vitro Cultivation of Human Tumors: Establishment of Cell Lines Derived From a Series of Solid Tumors2
Authors: Donald J. Giard, Stuart A. Aaronson, George J. Todaro, Paul Arnstein, John H. Kersey, Harvey Dosik, Wade P. Parks
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article In Vitro Cultivation of Human Tumors: Establishment of Cell Lines Derived From a Series of Solid Tumors Get access Donald J. Giard, Donald J. Giard 3Meloy Laboratories, Inc., 6715 Electronic Drive, Springfield, Va. 22151 Search for other works by this author on: Oxford Academic PubMed Google Scholar Stuart A. Aaronson, Stuart A. Aaronson 4Viral Carcinogenesis Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar George J. Todaro, George J. Todaro 5Viral Leukemia and Lymphoma Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul Arnstein, Paul Arnstein 6State of California, Department of Public Health, 2151 Berkeley Way, Berkeley, Calif. 94704 Search for other works by this author on: Oxford Academic PubMed Google Scholar John H. Kersey, John H. Kersey 7Department of Pathology and Pediatrics, University of Minnesota Medical School, Minneapolis, Minn. 55455 Search for other works by this author on: Oxford Academic PubMed Google Scholar Harvey Dosik, Harvey Dosik 8Division of Hematology, Jewish Hospital and Medical Center of Brooklyn, 555 Prospect Place, Brooklyn, N.Y. 11238 Search for other works by this author on: Oxford Academic PubMed Google Scholar Wade P. Parks Wade P. Parks 4Viral Carcinogenesis Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 5, November 1973, Pages 1417–1423, https://doi.org/10.1093/jnci/51.5.1417 Published: 01 November 1973 Article history Received: 31 January 1973 Accepted: 25 July 1973 Published: 01 November 1973
Metabolic Effects of Ethanol on the Rabbit Heart
Authors: T. KIKUCHI, K. J. KAKO
Journal: Circulation Research (1970)

Ethanol in saline solution (15%, v/v) was infused into anesthetized rabbits at a rate of 0.494 ml/min for the first 12 minutes and then at 0.247 ml/min for 108 minutes. Three hours after the infusion, heart triglyceride and lipoprotein lipase were assayed. Oxidation and esterification of fatty acids (palmitate -14 C as an indicator) were assessed by using either tissue homogenates or perfused hearts taken from the rabbits. Oxidation-reduction states of the perfused hearts were examined by measuring the tissue levels of dehydrogenase-linked substrates. The infusion of ethanol resulted in 180% increase in heart triglyceride content, but the infusion of norepinephrine (3 µg/kg/min) did not change the content. No change in plasma free fatty acids and triglyceride or heart lipoprotein lipase activity was detected. Addition of ethanol had little effect on the distribution of palmitate -14 C in the lipids of tissue slices and homogenates. On the other hand, prior infusion of ethanol resulted in depression of 14 CO 2 production (70 and 50%) and enhanced fatty acid esterification into triglyceride (270 and 170%) both in homogenates and perfused hearts. Mitochondrial and cytoplasmic redox states were shifted to more oxidized states by ethanol infusion. It is postulated from these results that an accumulation of triglyceride in the rabbit heart in response to ethanol administration is a result of decreased fatty acid oxidation rather than of increased triglyceride uptake or increased fatty acid synthesis.
HOW WELL DO SEMIQUANTITATIVE PARAMETERS, INCLUDING ENDDIASTOLIC FLOW REVERSAL IN THE DESCENDING AORTA, HELP TO ASSESS AORTIC REGURGITATION? A 3D-ECHOCARDIOGRAPHY AND MAGNET RESONANCE IMAGING STUDY
Authors: Carolin Sonne, Stefanie Rosner, Martin Hadamitzky
Journal: Journal of the American College of Cardiology (2014)
Antitumor Activity of NVP-BKM120—A Selective Pan Class I PI3 Kinase Inhibitor Showed Differential Forms of Cell Death Based on p53 Status of Glioma Cells
Authors: Dimpy Koul, Jun Fu, Ruijun Shen, Tiffany A. LaFortune, Shuzhen Wang, Ningyi Tiao, Yong-Wan Kim, Juinn-Lin Liu, Deepti Ramnarian, Ying Yuan, Carlos Garcia-Echevrria, Sauveur-Michel Maira, W.K. Alfred Yung
Journal: Clinical Cancer Research (2011)

