tbuckley/cabot-search huggingface dataset:
Benign Mesenchymal Stromal Cells in Human Sarcomas
Authors: Alexei Morozov, Robert J. Downey, John Healey, Andre L. Moreira, Emil Lou, Anna Franceschino, Yildirim Dogan, Roland Leung, Mark Edgar, Michael LaQuaglia, Robert G. Maki, Malcolm A.S. Moore
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Recent evidence suggests that at least some sarcomas arise through aberrant differentiation of mesenchymal stromal cells (MSCs), but MSCs have never been isolated directly from human sarcoma specimens. Experimental Design: We examined human sarcoma cell lines and primary adherent cultures derived from human sarcoma surgical samples for features of MSCs. We further characterized primary cultures as either benign or malignant by the presence of tumor-defining genetic lesions and tumor formation in immunocompromised mice. Results: We show that a dedifferentiated liposarcoma cell line DDLS8817 posesses fat, bone, and cartilage trilineage differentiation potential characteristic of MSCs. Primary sarcoma cultures have the morphology, surface immunophenotype, and differentiation potential characteristic of MSCs. Surprisingly, many of these cultures are benign, as they do not form tumors in mice and lack sarcoma-defining genetic lesions. Consistent with the recently proposed pericyte origin of MSCs in normal human tissues, sarcoma-derived benign MSCs (SDBMSCs) express markers of pericytes and cooperate with endothelial cells in tube formation assays. In human sarcoma specimens, a subset of CD146-positive microvascular pericytes expresses CD105, an MSC marker, whereas malignant cells largely do not. In an in vitro coculture model, SDBMSCs as well as normal human pericytes markedly stimulate the growth of sarcoma cell lines. Conclusions: SDBMSCs/pericytes represent a previously undescribed stromal cell type in sarcoma that may contribute to tumor formation. Clin Cancer Res; 16(23); 5630–40. ©2010 AACR.
Mechanisms of Mitogen-Activated Protein Kinase Inhibition by Parathyroid Hormone in Osteoblast-Like Cells
Authors: Meike Ho[Combining Diaeresis]mme, Claus P. Schmitt, Otto Mehls, Franz Schaefer
Journal: Journal of the American Society of Nephrology (2004)

Parathyroid hormone (PTH) dose dependently inhibits growth factor- and stress-induced osteoblast proliferation via inactivating mitogen-activated protein kinase (MAPK) signaling pathways. Osteoblasts have recently been shown to express MAPK phosphatase (MKP)-1, a dual-specific phosphatase inactivator of MAPK. Investigated was the role of MKPs in the PTH-induced attenuation of MAPK and Jun N-terminal kinase (JNK) signaling in osteoblast-like UMR106-01 cells. PTH induced a persistent inhibition of p42/44 MAPK and JNK phosphorylation starting at 10 min of incubation and lasting for at least 2 h. Actinomycin D affected both p42/44 MAPK and JNK dephosphorylation by PTH, suggesting a transcription-dependent mechanism of action. PTH rapidly and transiently induced expression of MKP-1. MKP-1 mRNA was already elevated after 10 min of 10(-7) M PTH incubation, reached maximal expression after 30 to 60 min, and remained elevated after 4 h. MKP-1 protein was also upregulated within 30 to 60 min of PTH administration. The protein kinase A inhibitor H89 partly reduced PTH-induced MKP-1 expression, but the protein kinase C inhibitor bisindolylmaleimide had no effect, suggesting that PTH induces MKP-1 mainly via the protein kinase A pathway. MKP-2 mRNA was downregulated after 2 h after an early period of induction, and MKP-3 mRNA was immediately reduced. Ro 318-220 did not affect PTH-induced MAPK inactivation but effectively blocked JNK dephosphorylation. The time course of PTH-induced MKP-1 protein expression closely correlated with JNK dephosphorylation. PTH attenuates the stress-induced JNK signaling pathway in osteoblasts via induction of MKP-1 synthesis but inhibits the p42/44 MAPK pathway mainly via transcription-independent mechanisms.
The dual route hypothesis in visual cognition: Why a developmental approach is necessary
Authors: Denis Mareschal, Jordy Kaufman
Journal: Behavioral and Brain Sciences (2002)

