tbuckley/cabot-search huggingface dataset:
Integrin-linked Kinase Controls Renal Branching Morphogenesis via Dual Specificity Phosphatase 8
Authors: Joanna Smeeton, Priya Dhir, Di Hu, Meghan M. Feeney, Lin Chen, Norman D. Rosenblum
Journal: Journal of the American Society of Nephrology (2015)

Integrin-linked kinase (ILK) is an intracellular scaffold protein with critical cell-specific functions in the embryonic and mature mammalian kidney. Previously, we demonstrated a requirement for Ilk during ureteric branching and cell cycle regulation in collecting duct cells in vivo . Although in vitro data indicate that ILK controls p38 mitogen-activated protein kinase (p38MAPK) activity, the contribution of ILK-p38MAPK signaling to branching morphogenesis in vivo is not defined. Here, we identified genes that are regulated by Ilk in ureteric cells using a whole-genome expression analysis of whole-kidney mRNA in mice with Ilk deficiency in the ureteric cell lineage. Six genes with expression in ureteric tip cells, including Wnt11 , were downregulated, whereas the expression of dual-specificity phosphatase 8 (DUSP8) was upregulated. Phosphorylation of p38MAPK was decreased in kidney tissue with Ilk deficiency, but no significant decrease in the phosphorylation of other intracellular effectors previously shown to control renal morphogenesis was observed. Pharmacologic inhibition of p38MAPK activity in murine inner medullary collecting duct 3 (mIMCD3) cells decreased expression of Wnt11 , Krt23 , and Slo4c1 . DUSP8 overexpression in mIMCD3 cells significantly inhibited p38MAPK activation and the expression of Wnt11 and Slo4c1. Adenovirus-mediated overexpression of DUSP8 in cultured embryonic murine kidneys decreased ureteric branching and p38MAPK activation. Together, these data demonstrate that Ilk controls branching morphogenesis by regulating the expression of DUSP8, which inhibits p38MAPK activity and decreases branching morphogenesis.
Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial
Authors: Andrea Wang-Gillam, Chung-Pin Li, György Bodoky, Andrew Dean, Yan-Shen Shan, Gayle Jameson, Teresa Macarulla, Kyung-Hun Lee, David Cunningham, Jean F Blanc, Richard A Hubner, Chang-Fang Chiu, Gilberto Schwartsmann, Jens T Siveke, Fadi Braiteh, Victor Moyo, Bruce Belanger, Navreet Dhindsa, Eliel Bayever, Daniel D Von Hoff, Li-Tzong Chen, Clarence Adoo, Thomas Anderson, Jamil Asselah, Alan Azambuja, Carolyn Bampton, Carlos Henrique Barrios, Tanios Bekaii-Saab, Melichar Bohuslav, David Chang, Jen-Shi Chen, Yeu-Chin Chen, Hye Jin Choi, Ik Joo Chung, Vincent Chung, Tibor Csoszi, Antonio Cubillo, Linda DeMarco, Maike de Wit, Tomislav Dragovich, William Edenfield, Luis Enrique Fein, Fábio Franke, Martin Fuchs, Vega Gonzales-Cruz, Alberto Gozza, Rivera Herrero Fernando, Rosario Iaffaioli, Jitka Jakesova, Zsuzsanna Kahan, Misagh Karimi, Jun Suk Kim, Ernesto Korbenfeld, Istvan Lang, Fa-Chyi Lee, Kuan-Der Lee, Lara Lipton, Wen Wee Ma, Laszlo Mangel, Raul Mena, Daniel Palmer, Shubham Pant, Joon Oh Park, Paolo Piacentini, Uwe Pelzer, Javier Gallego Plazas, Cooray Prasad, Kun-Ming Rau, Jean-Luc Raoul, Donald Richards, Paul Ross, Luis Schlittler, Martin Smakal, Vladimira Stahalova, Cora Sternberg, Thomas Seufferlein, Niall Tebbutt, Jeferson Jose Vinholes, Raymond Wadlow, Milkos Wenczl, Mark Wong
Journal: The Lancet (2015)
New kid on the block
Authors: Howard A. Rockman
Journal: Journal of Clinical Investigation (2015)

As Editor of the Journal of Clinical Investigation, I am pleased to announce the January 2016 launch of JCI Insight, which will publish well-executed, high-quality research across biomedicine that presents a focused yet insightful line of investigation. The new journal, published under an open-access model, represents an expansion of the American Society for Clinical Investigation’s longstanding commitment to disseminating preclinical, translational, and early-phase clinical research that has the potential to advance the practice of medicine. JCI Insight will be the second Society publication since the JCI was founded in 1924.
The role of tubular iron accumulation in the remnant kidney.
Authors: B J Nankivell, J Chen, R A Boadle, D C Harris
Journal: Journal of the American Society of Nephrology (1994)

