tbuckley/cabot-search huggingface dataset:
Down-regulation of Cx43 by Retroviral Delivery of Small Interfering RNA Promotes an Aggressive Breast Cancer Cell Phenotype
Authors: Qing Shao, Hongling Wang, Elizabeth McLachlan, Gregory I.L. Veitch, Dale W. Laird
Journal: Cancer Research (2005)

Abstract Connexins are gap junction proteins that assemble into channels that mediate direct intercellular communication. Connexins are well-documented tumor suppressors and are thought to regulate both cell growth and differentiation. As previously reported, most human breast tumors and cell lines down-regulate gap junctions or have defective gap junctional intercellular communication. Furthermore, overexpression of connexins in breast cancer cells inhibits tumor growth in vivo. In this study, we hypothesize that controlled Cx43 down-regulation would induce breast tumor cells to acquire a more aggressive phenotype. Here we report that Cx43 was down-regulated in both normal rat kidney (NRK) cells and human breast cancer cell lines (MDA-MB-231 and Hs578T) by transfection with chemically synthesized small interfering RNA (siRNA) or short hairpin RNA generated from a retroviral infection. Furthermore, we show that retroviral delivery and expression of siRNA directed to different coding regions of Cx43 resulted in differential levels of Cx43 silencing and impaired gap junctional intercellular communication. Cx43-silenced Hs578T cells grew faster and were more migratory. Finally, Western blot analysis revealed that down-regulation of Cx43 resulted in decreased expression of thrombospondin-1, an antiangiogenesis molecule, and increased expression of vascular endothelial growth factor. Taken together, these results suggest that Cx43 is required for maintaining cell differentiation and the regulation of molecules important in angiogenesis.
A Novel Recurrent Chromosomal Inversion Implicates the Homeobox Gene<i>Dlx5</i>in T-Cell Lymphomas from Lck-Akt2 Transgenic Mice
Authors: Yinfei Tan, Roman A. Timakhov, Mamta Rao, Deborah A. Altomare, Jinfei Xu, Zemin Liu, Qingshen Gao, Suresh C. Jhanwar, Antonio Di Cristofano, David L. Wiest, Janice E. Knepper, Joseph R. Testa
Journal: Cancer Research (2008)

Abstract The oncogene v-akt was isolated from a retrovirus that induced murine thymic lymphomas. Transgenic mice expressing a constitutively activated form of the cellular homologue Akt2 specifically in immature T cells develop spontaneous thymic lymphomas. We hypothesized that tumors from these mice might exhibit oncogenic chromosomal rearrangements that cooperate with activated Akt2 in lymphomagenesis. Cytogenetic analysis revealed a recurrent clonal inversion of chromosome 6, inv(6), in thymic lymphomas from multiple transgenic founder lines, including one line in which 15 of 15 primary tumors exhibited this same rearrangement. Combined fluorescence in situ hybridization, PCR, and DNA sequence analyses showed that the distal inv(6) breakpoint resides at the T-cell receptor β chain locus, Tcrb. The proximal breakpoint maps to a region near a locus comprising the linked homeobox/transcription factor genes Dlx5 and Dlx6. Expression analysis of genes translocated to the vicinity of the Tcrb enhancer revealed that Dlx5 and Dlx6 are overexpressed in tumors exhibiting the inv(6). Experimental overexpression of Dlx5 in mammalian cells resulted in enhanced cell proliferation and increased colony formation, and clonogenic assays revealed cooperativity when both Dlx5 and activated Akt2 were coexpressed. In addition, DLX5, but not DLX6, was found to be abundantly expressed in three of seven human T-cell lymphomas tested. These findings suggest that the Dlx5 can act as an oncogene by cooperating with Akt2 to promote lymphomagenesis. [Cancer Res 2008;68(5):1296–302]
Jejunal mucosal appearances after total gastrectomy
Authors: J. M. Johnstone, J. F. Adams
Journal: Gut (1964)

EDITORIAL SYNOPSIS Villous atrophy was present in two out of 14 patients after total gastrectomy, one being associated with subserosal infiltration of secondary carcinoma, but the other patient showed only minor changes in biopsies taken further from the stoma.
Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma
Authors: Carolina P.B. Gracitelli, Gloria Liliana Duque-Chica, Marina Roizenblatt, Ana Laura de Araújo Moura, Balazs V. Nagy, Geraldine Ragot de Melo, Paula Delegrego Borba, Sérgio H. Teixeira, Sergio Tufik, Dora Fix Ventura, Augusto Paranhos
Journal: Ophthalmology (2015)
Which patients with ankylosing spondylitis should be treated with tumour necrosis factor inhibiting therapy? A survey among Dutch rheumatologists
Authors: R Landewe
Journal: Annals of the Rheumatic Diseases (2004)