Norman presents intriguing arguments in support of a mapping between ecological and constructivist visual cognition, on the one hand, onto the dorsal ventral dual route processing hypothesis, on the other hand. Unfortunately, his account is incompatible with developmental data on the functional emergence of the dorsal and ventral routes. We argue that it is essential for theories of adult visual cognition to take constraints from development seriously.
Marathon medicine and introduction.
Authors: D. Tunstall Pedoe
Journal: British Journal of Sports Medicine (1984)

This edition of the BJSM is devoted to medical and physiological aspects of marathon running.Following the very successful Sports Council and Health Education Council sponsored symposium at Lilleshall on "Exercise, Health and Medicine" in May 1983 I suggested to the Fitness and Health Advisory Group of the Sports Council that a symposium on "Marathon Medicine" would be a useful sequel.As Medical Director of the London Marathon I had been bombarded with letters from doctors requiring advice on the medical aspects of marathon running and the facilities required at these events and I thought that it was an opportune time to bring a group of experts together to make recommenda- tions on race medical support and exchange information on some of the physiological and medical aspects of long distance running.This suggestion
Treatment of Nasal Inflammation Decreases the Ability of Subjects with Asthma to Condition Inspired Air
Authors: Jayant M. Pinto, Paraya Assanasen, Fuad M. Baroody, Edward Naureckas, Julian Solway, Robert M. Naclerio
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We previously showed that individuals with seasonal allergy have a reduced ability to condition air, which was improved by nasal inflammation. We also showed that subjects with asthma have a reduced ability to condition air. Because individuals with asthma usually have inflammation in the nose, we hypothesized that treatment with an intranasal steroid would reduce nasal inflammation and further decrease nasal conditioning capacity. We performed a randomized, double blind, placebo-controlled, 2-way crossover study on 20 subjects with asthma comparing the effect of treatment with intranasal budesonide for 2 weeks on nasal conditioning. Treatment with budesonide caused no significant effect on nasal conditioning as compared with placebo. When we evaluated the subgroup of nonsmoking subjects, budesonide caused a significant reduction in nasal conditioning. We speculate that nasal inflammation in nonsmoking individuals with asthma increases the conditioning capacity and reducing it with an intranasal steroid worsens the ability of the nose to condition air. In addition, smoking causes an increase in nasal conditioning capacity by non–steroid-dependent factors. These observations help us understand the pathophysiology of nasal conditioning, but do not negate the positive clinical benefits of budesonide on treating nasal inflammation.
Salvage Chemotherapy in Recurrent Ovarian Cancer: a Combination of Gemcitabine and Treosulfan is Equally Active in Platinum-Resistant and Platinum-Sensitive Disease
Authors: C.M. Kurbacher, S. Herz, G. Wessling, O. Horn, S. Sperling, J.A. Kurbacher
Journal: Annals of Oncology (2014)
Combination Chemotherapy in Lymphosarcoma and Reticulum Cell Sarcoma
Authors: BARTH HOOGSTRATEN, ALBERT H. OWENS, RAYMOND E. LENHARD, OLIVER J. GLIDEWELL, LOUIS A. LEONE, KENNETH B. OLSON, JOHN B. HARLEY, STUART R. TOWNSEND, SHERWOOD P. MILLER, CHARLES L. SPURR
Journal: Blood (1969)
Cancer Research Advocacy: Past, Present, and Future
Authors: Jane Perlmutter, Shannon K. Bell, Gwen Darien
Journal: Cancer Research (2013)

In this article, we present a brief history of cancer advocacy and discuss the variety of ways advocates have become involved in cancer research and subsequently present principles that establish a framework for successful research advocacy based on a review of many early initiatives coupled with our knowledge as long-time cancer advocates. Challenges to effective advocacy are described, and recommendations for increasing meaningful contributions by research advocates are proposed. The purpose of this article is to discuss the exciting field of research advocacy and to help shape a more productive future for advocates and their scientific collaborators.
Efficacy of FOLFIRI-3 (irinotecan D1,D3 combined with LV5-FU) or other irinotecan-based regimens in oxaliplatin-pretreated metastatic colorectal cancer in the GERCOR OPTIMOX1 study
Authors: F.-C. Bidard, C. Tournigand, T. André, M. Mabro, A. Figer, A. Cervantes, G. Lledo, L. Bengrine-Lefevre, F. Maindrault-Goebel, C. Louvet, A. de Gramont
Journal: Annals of Oncology (2009)
The Role of the Hedgehog Signaling Pathway in the Development of Basal Cell Carcinoma and Opportunities for Treatment
Authors: Ivor Caro, Jennifer A. Low
Journal: Clinical Cancer Research (2010)