Iron has been implicated in the pathophysiology of several models of acute and chronic renal disease. In this study, energy-dispersive x-ray spectrometry was used to quantify and localize iron in rat remnant kidneys (RK) and normal kidneys (NK) and to determine its pathophysiologic significance. Substantial iron accumulation occurred in proximal tubular cell secondary lysosomes of RK (P < 0.001 versus NK) and reached a plateau at 8 wk after partial nephrectomy. In NK, minor increases of iron also occurred with aging (P < 0.02). Proximal tubular iron accumulation correlated independently with protein excretion (r = 0.90) and impairment of GFR (r = 0.70) and was associated with tubular damage and phosphate accumulation (both P < 0.001). Iron nitrilotriacetate (1 mg/kg ip) increased tubular lysosomal iron accumulation and tubular damage (P < 0.001 versus nitrilotriacetate) in NK, comparable to levels seen in untreated RK, and increased cortical cytosolic malondialdehyde, consistent with reactive oxygen species generation. The iron chelator deferoxamine (30 mg/kg per day ip) significantly reduced iron accumulation and tubular damage in RK at 4 wk, compared with deferoxamine chelated to iron and untreated RK. These results suggest that filtered iron enters the remnant tubular lysosomes across the brush border membrane by endocytosis and may produce tubular damage in chronic renal disease by the generation of reactive oxygen species.
Moving Photodynamic Medicine Forward by Stimulating Collaboration Between the Laboratory and the Clinic
Authors: Patrick Ross
Journal: Journal of the National Comprehensive Cancer Network (2012)

Photodynamic therapy (PDT) is alive and well in the United States. Although many contemporary research scientists and clinicians still consider PDT a niche therapy, with little appeal in mainstream medicine, PDT is an approved treatment in oncology for airway malignancies, Barrett’s esophagus with high-grade dysplasia, and nonmelanoma skin cancer. In addition, PDT has been used in the laboratory and in some investigational clinical settings for high-grade gliomas, oral and laryngeal lesions, inoperable cholangiocarcinomas, and lung-sparing surgery for malignant pleural mesothelioma. To crystallize the wealth of preclinical and clinical experiences with PDT in oncology and to explore potential emerging indications and refinements in technique, various colleagues from both sides of the Atlantic joined me at the inaugural International Photodynamic Medicine Symposium at The Ohio State University Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute in Columbus, Ohio, on May 11 and 12, 2012. This collaborative think tank included clinicians in thoracic surgery, gastroenterology, dermatology, and hepatology, and immunologists, physicists, biochemists, and photobiologists. Speakers
IL15N72D superagonist/IL15Rα-Fc fusion complex (ALT-803) exhibits anti-metastatic activity in murine breast tumor model
Authors: Peter S Kim, Anna R Kwilas, Emily K Jeng, Hing C Wong, Jeffrey Schlom, James W Hodge
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Interleukin (IL)-15N72D-superagonist-complexed with IL15Rα-Fc fusion protein (IL15-SA/IL15Rα-Fc, also known as ALT-803) has been reported to have greater anti-myeloma activity, due to its increased in vivo half-life and unique tissue biodistribution, than native IL-15 alone in
Erratum to: Lyn is involved in CD24-induced ERK1/2 activation in colorectal cancer
Authors: Ning Su, Liang Peng, Bingqing Xia, Yingying Zhao, Angao Xu, Jing Wang, Xinying Wang, Bo Jiang
Journal: Molecular Cancer (2012)

Correction To further confirm that the inactivation of Lyn inhibited CD24-induced ERK1/2 activation, we submitted the results of another CD24siRNA (CD24siRNA-2) as the Additional file 1: Figure S2. After publication of the article [1] the authors noted that the wrong figure for Additional file 1: Figure S2 was submitted by mistake. The correct image was conducted in SW480 using CD24siRNA-2 (new Additional file 1: attached). The authors apologise for any inconvenience caused.
Ar and Cyp17A1 Copy Number Variations May Predict Clinical Outcome of Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone
Authors: V. Conteduca, S. Salvi, V. Casadio, S.L. Burgio, C. Menna, L. Rossi, E. Bianchi, E. Carretta, F. Fabbri, D. Callistri, W. Zoli, U. De Giorgi
Journal: Annals of Oncology (2014)
Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial
Authors: Rosalind A. Eeles, James P. Morden, Martin Gore, Janine Mansi, John Glees, Miklos Wenczl, Christopher Williams, Henry Kitchener, Richard Osborne, David Guthrie, Peter Harper, Judith M. Bliss
Journal: Journal of Clinical Oncology (2015)

