tbuckley/cabot-search huggingface dataset:
Protein Kinase D1 Inhibits Cell Proliferation through Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Secretion in Prostate Cancer
Authors: M. Helal Uddin Biswas, Cheng Du, Chuanyou Zhang, Juerg Straubhaar, Lucia R. Languino, K.C. Balaji
Journal: Cancer Research (2010)

Abstract We and others previously showed that protein kinase D1 (PKD1) is downregulated in several cancers including prostate; interacts with E-cadherin, a major cell adhesion epithelial protein; and causes increased cell aggregation and decreased motility of prostate cancer cells. In this study, we show that PKD1 complexes with β3-integrin, resulting in activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase–ERK pathway, which causes increased production of matrix metalloproteinase (MMP)-2 and MMP-9, that is associated with shedding of soluble 80 kDa E-cadherin extracellular domain. Interestingly, decreased cell proliferation following PKD1 transfection was rescued by MMP-2 and MMP-9 inhibitors and augmented by recombinant MMP-2 (rMMP-2) and rMMP-9 proteins, suggesting an antiproliferative role for MMPs in prostate cancer. Translational studies by in silico analysis of publicly available DNA microarray data sets show a significant direct correlation between PKD1 and MMP-2 expression in human prostate tissues. The study shows a novel mechanism for antiproliferative effects of PKD1, a protein of emerging translational interest in several human cancers, through increased production of MMP-2 and MMP-9 in cancer cells. Cancer Res; 70(5); 2095–104
Pleiotropic Approach to Graft-Versus-Host Disease
Authors: Areej El-Jawahri, Yi-Bin Chen
Journal: Journal of Clinical Oncology (2013)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2013.52.8182 Journal of Clinical Oncology - published online before print October 28, 2013 PMID: 24166516 Pleiotropic Approach to Graft-Versus-Host Disease Areej El-JawahrixAreej El-JawahriSearch for articles by this author , Yi-Bin ChenxYi-Bin ChenSearch for articles by this author Show More Massachusetts General Hospital, and Dana-Farber Cancer Institute, Boston MA https://doi.org/10.1200/JCO.2013.52.8182 First Page Full Text PDF Figures and Tables © 2013 by American Society of Clinical Oncology
Biologic characterization of a secondary glioblastoma with extracranial progression and systemic metastasis
Authors: Shigeo Ueda, Toshihiro Mineta, Kenji Suzuyama, Makoto Furuta, Tetsuya Shiraishi, Kazuo Tabuchi
Journal: Neuro-Oncology (2003)

Glioblastomas rarely metastasize outside the CNS. We biologically characterized a case of secondary glioblastoma associated with extracranial progression and distant metastasis. A 42-year-old male patient was subjected to craniotomy for a left temporal tumor (astrocytoma grade II) and subsequently underwent another 3 craniotomies due to tumor recurrences. At the third craniotomy, extracranial progression was noted, and the tumor was classified as a glioblastoma. In order to pinpoint the genes expressed differentially in the intracranial primary tumor and the metastatic tumors, we used cDNA microarray. The patterns of gene expression in these 2 samples were highly similar, suggesting that the mechanism of metastasis was direct infiltration of tumor cells into extracranial blood vessels. Insulin-like growth factor binding protein-2 was overexpressed in both primary and metastatic tumors. Immunohistochemical studies of DNA-dependent protein kinase, which participates in the repair of DNA, was strongly positive in the samples obtained at the first and second operations, but the positive rates were markedly reduced in the specimens obtained at the third and fourth operations. These results suggest that insulin-like growth factor binding protein-2 and deficiency of DNA-dependent protein kinase proteins promoted tumor progression in the present case.
Centripetal spread of arterial collateral endothelial cell hyperplasia after renal artery stenosis in the rat.
Authors: N K Hollenberg, T Odori
Journal: Circulation Research (1987)