To determine the criteria considered important by Dutch rheumatologists in judging whether a patient with ankylosing spondylitis should start tumour necrosis factor (TNF) blocking therapy.19 Dutch rheumatologists were asked to prioritise various demographic and clinical features for their importance in judging whether a patient should be treated with TNF blocking therapy. In addition, nine Dutch physicians who had referred patients with ankylosing spondylitis for inclusion in an ongoing long term observational study (OASIS) were asked to determine on the basis of case record review for each of their patients whether or not TNF blocking therapy would be considered appropriate.The variables considered most important were: rate of development of functional impairment; physician's global assessment of current disease activity; physician's global assessment of cumulative disease activity; presence of hip arthritis; physician's global assessment of disease severity. Analysis of the OASIS data (79 patients) showed that patients in whom TNF blocking therapy was considered justified (n = 24; 30%) differed significantly from those in whom it was not considered justified in: patient reported disease activity; functional impairment; spinal mobility; radiographic damage score. Multivariate analysis showed that male sex, function, and radiographic damage were the only independent determinants of a decision to start TNF blocking drugs.Physicians reported that disease activity, function, and severity were critically important in judging whether to start TNF blocking therapy. In practice, they based their decision more on severity than on activity. They were able to select patients with a high level of radiographic damage, which suggests that this feature captures other domains such as disease activity, spinal mobility, and function.
Tumors Sound the Alarmin(s)
Authors: Seth B. Coffelt, Aline B. Scandurro
Journal: Cancer Research (2008)

Abstract Recent evidence suggests that inflammatory molecules play critical roles in the development and progression of numerous tumors. However, one specific group of inflammatory molecules whose importance has been established in host immune responses, termed alarmins, has been largely overlooked in cancer biology. The function of several alarmins—including the defensins, LL-37, and HMGB1—in tumor development, progression, or suppression is discussed here. Taken together, these studies indicate that alarmins represent potential new targets for manipulation in a variety of tumors. [Cancer Res 2008;68(16):6482–5]
Adverse Impact of Bleeding on Prognosis in Patients With Acute Coronary Syndromes
Authors: John W. Eikelboom, Shamir R. Mehta, Sonia S. Anand, Changchun Xie, Keith A.A. Fox, Salim Yusuf
Journal: Circulation (2006)

The use of multiple antithrombotic drugs and aggressive invasive strategies has increased the risk of major bleeding in acute coronary syndrome (ACS) patients. It is not known to what extent bleeding determines clinical outcome.Using Cox proportional-hazards modeling, we examined the association between bleeding and death or ischemic events in 34,146 patients with ACS enrolled in the Organization to Assess Ischemic Syndromes and the Clopidogrel in Unstable Angina to Prevent Recurrent Events studies. Patients with major bleeding were older, more often had diabetes or a history of stroke, had a lower blood pressure and higher serum creatinine, more often had ST-segment changes on the presenting ECG, and had a 5-fold-higher incidence of death during the first 30 days (12.8% versus 2.5%; P < 0.0001) and a 1.5-fold-higher incidence of death between 30 days and 6 months (4.6% versus 2.9%; P = 0.002). Major bleeding was independently associated with an increased hazard of death during the first 30 days (hazard ratio, 5.37; 95% CI, 3.97 to 7.26; P < 0.0001), but the hazard was much weaker after 30 days (hazard ratio, 1.54; 95% CI, 1.01 to 2.36; P = 0.047). The association was consistent across subgroups according to cointerventions during hospitalization, and there was an increasing risk of death with increasing severity of bleeding (minor less than major less than life-threatening; P for trend = 0.0009). A similar association was evident between major bleeding and ischemic events, including myocardial infarction and stroke.In ACS patients without persistent ST-segment elevation, there is a strong, consistent, temporal, and dose-related association between bleeding and death. These data should lead to greater awareness of the prognostic importance of bleeding in ACS and should prompt evaluation of strategies to reduce bleeding and thereby improve clinical outcomes.
Fine Needle Aspiration Is a Feasible and Accurate Technique in the Diagnosis of Lymphoma
Authors: R. Marshall Austin, George G. Birdsong, Mary K. Sidawy, David B. Kaminsky, Barbara D. Benstein, Edmund S. Cibas, Dina R. Mody, Barbara J. Guidos, Ann T. Moriarty, David L. Rimm, Hormoz Ehya, Michael S. Facik, Lydia P. Howell, Gary W. Gill, Daniel F. Kurtycz, Celeste N. Powers, Nancy A. Young
Journal: Journal of Clinical Oncology (2005)
Significant Mitral Regurgitation Left Untreated at the Time of Aortic Valve Replacement
Authors: Luis Nombela-Franco, Henrique Barbosa Ribeiro, Marina Urena, Ricardo Allende, Ignacio Amat-Santos, Robert DeLarochellière, Eric Dumont, Daniel Doyle, Hugo DeLarochellière, Jerôme Laflamme, Louis Laflamme, Eulogio García, Carlos Macaya, Pilar Jiménez-Quevedo, Mélanie Côté, Sebastien Bergeron, Jonathan Beaudoin, Philippe Pibarot, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2014)
Comparison of Cetuximab and Bevacizumab as First-Line Treatment in KRAS Wild Type Advanced Colorectal Cancer Patients: A Retrospective Analysis
Authors: Zhang Qian, Yau Thomas, Leung Roland, Wong Hilda, Chiu Joanne, Chu Kin Wah, Poon Jensen, Kwong Yok Lam
Journal: Annals of Oncology (2014)
THE LETHAL EFFECT OF RELATIVE HUMIDITY ON AIR-BORNE BACTERIA
Authors: Edward W. Dunklin, Theodore T. Puck
Journal: The Journal of Experimental Medicine (1948)

