tbuckley/cabot-search huggingface dataset:
Development of a Rapid Chemosensitivity Test for Anticancer Drugs With Contact-Sensitive Monolayer of Balb/3T3 Cells
Authors: M Nakayama, S Nakano, T Koga, Y Niho
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Development of a Rapid Chemosensitivity Test for Anticancer Drugs With Contact-Sensitive Monolayer of Balb/3T3 Cells Get access Masaaki Nakayama, Masaaki Nakayama Search for other works by this author on: Oxford Academic PubMed Google Scholar Shuji Nakano, Shuji Nakano * *Correspondence to. Dr Shuji Nakano, First Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Fukuoka 812, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Tatsuhiko Koga, Tatsuhiko Koga Search for other works by this author on: Oxford Academic PubMed Google Scholar Yoshiyuki Niho Yoshiyuki Niho Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 2, 18 January 1989, Pages 153–157, https://doi.org/10.1093/jnci/81.2.153 Published: 18 January 1989 Article history Received: 26 January 1988 Revision received: 01 September 1988 Accepted: 09 September 1988 Published: 18 January 1989
Quinine protects pyruvate‐kinase deficient red cells from dehydration
Authors: Charles A. Koller, Eugene P. Orringer, John C. Parker
Journal: American Journal of Hematology (1979)

Abstract Pyruvate kinase deficient red blood cells have an abnormal tendency to lose ATP when exposed to low pO 2 or cyanide, whereas normal red cells do not. Once energy is depleted, all red cells take up calcium and subsequently lose intracellular potassium and water. It has been shown previously that quinine will inhibit the potassium and water flux seen in energy depleted normal cells. The present study indicates that quinine protects cyanide treated pyruvate kinase deficient erythrocytes from water and potassium loss. Quinine does not prevent ATP depletion or calcium uptake. By six hours, cyanide treated pyruvate kinase deficient cells have lost an average of 486 gm of water per kilogram cell solids and 140 mmoles of potassium per kilogram of cell solids, while cells treated with both quinine and cyanide have lost only 106 gm of water per kilogram of cell solids and 77 mmoles of potassium per kilogram of cell solids. These data support the concept that the membrane lesion in pyruvate kinase deficiency is secondary to ATP depletion and is a manifestation of the Gardos effect. Quinine may have therapeutic potential in the treatment of pyruvate kinase deficiency hemolytic anemia.
Flexible Programs of Chemokine Receptor Expression on Human Polarized T Helper 1 and 2 Lymphocytes
Authors: Federica Sallusto, Danielle Lenig, Charles R. Mackay, Antonio Lanzavecchia
Journal: The Journal of Experimental Medicine (1998)

Chemokines and their receptors are important elements for the selective attraction of various subsets of leukocytes. To better understand the selective migration of functional subsets of T cells, chemokine receptor expression was analyzed using monoclonal antibodies, RNase protection assays, and the response to distinct chemokines. Naive T cells expressed only CXC chemokine receptor (CXCR)4, whereas the majority of memory/activated T cells expressed CXCR3, and a small proportion expressed CC chemokine receptor (CCR)3 and CCR5. When polarized T cell lines were analyzed, CXCR3 was found to be expressed at high levels on T helper cell (Th)0s and Th1s and at low levels on Th2s. In contrast, CCR3 and CCR4 were found on Th2s. This was confirmed by functional responses: only Th2s responded with an increase in [Ca2+]i to the CCR3 and CCR4 agonists eotaxin and thymus and activation regulated chemokine (TARC), whereas only Th0s and Th1s responded to low concentrations of the CXCR3 agonists IFN-γ–inducible protein 10 (IP-10) and monokine induced by IFN-γ (Mig). Although CCR5 was expressed on both Th1 and Th2 lines, it was absent in several Th2 clones and its expression was markedly influenced by interleukin 2. Chemokine receptor expression and association with Th1 and Th2 phenotypes was affected by other cytokines present during polarization. Transforming growth factor β inhibited CCR3, but enhanced CCR4 and CCR7 expression, whereas interferon α inhibited CCR3 but upregulated CXCR3 and CCR1. These results demonstrate that chemokine receptors are markers of naive and polarized T cell subsets and suggest that flexible programs of chemokine receptor gene expression may control tissue-specific migration of effector T cells.
Nonuniform epicardial activation and repolarization properties of in vivo canine pulmonary conus.
Authors: M J Burgess, B M Steinhaus, K W Spitzer, P R Ershler
Journal: Circulation Research (1988)