The hedgehog (Hh) signaling pathway plays an important role in embryogenesis across multiple species. Its activity is reduced or absent in adult organisms. However, activation of the pathway has been shown to be a factor in the development of a number of human malignancies and inhibition of the pathway is being investigated as a potential treatment for multiple cancers. The most extensively investigated and best characterized is basal cell carcinoma (BCC), which occurs in both an inherited form (basal cell nevus syndrome or Gorlin's syndrome) and a sporadic form. Sporadic BCCs are the most common human malignancy. There is recent data available on the use of a small molecule inhibitor of the pathway in BCC.
The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists
Authors: Da Wei Huang, Brad T Sherman, Qina Tan, Jack R Collins, W Gregory Alvord, Jean Roayaei, Robert Stephens, Michael W Baseler, H Clifford Lane, Richard A Lempicki
Journal: Genome biology (2007)

The DAVID Gene Functional Classification Tool http://david.abcc.ncifcrf.gov uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context.
A Self-Fulfilling Prophecy
Authors: Subodh Verma, Chao-Hung Wang, Shu-Hong Li, Aaron S. Dumont, Paul W.M. Fedak, Mitesh V. Badiwala, Bikramjit Dhillon, Richard D. Weisel, Ren-Ke Li, Donald A.G. Mickle, Duncan J. Stewart
Journal: Circulation (2002)

Background— Given the central importance of nitric oxide (NO) in the development and clinical course of cardiovascular diseases, we sought to determine whether the powerful predictive value of C-reactive protein (CRP) might be explained through an effect on NO production. Methods and Results— Endothelial cells (ECs) were incubated with recombinant CRP (0 to 100 μg/mL, 24 hours), and NO and cyclic guanosine monophosphate (cGMP) production was assessed. The effects of CRP on endothelial NO synthase (eNOS) protein, mRNA expression, and mRNA stability were also examined. In a separate study, the effects of CRP (25 μg/mL) on EC cell survival, apoptosis, and in vitro angiogenesis were evaluated. Incubation of ECs with CRP resulted in a significant inhibition of basal and stimulated NO release, with concomitant reductions in cGMP production. CRP caused a marked downregulation of eNOS mRNA and protein expression. Actinomycin D studies suggested that eNOS downregulation was related to decreased mRNA stability. In conjunction with a decrease in NO production, CRP inhibited both basal and vascular endothelial growth factor–stimulated angiogenesis as assessed by EC migration and capillary-like tube formation. CRP did not induce EC survival but did, however, promote apoptosis in a NO-dependent fashion. Conclusions— CRP, at concentrations known to predict adverse vascular events, directly quenches the production of the NO, in part, through posttranscriptional effect on eNOS mRNA stability. Diminished NO bioactivity, in turn, inhibits angiogenesis, an important compensatory mechanism in chronic ischemia. Through decreasing NO synthesis, CRP may facilitate the development of diverse cardiovascular diseases. Risk reduction strategies designed to lower plasma CRP may be effective by improving NO bioavailability.
Aberrant Cytokine Production by Nonmalignant Cells in the Pathogenesis of Myeloproliferative Tumors and Response to JAK Inhibitor Therapies
Authors: Laura Belver, Adolfo A. Ferrando
Journal: Cancer Discovery (2015)

Abstract Summary: Kleppe and colleagues use detailed cytokine profiling analyses to investigate the role of aberrant proinflammatory cytokine secretion in the pathogenesis of myeloproliferative neoplasms. Their analyses implicate constitutive activation of STAT3 in both malignant and nonmalignant bone marrow cell populations as a driver of aberrant cytokine secretion and as a cellular target mediating the therapeutic activity of ruxolitinib. Cancer Discov; 5(3); 234–6. ©2015 AACR. See related article by Kleppe and colleagues, p. 316
Low Serum Ferroxidase I Activity Is Associated With Mortality in Heart Failure and Related to Both Peroxynitrite-Induced Cysteine Oxidation and Tyrosine Nitration of Ceruloplasmin
Authors: Aderville Cabassi, Simone Maurizio Binno, Stefano Tedeschi, Valerie Ruzicka, Simona Dancelli, Rossana Rocco, Vanni Vicini, Pietro Coghi, Giuseppe Regolisti, Alberto Montanari, Enrico Fiaccadori, Paolo Govoni, Massimo Piepoli, Jacques de Champlain
Journal: Circulation Research (2014)