The viability of pneumococcus, Type I, sprayed into the atmosphere from a liquid suspension was measured as a function of the relative humidity. When broth, saliva, or 0.5 per cent saline solution is employed as the suspending medium, a very high mortality rate is observed at relative humidities in the vicinity of 50 per cent. However, at humidities above or below this value the microorganisms survive for long periods. Measurement of the rate of settling of droplets employed in these experiments demonstrated that the disappearance of microorganisms from the air is a true lethal process, rather than a manifestation of aerosol collision processes. When a saline-free fluid was used, the sharp peak in death rate at intermediate relative humidities disappears. The lethal effect of intermediate relative humidities on pneumococci atomized from a saline-containing suspension is increased when the particle size of the atomized droplets is increased or when the temperature is raised. Cultures of hemolytic streptococcus group C and staphylococcus sprayed from a broth medium exhibit the same general survival pattern as a function of relative humidity although the mortality rates are smaller than that of the pneumococcus. These effects can be explained by assuming the existence of a critical degree of cellular dehydration at which microorganisms become much more sensitive to toxic agents than in states where either more or less water is bound to the cell. The results presented here may be significant in elucidating certain aspects of the epidemiology of air-borne infections.
Progress and controversies: Radiation therapy for invasive breast cancer
Authors: Reshma Jagsi
Journal: CA A Cancer Journal for Clinicians (2013)

Answer questions and earn CME/CNE Radiation therapy is a critical component of the multidisciplinary management of invasive breast cancer. In appropriately selected patients, radiation not only improves local control, sparing patients the morbidity and distress of local recurrence, but it also improves survival by preventing seeding and reseeding of distant metastases from persistent reservoirs of locoregional disease. In recent years, considerable progress has been made toward improving our ability to select patients most likely to benefit from radiotherapy and to administer treatment in ways that maximize clinical benefit while minimizing toxicity and burden. This article reviews the role of radiation therapy in invasive breast cancer management, both after breast‐conserving surgery and after mastectomy. It focuses particularly on emerging evidence that helps to define the clinical situations in which radiotherapy is indicated, the appropriate targets of treatment, and optimal approaches for minimizing both the toxicity and the burden of treatment, all in the context of the evolving surgical and systemic management of this common disease. It includes a discussion of new approaches in breast cancer radiotherapy, including hypofractionation and intensity modulation, as well as a discussion of promising avenues for future research. CA Cancer J Clin 2014;64:135–152. © 2013 American Cancer Society .
Chromogranin A Regulates Renal Function by Triggering Weibel–Palade Body Exocytosis
Authors: Yuqing Chen, Manjula Mahata, Fangwen Rao, Srikrishna Khandrika, Maite Courel, Maple M. Fung, Kuixing Zhang, Mats Stridsberg, Michael G. Ziegler, Bruce A. Hamilton, Michael S. Lipkowitz, Laurent Taupenot, Caroline Nievergelt, Sushil K. Mahata, Daniel T. O'Connor
Journal: Journal of the American Society of Nephrology (2009)