The factors responsible for collateral arterial growth after major artery occlusion remain obscure, despite their importance for tissue survival. An increase in endothelial cell labelling with tritiated thymidine, as an index of collateral arterial growth, occurs early after renal artery occlusion. Our working premise was that an increase in endothelial cell labelling would occur simultaneously throughout the length of the collateral arteries if biophysical factors related to blood flow were the responsible mechanism, because blood flow must be increased simultaneously throughout the length of the small, preformed collateral arterial vessels. On the other hand, if the information spread from the ischemic zone, one would anticipate centripetal spread of the endothelial cell hyperplasia in a retrograde direction from the ischemic zone. With the periureteric collateral arterial supply as the model, we performed serial studies of tritiated thymidine labelling following renal artery stenosis in the rat. As anticipated, endothelial cell labelling rose sharply within 24 to 48 hours, first evident in the area immediately adjacent to the renal hilum. Thereafter, a progressive, time-related centripetal gradient in endothelial cell tritiated thymidine labelling occurred (p less than 0.01). These findings indicate that the factors responsible for endothelial cell hyperplasia are less related to blood flow in the lumen than to downstream, ischemic events. Although the mechanism responsible for the centripetal spread remains speculative, the communication system is likely to involve cell-to-cell contact in the vessel wall.
A Small-Molecule E2F Inhibitor Blocks Growth in a Melanoma Culture Model
Authors: Yihong Ma, Courtney A. Kurtyka, Sandhya Boyapalle, Shen-Shu Sung, Harshani Lawrence, Wayne Guida, W. Douglas Cress
Journal: Cancer Research (2008)

Abstract HLM006474 was identified using a computer-based virtual screen and the known crystal structure of the DNA-bound E2F4/DP2 heterodimer. Treatment of multiple cell lines with HLM006474 resulted in the loss of intracellular E2F4 DNA-binding activity as measured by electrophoretic mobility shift assay within hours. Overnight exposure to HLM006474 resulted in down-regulation of total E2F4 protein as well as known E2F targets. The effects of HLM006474 treatment on different cell lines varied but included a reduction in cell proliferation and an increase in apoptosis. HLM006474 induced apoptosis in a manner distinct from cisplatin and doxorubicin. E2F4-null mouse embryonic fibroblasts were less sensitive than wild-type counterparts to the apoptosis-inducing activity of the compound, revealing its biological specificity. A375 cells were extremely sensitive to the apoptosis-inducing activity of the compound in two-dimensional culture, and HLM006474 was a potent inhibitor of melanocytes proliferation and subsequent invasion in a three-dimensional tissue culture model system. Together, these results suggest that interference with E2F activity using small molecules may have clinical application in cancer therapy. [Cancer Res 2008;68(15):6292–9]
The Probiotic Preparation, VSL#3 Induces Remission in Patients With Mild-to-Moderately Active Ulcerative Colitis
Authors: Ajit Sood, Vandana Midha, Govind K. Makharia, Vineet Ahuja, Dinesh Singal, Pooja Goswami, Rakesh K. Tandon
Journal: Clinical Gastroenterology and Hepatology (2009)
Successful Lateral Transfer Requires Codon Usage Compatibility Between Foreign Genes and Recipient Genomes
Authors: Arturo Medrano-Soto, Gabriel Moreno-Hagelsieb, Pablo Vinuesa, J. Andrés Christen, Julio Collado-Vides
Journal: Molecular Biology and Evolution (2004)

We present evidence supporting the notion that codon usage (CU) compatibility between foreign genes and recipient genomes is an important prerequisite to assess the selective advantage of imported functions, and therefore to increase the fixation probability of horizontal gene transfer (HGT) events. This contrasts with the current tendency in research to predict recent HGTs in prokaryotes by assuming that acquired genes generally display poor CU. By looking at the CU level (poor, typical, or rich) exhibited by putative xenologs still resembling their original CU, we found that most alien genes predominantly present typical CU immediately upon introgression, thereby suggesting that the role of CU amelioration in HGT has been overemphasized. In our strategy, we first scanned a representative set of 103 complete prokaryotic genomes for all pairs of candidate xenologs (exported/imported genes) displaying similar CU. We applied additional filtering criteria, including phylogenetic validations, to enhance the reliability of our predictions. Our approach makes no assumptions about the CU of foreign genes being typical or atypical within the recipient genome, thus providing a novel unbiased framework to study the evolutionary dynamics of HGT.
A surface charge-switchable and folate modified system for co-delivery of proapoptosis peptide and p53 plasmid in cancer therapy
Authors: Si Chen, Lei Rong, Qi Lei, Peng-Xi Cao, Si-Yong Qin, Di-Wei Zheng, Hui-Zhen Jia, Jing-Yi Zhu, Si-Xue Cheng, Ren-Xi Zhuo, Xian-Zheng Zhang
Journal: Biomaterials (2015)
CD2 is involved in maintenance and reversal of human alloantigen-specific clonal anergy.
Authors: V A Boussiotis, G J Freeman, J D Griffin, G S Gray, J G Gribben, L M Nadler
Journal: The Journal of Experimental Medicine (1994)