The relation between nonuniform epicardial activation and ventricular repolarization properties was studied in 14 pentobarbital anesthetized dogs and with a computer model. In 11 dogs, isochrone maps of epicardial activation sequence were constructed from electrograms recorded from the pulmonary conus with 64 electrodes on an 8 X 8 grid with 2-mm electrode separation. The heart was paced from multiple sites on the periphery of the array. Uniformity of epicardial activation was estimated from activation times at test sites and their eight neighboring sites. Acceleration shortened and deceleration prolonged refractory periods. The locations of acceleration and deceleration sites of activation differed during drives from various sites, and differences in uniformity of activation during pairs of drives were correlated to differences in refractory periods (r = 0.76, range 0.59-0.93). In three additional experiments, transmural activation sequence maps were constructed from electrograms recorded from needle-mounted electrodes placed upstream and downstream to epicardial activation delays. Activation proceeded from epicardium to endocardium upstream to the delays and from endocardium to epicardium downstream to the delays. A computer simulation of two-dimensional action potential propagation based on the Beeler-Reuter myocardial membrane model provided insights to the mechanism for the results of the animal experiments. The two-dimensional sheet modeled the transmural anisotropic histology of the canine pulmonary conus and corresponded to previous reports and histology of specimens from five experiments. Simulated activation patterns were similar to those found in the experimental animals. In addition, action potentials were electronically prolonged at sites of deceleration and shortened at sites of acceleration, results comparable to the animal experiments. Our findings demonstrate that the location of areas of nonuniform epicardial activation is dependent on drive site and that nonuniform activation electronically modulates repolarization properties. Therefore it seems likely that the site of origin of ectopic ventricular complexes, especially in ischemic myocardium where activation is nonuniform, could be an important determinant of whether ectopic activity initiates sustained tachyarrhythmias.
2-weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial
Authors: Pirkko-Liisa Kellokumpu-Lehtinen, Ulrika Harmenberg, Timo Joensuu, Ray McDermott, Petteri Hervonen, Claes Ginman, Marjaana Luukkaa, Paul Nyandoto, Akseli Hemminki, Sten Nilsson, John McCaffrey, Raija Asola, Taina Turpeenniemi-Hujanen, Fredrik Laestadius, Tiina Tasmuth, Katinka Sandberg, Maccon Keane, Ilari Lehtinen, Tiina Luukkaala, Heikki Joensuu
Journal: The Lancet Oncology (2013)
Pivotal Roles of Snail Inhibition and RKIP Induction by the Proteasome Inhibitor NPI-0052 in Tumor Cell Chemoimmunosensitization
Authors: Stavroula Baritaki, Kam Yeung, Michael Palladino, James Berenson, Benjamin Bonavida
Journal: Cancer Research (2009)

Abstract The novel proteasome inhibitor NPI-0052 has been shown to sensitize tumor cells to apoptosis by various chemotherapeutic drugs and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), although the mechanisms involved are not clear. We hypothesized that NPI-0052–mediated sensitization may result from NF-κB inhibition and downstream modulation of the metastasis inducer Snail and the metastasis suppressor/immunosurveillance cancer gene product Raf-1 kinase inhibitory protein (RKIP). Human prostate cancer cell lines were used as models, as they express different levels of these proteins. We show that NPI-0052 inhibits both NF-κB and Snail and induces RKIP expression, thus resulting in cell sensitization to CDDP and TRAIL. The direct role of NF-κB inhibition in sensitization was corroborated with the NF-κB inhibitor DHMEQ, which mimicked NPI-0052 in sensitization and inhibition of Snail and induction of RKIP. The direct role of Snail inhibition by NPI-0052 in sensitization was shown with Snail small interfering RNA, which reversed resistance and induced RKIP. Likewise, the direct role of RKIP induction in sensitization was revealed by both overexpression of RKIP (mimicking NPI-0052) and RKIP small interfering RNA that inhibited NPI-0052–mediated sensitization. These findings show that NPI-0052 modifies the NF-κB-Snail-RKIP circuitry in tumor cells and results in downstream inhibition of antiapoptotic gene products and chemoimmunosensitization. The findings also identified Snail and RKIP as targets for reversal of resistance. [Cancer Res 2009;69(21):8376–85]
Clinical Validation of Colorectal Cancer Biomarkers Identified from Bioinformatics Analysis of Public Expression Data
Authors: Yeonjoo Jung, Sanghyuk Lee, Hyung-Seok Choi, Soon-Nam Kim, Eunyoung Lee, Youngah Shin, Jihae Seo, Bumjin Kim, Yeonhwa Jung, Wan Kyu Kim, Ho-Kyung Chun, Woo Yong Lee, Jaesang Kim
Journal: Clinical Cancer Research (2011)