Chromogranin A (CHGA), a protein released from secretory granules of chromaffin cells and sympathetic nerves, triggers endothelin-1 release from endothelial cells. CHGA polymorphisms associate with an increased risk for ESRD, but whether altered CHGA-endothelium interactions may explain this association is unknown. Here, CHGA led to the release of endothelin-1 and Weibel-Palade body exocytosis in cultured human umbilical vein endothelial cells. In addition, CHGA triggered secretion of endothelin-1 from glomerular endothelial cells and TGF-beta1 from mesangial cells cocultured with glomerular endothelial cells. In humans, plasma CHGA correlated positively with endothelin-1 and negatively with GFR. GFR was highly heritable in twin pairs, and common promoter haplotypes of CHGA predicted GFR. In patients with progressive hypertensive renal disease, a CHGA haplotype predicted rate of GFR decline. In conclusion, these data suggest that CHGA acts through the glomerular endothelium to regulate renal function.
Neurocognitive function in patients with recurrent glioblastoma treated with bevacizumab
Authors: J. S. Wefel, T. Cloughesy, J. L. Zazzali, M. Zheng, M. Prados, P. Y. Wen, T. Mikkelsen, D. Schiff, L. E. Abrey, W. K. A. Yung, N. Paleologos, M. K. Nicholas, R. Jensen, J. Vredenburgh, A. Das, H. S. Friedman
Journal: Neuro-Oncology (2011)

Neurocognitive decline is a frequent adverse effect of glioblastoma. Antitumor therapies that are efficacious, as measured by traditional endpoints such as objective response (OR) and progression-free survival (PFS), and have beneficial effects on neurocognitive function (NCF) are of clinical benefit to these patients. We evaluated neurocognitive changes across time in 167 patients with recurrent glioblastoma treated with bevacizumab-based therapy in BRAIN, a phase II, randomized, multicenter trial. All patients underwent MRI and neurocognitive testing at baseline and every 6 weeks thereafter. Memory, visuomotor scanning speed, and executive function were evaluated using the Hopkins Verbal Learning Test–Revised, the Trail Making Test, and the Controlled Oral Word Association test, respectively. NCF relative to baseline for patients with an OR, PFS >6 months, or disease progression was evaluated at time of OR, 24 weeks, and time of progression, respectively. For patients with an OR or PFS >6 months, median standardized test scores were examined from baseline to week 24. Most patients with an OR or PFS >6 months had poorer NCF performance compared to the general population at baseline and had improved or stable NCF at the time of response or at the 24-week assessment, respectively; most patients with progressive disease had neurocognitive decline at the time of progression. For patients with an OR or PFS >6 months, median standardized test scores were largely stable across the first 24 weeks on study. Neurocognitive testing was an objective, valid, and feasible method of monitoring NCF in patients with recurrent glioblastoma.
757-2 Angiotensin II Formation in the Intact Human Heart: Predominance of the Angiotensin Converting Enzyme Pathway
Authors: Lawrence S. Zisman, William T. Abraham, Glenn E. Meixell, Brian N. Vamvakias, Brian D. Lowes, Robert L. Roden, Robert A. Quaife, Bertron M. Groves, M. Benjamin Perryman, Michael R. Bristow
Journal: Journal of the American College of Cardiology (1995)
Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose
Authors: Thai M. Cao, Judith A. Shizuru, Ruby M. Wong, Kevin Sheehan, Ginna G. Laport, Keith E. Stockerl-Goldstein, Laura J. Johnston, Monic J. Stuart, F. Carl Grumet, Robert S. Negrin, Robert Lowsky
Journal: Blood (2004)
Simultaneous targeting of HCV replication and viral binding with a single lentiviral vector containing multiple RNA interference expression cassettes
Authors: Scot D. Henry, Pascal van der Wegen, Herold J. Metselaar, Hugo W. Tilanus, Bob J. Scholte, Luc J.W. van der Laan
Journal: Molecular Therapy (2006)