The aim of this study was to show preclinical efficacy and clinical development potential of NVP-BKM120, a selective pan class I phosphatidylinositol-3 kinase (PI3K) inhibitor in human glioblastoma (GBM) cells in vitro and in vivo.The effect of NVP-BKM120 on cellular growth was assessed by CellTiter-Blue assay. Flow cytometric analyses were carried out to measure the cell-cycle, apoptosis, and mitotic index. Mitotic catastrophe was detected by immunofluorescence. The efficacy of NVP-BKM120 was tested using intracranial U87 glioma model.We tested the biologic effects of a selective PI3K inhibitor NVP-BKM120 in a set of glioma cell lines. NVP-BKM120 treatment for 72 hours resulted in a dose-dependent growth inhibition and effectively blocked the PI3K/Akt signaling cascade. Although we found no obvious relationship between the cell line's sensitivity to NVP-BKM120 and the phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) statuses, we did observe a differential sensitivity pattern with respect to p53 status, with glioma cells containing wild-type p53 more sensitive than cells with mutated or deleted p53. NVP-BKM120 showed differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death. NVP-BKM120 mediates mitotic catastrophe mainly through Aurora B kinase. Knockdown of p53 in p53 wild-type U87 glioma cells displayed microtubule misalignment, multiple centrosomes, and mitotic catastrophe cell death. Parallel to the assessment of the compound in in vitro settings, in vivo efficacy studies using an intracranial U87 tumor model showed an increased median survival from 26 days (control cohort) to 38 and 48 days (treated cohorts).Our present findings establish that NVP-BKM120 inhibits the PI3K signaling pathways, leading to different forms of cell death on the basis of p53 statuses. Further studies are warranted to determine if NVP-BKM120 has potential as a glioma treatment.
Pharmacological Inhibition of a MicroRNA Family in Nonhuman Primates by a Seed-Targeting 8-Mer AntimiR
Authors: Veerle Rottiers, Susanna Obad, Andreas Petri, Robert McGarrah, Marie W. Lindholm, Joshua C. Black, Sumita Sinha, Robin J. Goody, Matthew S. Lawrence, Andrew S. deLemos, Henrik F. Hansen, Steve Whittaker, Steve Henry, Rohn Brookes, Seyed Hani Najafi-Shoushtari, Raymond T. Chung, Johnathan R. Whetstine, Robert E. Gerszten, Sakari Kauppinen, Anders M. Näär
Journal: Science Translational Medicine (2013)

Long-term treatment of obese, insulin-resistant nonhuman primates with a seed-targeting antimiR oligonucleotide against the microRNA-33 family derepresses hepatic expression of miR-33 targets, increases circulating HDL cholesterol, and has a clean safety profile.
Acute lung injury as a possible adverse drug reaction related to gefitinib
Authors: R. Ieki, E. Saitoh, M. Shibuya
Journal: European Respiratory Journal (2002)

Gefitinib is a potent drug used in the treatment of nonsmall-cell lung cancer (NSCLC). Gefitinib acts by inhibition of the epidermal growth factor receptor tyrosine kinase. Clinical trials have confirmed the efficacy of gefitinib for NSCLC. Adverse drug reactions, although frequent, are mild, and include acne-like skin rash and diarrhoea. The present study describes the case of a 56-yr-old male with NSCLC who, 4 weeks after treatment with gefitinib, suffered from a severe alveolar haemorrhage diagnosed by bronchoalveolar lavage. This is the first case report of an acute life-threatening lung injury in a patient with nonsmall-cell lung cancer who had been given gefitinib.
The multidrug-resistant PMEN1 pneumococcus is a paradigm for genetic success
Authors: Kelly L Wyres, Lotte M Lambertsen, Nicholas J Croucher, Lesley McGee, Anne von Gottberg, Josefina Liñares, Michael R Jacobs, Karl G Kristinsson, Bernard W Beall, Keith P Klugman, Julian Parkhill, Regine Hakenbeck, Stephen D Bentley, Angela B Brueggemann
Journal: Genome biology (2012)