Identification of novel biomarkers of cancer is important for improved diagnosis, prognosis, and therapeutic intervention. This study aimed to identify marker genes of colorectal cancer (CRC) by combining bioinformatics analysis of gene expression data and validation experiments using patient samples and to examine the potential connection between validated markers and the established oncogenes such as c-Myc and K-ras.Publicly available data from GenBank and Oncomine were meta-analyzed leading to 34 candidate marker genes of CRC. Multiple case-matched normal and tumor tissues were examined by RT-PCR for differential expression, and 9 genes were validated as CRC biomarkers. Statistical analyses for correlation with major clinical parameters were carried out, and RNA interference was used to examine connection with major oncogenes.We show with high confidence that 9 (ECT2, ETV4, DDX21, RAN, S100A11, RPS4X, HSPD1, CKS2, and C9orf140) of the 34 candidate genes are expressed at significantly elevated levels in CRC tissues compared to normal tissues. Furthermore, high-level expression of RPS4X was associated with nonmucinous cancer cell type and that of ECT2 with lack of lymphatic invasion while upregulation of CKS2 was correlated with early tumor stage and lack of family history of CRC. We also demonstrate that RPS4X and DDX21 are regulatory targets of c-Myc and ETV4 is downstream to K-ras signaling.We have identified multiple novel biomarkers of CRC. Further analyses of their function and connection to signaling pathways may reveal potential value of these biomarkers in diagnosis, prognosis, and treatment of CRC.
Cumulative Community-Level Lead Exposure and Pulse Pressure: The Normative Aging Study
Authors: Todd Perlstein, Jennifer Weuve, Joel Schwartz, David Sparrow, Robert Wright, Augusto Litonjua, Huiling Nie, Howard Hu
Journal: Environmental Health Perspectives (2007)

Pulse pressure increases with age in industrialized societies as a manifestation of arterial stiffening. Lead accumulates in the vasculature and is associated with vascular oxidative stress, which can promote functional and structural vascular disease.We tested the hypothesis that cumulative community-level lead exposure, measured with K-X-ray fluorescence, is associated with pulse pressure in a cohort of adult men.In a cross-sectional analysis of 593 men not treated with antihypertensive medication, tibia lead was positively associated with pulse pressure (p < 0.001). Adjusting for age, race, diabetes, family history of hypertension, education, waist circumference, alcohol intake, smoking history, height, heart rate, fasting glucose, and total cholesterol-to-HDL ratio, increasing quintiles of tibia lead remained associated with increased pulse pressure (ptrend = 0.02). Men with tibia lead above the median (19.0 microg/g) had, on average, a 4.2-mmHg (95% confidence interval, 1.9-6.5) higher pulse pressure than men with tibia lead level below the median. In contrast, blood lead level was not associated with pulse pressure.These data indicate that lead exposure may contribute to the observed increase in pulse pressure that occurs with aging in industrialized societies. Lead accumulation may contribute to arterial aging, perhaps providing mechanistic insight into the observed association of low-level lead exposure with cardiovascular mortality.
Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis
Authors: Nora Anderson, Jürgen Borlak
Journal: Pharmacological Reviews (2008)