Induction and maintenance of a state of T cell unresponsiveness to specific alloantigen would have significant implications for human organ transplantation. Using human histocompatibility leukocyte antigen DR7-specific helper T cell clones, we demonstrate that blockade of the B7 family of costimulatory molecules is sufficient to induce alloantigen-specific T cell clonal anergy. Anergized cells do not respond to alloantigen and a variety of costimulatory molecules, including B7-1, B7-2, intercellular adhesion molecule-1 (ICAM-1), and lymphocyte function-associated molecule (LFA)-3. However, after culture in exogenous interleukin (IL)-2 for at least 7 d, anergized cells can respond to alloantigen in the presence of LFA-3. LFA-3 costimulation subsequently restores responsiveness to alloantigen in the presence of previously insufficient costimulatory signals. Expression of CD2R epitope is downregulated on anergic cells and is restored after 7 d of IL-2 culture. The loss of the CD2R is temporally associated with the inability of anergized cells to respond to LFA-3. These results suggest that in addition to blockade of B7 family members, inhibition of CD2 and, potentially, other costimulatory pathways that might reverse anergy will be necessary to maintain prolonged alloantigen-specific tolerance.
Plasminogen Is an Important Regulator in the Pathogenesis of a Murine Model of Asthma
Authors: Carmen M. Swaisgood, Mark A. Aronica, Shadi Swaidani, Edward F. Plow
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Asthma is a syndrome whose common pathogenic expression is inflammation of the airways. Plasminogen plays an important role in cell migration and is also implicated in tissue remodeling, but its role in asthma has not been defined.Objectives: To test whether plasminogen is a critical component in the development of asthma.Methods: We used a mouse model of ovalbumin-induced pulmonary inflammation in Plg+/+, Plg+/−, and Plg−/− mice.Measurements and Main Results: The host responses measured included lung morphometry, and inflammatory mediators and cell counts were assessed in bronchoalveolar lavage fluid. Bronchoalveolar lavage demonstrated a marked increase in eosinophils and lymphocytes in ovalbumin-treated Plg+/+ mice, which were reduced to phosphate-buffered saline–treated control levels in Plg+/− or Plg−/− mice. Lung histology revealed peribronchial and perivascular leukocytosis, mucus production, and increased collagen deposition in ovalbumin-treated Plg+/+ but not in Plg+/− or Plg−/− mice. IL-5, tumor necrosis factor-α, and gelatinases, known mediators of asthma, were detected in bronchoalveolar lavage fluid of ovalbumin-treated Plg+/+ mice, yet were reduced in Plg−/− mice. Administration of the plasminogen inhibitor, tranexamic acid, reduced eosinophil and lymphocyte numbers, mucus production, and collagen deposition in the lungs of ovalbumin-treated Plg+/+ mice.Conclusions: The decreased inflammation in the lungs of Plg−/− mice and its blockade with a plasminogen inhibitor indicate that plasminogen plays an important role in orchestrating the asthmatic response and suggests that plasminogen may be a therapeutic target for the treatment of asthma.
Provocative Questions Initiative to Fund Innovative Cancer Research
Authors: S. Benowitz
Journal: JNCI Journal of the National Cancer Institute (2012)