Chronic hepatitis C virus (HCV) infection has a major medical impact and current treatments are often unsuccessful. RNA interference represents a promising new approach to tackling this problem. The current study details the design and testing of self-inactivating lentiviral vectors (LV) delivering RNA interference to prevent HCV replication and infection. Vectors were constructed with single, double, and triple cassettes expressing short hairpin RNAs (shRNAs) simultaneously targeting two regions of the HCV 1b genome and the host cell receptor, CD81. The shRNAs directed against HCV IRES or NS5b regions were shown to be effective in inhibiting HCV replication in vitro (82 and 98%, respectively). No evidence of shRNA-related interferon production was observed. Vectors containing CD81 shRNA reduced cell surface expression up to 83% and reduced cell binding of HCV surface protein E2 up to 82% while not affecting levels of unrelated surface protein (Ber-EP4) or HCV replication. Double or triple shRNA vectors were independently effective in simultaneously reducing HCV replication, CD81 expression, and E2 binding. This study demonstrates lentiviral delivery of multiple shRNA, inhibiting HCV in a specific, IFN-independent, manner. The targeting of multiple viral and host cell elements simultaneously by RNAi could increase the potency of antiviral gene therapies.
A Brain Protein–Centered View of H+ Buffering
Authors: Manjula Gowrishankar, Kamel S. Kamel, Mitchell L. Halperin
Journal: Journal of the American Society of Nephrology (2007)

In the traditional approach to buffering of H(+) during metabolic acidosis, the sole focus is on lowering the H(+) concentration, but this overlooks several important points. First, increased binding of H(+) to proteins changes their charge, shape, and possibly function. Second, organs in which buffering of H(+) occurs is not assessed even though it would be advantageous to spare brain proteins in this process. Third, only the arterial and not the capillary PCO(2) of individual organs is considered. This article provides a "brain protein-centered" view, which leads to different conclusions concerning the way H(+) are removed physiologically.
Regulation of immune responses to protein therapeutics by transplacental induction of T cell tolerance
Authors: Nimesh Gupta, Slobodan Culina, Yann Meslier, Jordan Dimitrov, Christophe Arnoult, Sandrine Delignat, Bagirath Gangadharan, Maxime Lecerf, Sune Justesen, Valérie Gouilleux-Gruart, Benoit L. Salomon, David W. Scott, Srinivas V. Kaveri, Roberto Mallone, Sébastien Lacroix-Desmazes
Journal: Science Translational Medicine (2015)

Transplacental modulation of T cell repertoire during immune ontogeny leads to antigen-specific immune tolerance to an immunogenic protein therapeutic.
The theoretical indispensability of concepts
Authors: Daniel A. Weiskopf
Journal: Behavioral and Brain Sciences (2010)

Machery denies the traditional view that concepts are constituents of thoughts, and he more provocatively argues that concepts should be eliminated from our best psychological taxonomy. I argue that the constituency view has much to recommend it (and is presupposed by much of his own theory), and that the evidence gives us grounds for pluralism, rather than eliminativism, about concepts.
Deprivation of arginine by recombinant human arginase in prostate cancer cells
Authors: Eddy C Hsueh, Stephanie M Knebel, Wai-Hung Lo, Yun-Chung Leung, Paul Ning-Man Cheng, Chung-Tsen Hsueh
Journal: Journal of Hematology & Oncology (2012)

Recombinant human arginase (rhArg) has been developed for arginine deprivation therapy in cancer, and is currently under clinical investigation. During pre-clinical evaluation, rhArg has exhibited significant anti-proliferative activity in cancer cells deficient in the expression of ornithine carbamoyl transferase (OCT). Interestingly, a variety of cancer cells such as melanoma and prostate cancer deficient in argininosuccinate synthetase (ASS) are sensitive to arginine deprivation by arginine deiminase. In this study, we investigated levels of gene expression of OCT and ASS, and the effects of rhArg in human prostate cancer cells: LNCaP (androgen-dependent), PC-3 and DU-145 (both androgen-independent).Quantitative real-time PCR showed minimal to absent gene expression of OCT, but ample expression of ASS expression in all 3 cell lines. Cell viability assay after 72-h exposure of rhArg showed all 3 lines had half maximal inhibitory concentration less than or equal to 0.02 U/ml. Addition of ornithine to cell culture media failed to rescue these cells from rhArg-mediated cytotoxicity.Decreased phosphorylation of 4E-BP1, a downstream effector of mammalian target of rapamycin (mTOR), was noted in DU-145 and PC-3 after exposure to rhArg. Moreover, there was no significant apoptosis induction after arginine deprivation by rhArg in all 3 prostate cancer cell lines.rhArg causes significant cytotoxicity in LNCaP, DU-145 and PC-3 prostate cancer cells which all demonstrate decreased OCT expression. Inhibition of mTOR manifested by hypophosphorylation of 4E-BP1 suggests autophagy is involved as alternative cell death mechanism. rhArg demonstrates a promising novel agent for prostate cancer treatment.