Steatosis of the liver may arise from a variety of conditions, but the molecular basis for lipid droplet formation is poorly understood. Although a certain amount of lipid storage may even be hepatoprotective, prolonged lipid storage can result in an activation of inflammatory reactions and loss of metabolic competency. Apart from drug-induced steatosis, certain metabolic disorders associated with obesity, insulin resistance, and hyperlipidemia give also rise to nonalcoholic fatty liver diseases (NAFLD). It is noteworthy that advanced stages of nonalcoholic hepatic steatosis and steatohepatitis (NASH) result ultimately in fibrosis and cirrhosis. In this regard, the lipid droplets (LDs) have been discovered to be metabolically highly active structures that play major roles in lipid transport, sorting, and signaling cascades. In particular, LDs maintain a dynamic communication with the endoplasmic reticulum (ER) and the plasma membrane via sphingolipid-enriched domains of the plasma membrane—the lipid rafts. These microdomains frequently harbor receptor tyrosine kinases and other signaling molecules and connect extracellular events with intracellular signaling cascades. Here, we review recent knowledge on the molecular mechanisms of drug and metabolically induced hepatic steatosis and its progression to steatohepatitis (NASH). The contribution of cytokines and other signaling molecules, as well as activity of nuclear receptors, lipids, transcription factors, and endocrine mediators toward cellular dysfunction and progression of steatotic liver disease to NASH is specifically addressed, as is the cross-talk of different cell types in the pathogenesis of NAFLD. Furthermore, we provide an overview of recent therapeutic approaches in NASH therapy and discuss new as well as putative targets for pharmacological interventions.
Single-Agent Versus Combination Chemotherapy in Advanced Non–Small-Cell Lung Cancer: The Cancer and Leukemia Group B (study 9730)
Authors: Rogerio C. Lilenbaum, James E. Herndon, Marcy A. List, Chris Desch, Dorothy M. Watson, Antonius A. Miller, Stephen L. Graziano, Michael C. Perry, Wayne Saville, Philippe Chahinian, Jane C. Weeks, Jimmie C. Holland, Mark R. Green
Journal: Journal of Clinical Oncology (2004)

We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer.A total of 561 eligible patients were randomly assigned to receive paclitaxel alone or in combination with carboplatin.The response rate was 17% in the paclitaxel arm and 30% in the carboplatin-paclitaxel arm (P < .0001). Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm (P = .0002). Median survival times were 6.7 months (95% CI, 5.8 to 7.8) and 8.8 months (95% CI, 8.0 to 9.9), and 1-year survival rates were 32% (95% CI, 27% to 38%), and 37% (95% CI, 32% to 43%), respectively. The overall survival distributions were not statistically different: hazard ratio = 0.91 (95% CI, 0.77 to 1.17; P = .25). Hematological toxicity and nausea were more frequent in the combination arm, but febrile neutropenia and toxic deaths were equally low in both arms. There was no significant survival difference in elderly patients. Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy (P = .019).Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy, but there was no statistically significant difference in the primary end point of overall survival. The results in elderly patients were similar to younger patients. Performance status 2 patients had a superior outcome when treated with combination chemotherapy.
Molecular Genetic Studies of Gene Identification for Osteoporosis: The 2009 Update
Authors: Xiang-Hong Xu, Shan-Shan Dong, Yan Guo, Tie-Lin Yang, Shu-Feng Lei, Christopher J. Papasian, Ming Zhao, Hong-Wen Deng
Journal: Endocrine Reviews (2010)

Osteoporosis is a complex human disease that results in increased susceptibility to fragility fractures. It can be phenotypically characterized using several traits, including bone mineral density, bone size, bone strength, and bone turnover markers. The identification of gene variants that contribute to osteoporosis phenotypes, or responses to therapy, can eventually help individualize the prognosis, treatment, and prevention of fractures and their adverse outcomes. Our previously published reviews have comprehensively summarized the progress of molecular genetic studies of gene identification for osteoporosis and have covered the data available to the end of September 2007. This review represents our continuing efforts to summarize the important and representative findings published between October 2007 and November 2009. The topics covered include genetic association and linkage studies in humans, transgenic and knockout mouse models, as well as gene-expression microarray and proteomics studies. Major results are tabulated for comparison and ease of reference. Comments are made on the notable findings and representative studies for their potential influence and implications on our present understanding of the genetics of osteoporosis.
Biased DNA Segregation and Cardiac Stem Cell Therapies
Authors: Richard P. Harvey, Shahragim Tajbakhsh
Journal: Circulation Research (2012)