Abstract Background Streptococcus pneumoniae , also called the pneumococcus, is a major bacterial pathogen. Since its introduction in the 1940s, penicillin has been the primary treatment for pneumococcal diseases. Penicillin resistance rapidly increased among pneumococci over the past 30 years, and one particular multidrug-resistant clone, PMEN1, became highly prevalent globally. We studied a collection of 426 pneumococci isolated between 1937 and 2007 to better understand the evolution of penicillin resistance within this species. Results We discovered that one of the earliest known penicillin-nonsusceptible pneumococci, recovered in 1967 from Australia, was the likely ancestor of PMEN1, since approximately 95% of coding sequences identified within its genome were highly similar to those of PMEN1. The regions of the PMEN1 genome that differed from the ancestor contained genes associated with antibiotic resistance, transmission and virulence. We also revealed that PMEN1 was uniquely promiscuous with its DNA, donating penicillin-resistance genes and sometimes many other genes associated with antibiotic resistance, virulence and cell adherence to many genotypically diverse pneumococci. In particular, we describe two strains in which up to 10% of the PMEN1 genome was acquired in multiple fragments, some as long as 32 kb, distributed around the recipient genomes. This type of directional genetic promiscuity from a single clone to numerous unrelated clones has, to our knowledge, never before been described. Conclusions These findings suggest that PMEN1 is a paradigm of genetic success both through its epidemiology and promiscuity. These findings also challenge the existing views about horizontal gene transfer among pneumococci.
Delaying the International Spread of Pandemic Influenza
Authors: Ben S Cooper, Richard J Pitman, W. John Edmunds, Nigel J Gay
Journal: PLoS Medicine (2006)

Background The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. Methods and Findings To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. Conclusions Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.
ABCG2 Harboring the Gly482 Mutation Confers High-Level Resistance to Various Hydrophilic Antifolates
Authors: Assaf Shafran, Ilan Ifergan, Eran Bram, Gerrit Jansen, Ietje Kathmann, Godefridus J. Peters, Robert W. Robey, Susan E. Bates, Yehuda G. Assaraf
Journal: Cancer Research (2005)

Abstract ABCG2 is an ATP-binding cassette transporter that confers resistance to various chemotherapeutic agents. Recent studies have established that an Arg (wild-type) to Gly mutation at amino acid 482 in ABCG2 alters substrate specificity. Here, we explored the role of this G482 mutation in antifolate resistance using a clinically relevant 4-hour drug exposure. Stable transfectants overexpressing the mutant G482 transporter displayed 120-, 1,000-, and &amp;gt;6,250-fold resistance to the antifolates methotrexate, GW1843, and Tomudex, respectively, relative to parental human embryonic kidney cells. Moreover, although overexpressing equal transporter levels at the plasma membrane, G482-ABCG2 cells were 6-, 23-, and &amp;gt;521-fold more resistant to methotrexate, GW1843, and Tomudex, respectively, than R482-ABCG2 cells. In contrast, upon a continuous (72-hour) drug exposure, both the G482- and R482-ABCG2 cells lost almost all their antifolate resistance; this result was consistent with the inability of ABCG2 to extrude long-chain antifolate polyglutamates. Ko143, a specific and potent ABCG2 inhibitor reversed methotrexate resistance in both G482- and R482-ABCG2 cells. Consistently, whereas the pool of free methotrexate in parental human embryonic kidney cells was prominent after 4 hours of transport with 1 μmol/L [3H]methotrexate, in R482- and G482-ABCG2 cells, it was minimal. Furthermore, G482-ABCG2 cells contained marked decreases in the di- and triglutamate species of [3H]methotrexate at 4 hours of incubation with methotrexate and in the tetra- and pentaglutamates at 24 hours. These changes were not associated with any significant decrease in folylypoly-γ-glutamate synthetase activity. These results provide the first evidence that the G482-ABCG2 mutation confers high-level resistance to various hydrophilic antifolates.
Direct Marketing of Pharmaceuticals to Consumers
Authors: Alan Lyles
Journal: Annual Review of Public Health (2002)

▪ Abstract Revised FDA regulations governing pharmaceutical companies' broadcast advertisements directed to consumers produced substantial increases in direct-to-consumer advertising (DTCA) expenditures. Proponents of DTCA claim it supports patient autonomy in the patient-physician relationship and has motivated some consumers to seek a physician's care for conditions they previously had not discussed with a doctor. However, DTCA's blend of promotion and information has produced more prescription drug awareness than knowledge—it has been largely ineffective in educating patients with medical conditions about the medications for those conditions. The evidence for DTCA's increase in pharmaceutical sales is as impressive as is the lack of evidence concerning its impact on the health of the public. Broadcast advertisements are too brief to include extensive technical information; consequently, the impact of FDA regulations to assure a fair balance of risk and benefit in DTCA is still being assessed.
Diagnosis of Comorbid Psychiatric Disorders in Substance Users Assessed With the Psychiatric Research Interview for Substance and Mental Disorders for DSM-IV
Authors: Deborah Hasin, Sharon Samet, Edward Nunes, Jakob Meydan, Karen Matseoane, Rachel Waxman
Journal: American Journal of Psychiatry (2006)