If cancer is primarily a disease of aging, caused by a lifetime of accumulating genetic mutations, why do kids get cancer? Why do animals such as mice, with an average lifespan of two years, have a much higher cancer rate than animals that live longer like turtles? Can evolutionary biology and Darwinian selection provide insights for overcoming drug resistance, and turn some cancer into a chronic disease? Difficult, complicated questions all– and examples of what the National Cancer Institute (NCI) has dubbed “Provocative Questions.” NCI has assembled 24 such “potentially game-changing scientific questions that could influence the directions taken by NCI-sponsored research in the future,” according to its website, issuing a formal Request for Applications (RFA) that has many in the cancer research community buzzing with curiosity. The RFA included $15 million to fund 25 standard four-year R01 awards and 10 exploratory two-year, R21 awards in 2012. Decisions on awards are tentatively scheduled to be announced in June.
MicroRNA-23 Restricts Cardiac Valve Formation by Inhibiting <i>Has2</i> and Extracellular Hyaluronic Acid Production
Authors: Anne Karine Lagendijk, Marie Jose Goumans, Silja Barbara Burkhard, Jeroen Bakkers
Journal: Circulation Research (2011)

Since their discovery almost 20 years ago, microRNAs have been shown to perform essential roles during tissue development and disease. Although roles for microRNAs in the myocardium during embryo development and cardiac disease have been demonstrated, very little is know about their role in the endocardium or during cardiac valve formation.To study the role of microRNAs in cardiac valve formation.We show that zebrafish dicer mutant embryos, lacking mature miRNAs, form excessive endocardial cushions. By screening miRNAs expressed in the heart, we found that miR-23 is both necessary and sufficient for restricting the number of endocardial cells that differentiate into endocardial cushion cells. In addition, in mouse endothelial cells, miR-23 inhibited a transforming growth factor-β-induced endothelial-to-mesenchymal transition. By in silico screening of expression data with predicted miR-23 target sites combined with in vivo testing, we identified hyaluronic acid synthase 2 (Has2), Icat, and Tmem2 as novel direct targets of miR-23. Finally, we demonstrate that the upregulation of Has2, an extracellular remodeling enzyme required for endocardial cushion and valve formation, is responsible for the excessive endocardial cushion cell differentiation in dicer mutants.MiR-23 in the embryonic heart is required to restrict endocardial cushion formation by inhibiting Has2 expression and extracellular hyaluronic acid production.
Multimarker Prediction of Coronary Heart Disease Risk
Authors: Hyeon Chang Kim, Philip Greenland, Jacques E. Rossouw, JoAnn E. Manson, Barbara B. Cochrane, Norman L. Lasser, Marian C. Limacher, Donald M. Lloyd-Jones, Karen L. Margolis, Jennifer G. Robinson
Journal: Journal of the American College of Cardiology (2010)
Identification of a B-cell surface structure involved in antigen-dependent triggering: absence of this structure on B cells from CBA/N mutant mice.
Authors: B Huber, R K Gershon, H Cantor
Journal: The Journal of Experimental Medicine (1977)

CBA/N mice have an X-linked B-cell maturation defect which is reflected in part in an absence or dysfunction of a subclass of mature B cells. We have immunized the defective male offspring of the mating (CBA/N female X BALB/c male) with BALB/c spleen cells. The resulting antiserum (alphaLyb3) selectively reacts with a component on the surface of a portion of B cells from a panel of H-2 different mouse strains. Binding of alphaLyb3 serum to this B-cell subclass results in substantial (10- to 20-fold) enhancement of the antibody response to low doses of SRBC. Both binding and enhancing activity are removed by absorption with B cells from B6 and BALB/c, but not CBA/N mice. Absorption of the serum with bone marrow cells, T cells, or thymocytes from Lyb3+ strains does not remove activity. Since the enhanced plaque-forming cell (PFC) responses are specific for the immunizing antigen, and since no PFC response is produced by injection of the antiserum alone, this enhancement probably reflects a second signal produced by specific interaction between antibody and the surface Lyb3 component. Moreover, this signal can partially replace the requirement for T cells in the production of antibody to a "thymus-dependent" antigen. These findings (taken in conjunction with the previously described immune defects in CBA/N mice and other studies of B-cell maturation) suggest to us that Lyb3 is a cell surface component expressed selectively on a mature B-cell subclass. This component is important in B-cell triggering by antigen and fails to develop in CBA/N mice, due to a dysfunction of a regulatory gene on the CBA/N X chromosome.
Intercomparison of retrospective radon detectors.
Authors: R W Field, D J Steck, M A Parkhurst, J A Mahaffey, M C Alavanja
Journal: Environmental Health Perspectives (1999)