Ceruloplasmin antioxidant function is mainly related to its ferroxidase I (FeOxI) activity, which influences iron-dependent oxidative and nitrosative radical species generation. Peroxynitrite, whose production is increased in heart failure (HF), can affect ceruloplasmin antioxidant function through amino acid modification.We investigated the relationship between FeOxI and ceruloplasmin tyrosine and cysteine modification and explored in a cohort of patients with HF the potential clinical relevance of serum FeOxI.In patients with chronic HF (n=96, 76 ± 9 years; New York Heart Association class, 2.9 ± 0.8) and age-matched controls (n=35), serum FeOxI, FeOxII, ceruloplasmin, nitrotyrosine-bound ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were measured, and the patients were followed up for 24 months. Ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were increased in HF versus controls. FeOxI was decreased in HF (-20%) and inversely related to nitrotyrosine-bound ceruloplasmin (r, -0.305; P=0.003). In HF, FeOxI lower tertile had a mortality rate doubled compared with middle-higher tertiles. FeOxI emerged as a mortality predictor (hazard ratio, 2.95; 95% confidence intervals [1.29-6.75]; P=0.011) after adjustment for age, sex, hypertension, smoking, sodium level, estimated glomerular filtration rate, and high-sensitivity C-reactive protein. In experimental settings, peroxynitrite incubation of serum samples and isolated purified ceruloplasmin reduced FeOxI activity while increasing ceruloplasmin tyrosine nitration and cysteine thiol oxidation. Reduced glutathione prevented peroxynitrite-induced FeOxI drop, tyrosine nitration, and cysteine oxidation; flavonoid(-)-epicatechin, which prevented ceruloplasmin tyrosine nitration but not cysteine oxidation, partially impeded peroxynitrite-induced FeOxI drop.Reduced activity of serum FeOxI is associated with ceruloplasmin nitration and reduced survival in patients with HF. Both ceruloplasmin tyrosine nitration and cysteine thiol oxidation may be operant in vivo in peroxynitrite-induced FeOxI activity inhibition.
<i>In utero</i> Exposure of Mice to Dibenzo[<i>a,l</i>]Pyrene Produces Lymphoma in the Offspring: Role of the Aryl Hydrocarbon Receptor
Authors: Zhen Yu, Christiane V. Loehr, Kay A. Fischer, Mandy A. Louderback, Sharon K. Krueger, Roderick H. Dashwood, Nancy I. Kerkvliet, Clifford B. Pereira, Jamie E. Jennings-Gee, Stephanie T. Dance, Mark Steven Miller, George S. Bailey, David E. Williams
Journal: Cancer Research (2006)

Abstract Lymphoma and leukemia are the most common cancers in children and young adults; in utero carcinogen exposure may contribute to the etiology of these cancers. A polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), was given to pregnant mice (15 mg/kg body weight, gavage) on gestation day 17. Significant mortalities in offspring, beginning at 12 weeks of age, were observed due to an aggressive T-cell lymphoblastic lymphoma. Lymphocytes invaded numerous tissues. All mice surviving 10 months, exposed in utero to DBP, exhibited lung tumors; some mice also had liver tumors. To assess the role of the aryl hydrocarbon receptor (AHR) in DBP transplacental cancer, B6129SF1/J (AHRb-1/d, responsive) mice were crossed with strain 129S1/SvIm (AHRd/d, nonresponsive) to determine the effect of maternal and fetal AHR status on carcinogenesis. Offspring born to nonresponsive mothers had greater susceptibility to lymphoma, irrespective of offspring phenotype. However, when the mother was responsive, an AHR-responsive phenotype in offspring increased mortality by 2-fold. In DBP-induced lymphomas, no evidence was found for TP53, β-catenin, or Ki-ras mutations but lung adenomas of mice surviving to 10 months of age had mutations in Ki-ras codons 12 and 13. Lung adenomas exhibited a 50% decrease and a 35-fold increase in expression of Rb and p19/ARF mRNA, respectively. This is the first demonstration that transplacental exposure to an environmental PAH can induce a highly aggressive lymphoma in mice and raises the possibility that PAH exposures to pregnant women could contribute to similar cancers in children and young adults. (Cancer Res 2006; 66(2): 755-62)
A vascular bed–specific pathway regulates cardiac expression of endothelial nitric oxide synthase
Authors: Pascale V. Guillot, Jason Guan, Lixin Liu, Jan A. Kuivenhoven, Robert D. Rosenberg, William C. Sessa, William C. Aird
Journal: Journal of Clinical Investigation (1999)