Objective: The authors used the Psychiatric Research Interview for Substance and Mental Disorders for DSM-IV (PRISM-IV) to test the reliability of DSM-IV-defined disorders, including primary and substance-induced disorders, in substance-abusing subjects. Method: Substance-abusing patients (N=285) from substance abuse/dual-diagnosis treatment settings and mental health treatment settings participated in test and blind retest interviews with the PRISM-IV, which includes specific guidelines for assessment of substance abusers. Results: Kappas for primary and substance-induced major depressive disorder ranged from 0.66 to 0.75. Reliability for psychotic disorders, eating disorders, antisocial personality disorder, and borderline personality disorder was in the same range. Reliability for most anxiety disorders was lower. Reliability was good to excellent (kappas ≥0.65) for most substance dependence disorders. Continuous measures (severity, age at onset) had intraclass correlation coefficients >0.70 with few exceptions. Reliability was better for primary than for substance-induced disorders, although not greatly so. Conclusion: Most DSM-IV psychiatric disorders can be assessed in substance-abusing subjects with acceptable to excellent reliability by using specifically designed procedures. Good reliability improves the likelihood of significant study results.
Time constant/volume relationship of passive expiration in mechanically ventilated ARDS patients
Authors: J Guttmann, L Eberhard, B Fabry, W Bertschmann, J Zeravik, M Adolph, J Eckart, G Wolff
Journal: European Respiratory Journal (1995)

Since the adult respiratory distress syndrome (ARDS) lung is known to be inhomogeneous, one could expect an uneven distribution of expiratory time constant during uninterrupted mechanical ventilation. We investigated the time constant/volume relationship of passive expiration, and their modification by external resistive elements. In 12 paralysed intubated ARDS patients, we determined the expiratory time constant (tau E) as a function of the expired volume (VE) during uninterrupted mechanical ventilation. Mean expiratory time was 2.9 +/- 0.3 s (+/- SD). VE was divided into five equal volume slices (portions) and a mean tau E calculated from the expiratory tidal volume/flow curve for each slice. The mean values of tau E for each volume slice did not differ significantly throughout expiration, averaging 690 +/- 218 ms (mean +/- SD of five slices and 12 patients). We show that the flow-dependent resistance of the endotracheal tube (RETT) is mainly responsible for the observed time constant homogeneity. We conclude that in ARDS patients during uninterrupted mechanical ventilation the time constants of passive expiration are markedly modified by the flow-dependent resistance of the endotracheal tube (RETT), and also by the external resistance of tubing and ventilator (REX). RETT and REX render tau E about three times larger than the time constant of the patient's respiratory system alone.
A 5-MicroRNA Signature for Lung Squamous Cell Carcinoma Diagnosis and hsa-miR-31 for Prognosis
Authors: Xiaogang Tan, Wenyan Qin, Liang Zhang, Jie Hang, Baozhong Li, Cuiyan Zhang, Junting Wan, Fang Zhou, Kang Shao, Yimin Sun, Jianping Wu, Xun Zhang, Bin Qiu, Ning Li, Susheng Shi, Xiaoli Feng, Shouhua Zhao, Zhen Wang, Xiaohong Zhao, Zhaoli Chen, Keith Mitchelson, Jing Cheng, Yong Guo, Jie He
Journal: Clinical Cancer Research (2011)

Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients.MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I-III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined.We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan-Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan-Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2.Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31.
Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study
Authors: Kiyoshi Asada, Takeshi Nakajima, Taichi Shimazu, Nobutake Yamamichi, Takao Maekita, Chizu Yokoi, Ichiro Oda, Takayuki Ando, Takeichi Yoshida, Sohachi Nanjo, Mitsuhiro Fujishiro, Takuji Gotoda, Masao Ichinose, Toshikazu Ushijima
Journal: Gut (2014)

<h3>Background</h3> Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation. <h3>Objective</h3> To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels. <h3>Design</h3> Patients with early gastric cancer, aged 40–80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after <i>Helicobacter pylori</i> infection discontinued. Methylation levels of three preselected genes (<i>miR-124a-3</i>, <i>EMX1</i> and <i>NKX6-1</i>) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment. <h3>Results</h3> Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1–2, 2–3 and ≥3 years after the enrolment, respectively. The highest quartile of the <i>miR-124a-3</i> methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for <i>EMX1</i> and <i>NKX6-1</i>. <h3>Conclusions</h3> Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.