We performed both a laboratory and a field intercomparison of two novel glass-based retrospective radon detectors previously used in major radon case-control studies performed in Missouri and Iowa. The new detectors estimate retrospective residential radon exposure from the accumulation of a long-lived radon decay product, (210)Pb, in glass. The detectors use track registration material in direct contact with glass surfaces to measure the alpha-emission of a (210)Pb-decay product, (210)Po. The detector's track density generation rate (tracks per square centimeter per hour) is proportional to the surface alpha-activity. In the absence of other strong sources of alpha-emission in the glass, the implanted surface alpha-activity should be proportional to the accumulated (210)Po, and hence to the cumulative radon gas exposure. The goals of the intercomparison were to a) perform collocated measurements using two different glass-based retrospective radon detectors in a controlled laboratory environment to compare their relative response to implanted polonium in the absence of environmental variation, b) perform collocated measurements using two different retrospective radon progeny detectors in a variety of residential settings to compare their detection of glass-implanted polonium activities, and c) examine the correlation between track density rates and contemporary radon gas concentrations. The laboratory results suggested that the materials and methods used by the studies produced similar track densities in detectors exposed to the same implanted (210)Po activity. The field phase of the intercomparison found excellent agreement between the track density rates for the two types of retrospective detectors. The correlation between the track density rates and direct contemporary radon concentration measurements was relatively high, considering that no adjustments were performed to account for either the residential depositional environment or glass surface type. Preliminary comparisons of the models used to translate track rate densities to average long-term radon concentrations differ between the two studies. Further calibration of the retrospective detectors' models for interpretation of track rate density may allow the pooling of studies that use glass-based retrospective radon detectors to determine historic residential radon exposures.
Duration of treatment for urinary tract infections in children.
Authors: J M Stansfeld
Journal: BMJ (1975)

In a double-blind trial 45 children aged 6 months to 14 years with Escherichia coli infections of the urinary tract were given co-trimoxazole for two weeks and then allotted at random to one of two treatment groups for the remainder of six months; one continued with the active drug and the other with dummy tablets of identical appearance. Of the 24 children who took co-trimoxazole for two weeks and the 21 who took it for six months, 11 and 10, respectively, remained without further infections for at least a year. Over 90% of the reinfections occurred within five months of stopping the antibiotics, and the longer treatment did not cause any delay in their appearance. Thus probably a six-month course of treatment is no more likely to achieve a cure than a two-week course; nevertheless, no infection occurred during treatment, and there may be an advantage in continuing with antibiotics in small dosage.
Working with what we have: Options for myocardial infarct repair?
Authors: I DIXON
Journal: Cardiovascular Research (2007)

See article by Bruel et al.  [4]  (pages 400–408) in this issue. 

The classic mythological tale of the crimes of Prometheus in gifting mortal men with, among other things, the divine fire, serves to remind us never to anger anyone as powerful as Zeus. For his efforts, Prometheus was shackled to a mountain to be tormented daily by Zeus' pet eagle who, according to legend, preferred liver. Each subsequent evening, Prometheus' tissues regenerated, and the cycle of mechanical destruction and regeneration would repeat ad nauseum until finally Zeus regained a modicum of calm and released him. What is possibly more fascinating (and certainly much less gruesome) – the notion of rebuilding or regenerating the myocardium following either catastrophic myocyte loss (as in myocardial infarction or MI) or in progressive loss of contractile cells in various progressive cardiomyopathies – has long intrigued both clinical and basic investigators in cardiology and is currently stirring a considerable degree of interest and effort. In this vein a number of exciting developments have come to pass within the past 2years that deserve comment.

New myocytes in the heart: stem cells vs. stimulation of primordial cells. The putative “carrot” within the approach of cardiac regeneration includes the reversal of … 

*Tel.: +1 204 235 3419. idixon{at}sbrc.ca