I schemic heart disease is one of our greatest killers and the epidemic of heart failure in Western countries is now being replicated in developing nations.In the headlong search for new therapies that will stimulate replacement of cardiomyocytes and vasculature lost to injury, great hope is being placed on stem cell and regeneration therapies.In this edition of the Circulation Research, Kajstura and colleagues 1 report that a minority of human cardiac stem cells (hCSCs), when they divide in vitro, undergo asymmetrical chromatid segregation (ACS), whereby the ancestral DNA strands of all of their chromosomes segregate to 1 of the 2 daughter cells, presumably a property of executive stem cells.Preparations of stem cells enriched in those undergoing ACS have a superior ability, when injected into the boarder zone of rats at the time of myocardial infarction, to expand, migrate into the infarct zone, preserve function, and prevent adverse remodeling.
The Effect of Early Deprivation on the Social Behavior of Adolescent Chimpanzees
Authors: CORBETT H. TURNER, RICHARD K. DAVENPORT, CHARLES M. ROGERS
Journal: American Journal of Psychiatry (1969)

Chimpanzees reared during early life in environments with social and perceptual restrictions are strikingly different from animals reared by their mothers in a natural habitat. As adolescents they avoid social contact and display little species-typical behavior; they play and copulate infrequently and do not groom. The authors found these aberrations to be very resistant to modification by a variety of maneuvers, including contact with normal social partners, drugs, and experimental manipulations, and they discuss the implications of their lack of "therapeutic" success.
Boosting pigment epithelial-derived factor: a promising approach for the treatment of early portal hypertension
Authors: Umberto Vespasiani-Gentilucci, Krista Rombouts
Journal: Gut (2014)

Portal hypertension (PHT) is a heterogeneous clinical entity which develops in patients with cirrhosis. It is responsible for many of the complications that occur in cirrhosis, including gastroesophageal varices, hepatorenal syndrome, ascites, hepatic encephalopathy and hypersplenism.1 There are three principal factors responsible for the development of PHT, namely (1) purely mechanical obstruction resulting from hepatic fibrosis and regenerative nodules; (2) contraction of sinusoidal and perisinusoidal contractile cells due to an imbalance between intrahepatic vasoconstrictory and vasodilatory mediators and (3) splanchnic vasodilation and increased portal blood flow.1 Factors leading to the development of PHT include hypoxia, oxidative stress, inflammation and shear stress as potential mediators for the angiogenic response. Vascular Endothelial Growth factor (VEGF) is a key mediator in regulating the angiogenic switch in many pathological conditions, and is also probably a major player in the neoangiogenic process during the development of a hyperdynamic splanchnic circulation, and the formation of portal-systemic collateral vessels.2 This has led to many studies seeking to identify signalling pathways that interact with, or affect the formation and action of VEGF switching.

Mejias reports in this issue3 a new mechanism and therapeutic effect by targeting endogenous pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats. PEDF belongs to the subgroup of the so-called non-inhibitory serpins that lack the protease inhibitory activity …
Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial
Authors: A Alloueche, W Bailey, S Barton, J Bwika, P Chimpeni, CO Falade, FA Fehintola, J Horton, S Jaffar, T Kanyok, PG Kremsner, JG Kublin, T Lang, MA Missinou, C Mkandala, Z Premji, L Robertson, A Sowunmi, SA Ward, PA Winstanley, A Oduola
Journal: The Lancet (2004)
Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease
Authors: Pamela S. Douglas, Udo Hoffmann, Manesh R. Patel, Daniel B. Mark, Hussein R. Al-Khalidi, Brendan Cavanaugh, Jason Cole, Rowena J. Dolor, Christopher B. Fordyce, Megan Huang, Muhammad Akram Khan, Andrzej S. Kosinski, Mitchell W. Krucoff, Vinay Malhotra, Michael H. Picard, James E. Udelson, Eric J. Velazquez, Eric Yow, Lawton S. Cooper, Kerry L. Lee
Journal: New England Journal of Medicine (2015)

Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care.