The endothelial nitric oxide synthase (eNOS) gene is induced by a variety of extracellular signals under both in vitro and in vivo conditions. To gain insight into the mechanisms underlying environmental regulation of eNos expression, transgenic mice were generated with the 1,600-bp 5' flanking region of the human eNos promoter coupled to the coding region of the LacZ gene. In multiple independent lines of mice, transgene expression was detected within the endothelium of the brain, heart, skeletal muscle, and aorta. beta-galactosidase activity was consistently absent in the vascular beds of the liver, kidney, and spleen. In stable transfection assays of murine endothelial progenitor cells, the 1,600-bp promoter region was selectively induced by conditioned media from cardiac myocytes, skeletal myocytes, and brain astrocytes. Cardiac myocyte-mediated induction was partly abrogated by neutralizing anti-platelet-derived growth factor (PDGF) antibodies. In addition, promoter activity was upregulated by PDGF-AB. Analysis of promoter deletions revealed that a PDGF response element lies between -744 and -1,600 relative to the start site of transcription, whereas a PDGF-independent cardiac myocyte response element is present within the first 166 bp of the 5' flanking region. Taken together, these results suggest that the eNos gene is regulated in the cardiac endothelium by both a PDGF-dependent and PDGF-independent microvascular bed-specific signaling pathway.
Visual Guidance in Control of Grasping
Authors: Peter Janssen, Hansjörg Scherberger
Journal: Annual Review of Neuroscience (2015)

Humans and other primates possess a unique capacity to grasp and manipulate objects skillfully, a facility pervasive in everyday life that has undoubtedly contributed to the success of our species. When we reach and grasp an object, various cortical areas in the parietal and frontal lobes work together effortlessly to analyze object shape and position, transform this visual information into useful motor commands, and implement these motor representations to preshape the hand before contact with the object is made. In recent years, a growing number of studies have investigated the neural circuits underlying object grasping in both the visual and motor systems of the macaque monkey. The accumulated knowledge not only helps researchers understand how object grasping is implemented in the primate brain but may also contribute to the development of novel neural interfaces and neuroprosthetics.
SPAK-Knockout Mice Manifest Gitelman Syndrome and Impaired Vasoconstriction
Authors: Sung-Sen Yang, Yi-Fen Lo, Chin-Chen Wu, Shu-Wha Lin, Chien-Ju Yeh, Pauling Chu, Huey-Kang Sytwu, Shinichi Uchida, Sei Sasaki, Shih-Hua Lin
Journal: Journal of the American Society of Nephrology (2010)

Polymorphisms in the gene encoding sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) associate with hypertension susceptibility in humans. SPAK interacts with WNK kinases to regulate the Na(+)-K(+)-2Cl(-) and Na(+)-Cl(-) co-transporters [collectively, N(K)CC]. Mutations in WNK1/4 and N(K)CC can cause changes in BP and dyskalemia in humans, but the physiologic role of SPAK in vivo is unknown. We generated and analyzed SPAK-null mice by targeting disruption of exons 9 and 10 of SPAK. Compared with SPAK(+/+) littermates, SPAK(+/-) mice exhibited hypotension without significant electrolyte abnormalities, and SPAK(-/-) mice not only exhibited hypotension but also recapitulated Gitelman syndrome with hypokalemia, hypomagnesemia, and hypocalciuria. In the kidney tissues of SPAK(-/-) mice, the expression of total and phosphorylated (p-)NCC was markedly decreased, but that of p-OSR1, total NKCC2, and p-NKCC2 was significantly increased. We observed a blunted response to thiazide but normal response to furosemide in SPAK(-/-) mice. In aortic tissues, total NKCC1 expression was increased but p-NKCC1 was decreased in SPAK-deficient mice. Both SPAK(+/-) and SPAK(-/-) mice had impaired responses to the selective α(1)-adrenergic agonist phenylephrine and the NKCC1 inhibitor bumetanide, suggesting that impaired aortic contractility may contribute to the hypotension of SPAK-null mice. In summary, SPAK-null mice have defects of NCC in the kidneys and NKCC1 in the blood vessels, leading to hypotension through renal salt wasting and vasodilation. SPAK may be a promising target for antihypertensive therapy.