Purpose To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Patients and Methods Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. Results A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. Conclusion These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life.
Septic Shock and Acute Lung Injury in Rabbits with Peritonitis
Authors: GUSTAVO MATUTE-BELLO, CHARLES W. FREVERT, OSAMU KAJIKAWA, SHAWN J. SKERRETT, RICHARD B. GOODMAN, DAVID R. PARK, THOMAS R. MARTIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The major goal of this study was to investigate the mechanisms that link the host response to a local infection in the peritoneal cavity with the development of sepsis and lung injury. Rabbits were infected by intraperitoneal inoculation of fibrin clots containing Escherichia coli at 108, 109, or 1010 cfu/clot. Physiologic, bacteriologic, and inflammatory responses were monitored, and the lungs were examined postmortem. At a dose of 108 cfu/clot the animals had resolving infection, and a dose of 109 cfu/clot resulted in persistent infection at 24 h, with minimal systemic manifestations. In contrast, inoculation of 1010 cfu/clot resulted in rapidly lethal local infection, with septic shock and lung injury. The onset of septic shock was associated with a paradoxical lack of identifiable polymorphonuclear leukocytes (PMN; neutrophils) in the peritoneal cavity. The absence of PMN in the peritoneum was due in part to lysis of intraperitoneal PMN, because the peritoneal fluids contained free myeloperoxidase and induced rapid death of normal rabbit PMN in vitro. Although most animals became bacteremic, only those with a severe systemic inflammation response developed lung injury. These data show that control of an infection in the first compartment in which bacteria enter the host is a critical determinant of the systemic response. Above a threshold dose of bacteria, failure of the local neutrophil response is a key mechanism associated with deleterious systemic responses. Bacteremia alone is not sufficient to cause lung injury. Lung injury occurs only in the setting of a severe systemic inflammatory response and an inadequate leukocyte response at the primary site of infection.
Comparative Benefits and Harms of Second-Generation Antidepressants for Treating Major Depressive Disorder
Authors: Gerald Gartlehner, Richard A. Hansen, Laura C. Morgan, Kylie Thaler, Linda Lux, Megan Van Noord, Ursula Mager, Patricia Thieda, Bradley N. Gaynes, Tania Wilkins, Michaela Strobelberger, Stacey Lloyd, Ursula Reichenpfader, Kathleen N. Lohr
Journal: Annals of Internal Medicine (2011)

This review compares the benefits and harms of second-generation antidepressants for treating major depressive disorder in adults. On the basis of 234 studies, no clinically relevant differences in...
Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar V alpha and V beta chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different.
Authors: F R Burns, X B Li, N Shen, H Offner, Y K Chou, A A Vandenbark, E Heber-Katz
Journal: The Journal of Experimental Medicine (1989)

Prospects for specific immune intervention in T cell-mediated autoimmune disease via anti-idiotypic regulation depend on the degree of diversity of the responder cell antigen receptor repertoire. A highly heterogenous response against self epitopes offers little chance for such regulation. We report here that the Lewis rat autoimmune disease experimental allergic encephalomyelitis, generally considered to be a model of human multiple sclerosis, is caused by T cells that use a limited set of TCR V genes. We have cloned the rat TCR alpha and beta chain cDNAs from the Lewis rat x mouse T cell hybridoma 510, which retains the rat specificity for the encephalitogenic determinant of myelin basic protein (MBP). Using Northern blot analysis of T cell RNA with the cloned V region probes, we have found a specific, and near perfect, correlation between expression of TCR message hybridizing to the V alpha 510 and VB510 probes and specificity for the encephalitogenic determinant of MBP in both T cell hybridomas and encephalitogenic T cell clones. This restricted V gene usage provides a basis for observed idiotypic regulation of auto-reactive T cells, and possible therapy for autoimmune disease. A curious and unexplained observation is that the Lewis rat V alpha/V beta combination that dominates the encephalitogenic response to the 68-88 peptide of MBP is precisely the same V alpha/V beta combination used by the B10.PL mouse response to the encephalitogenic response to the 1-9 peptide of MBP.
Safety and Immunogenicity of MAGE-A3 Cancer Immunotherapeutic with or without Adjuvant Chemotherapy in Patients with Resected Stage IB to III MAGE-A3-Positive Non-Small-Cell Lung Cancer
Authors: Jean-Louis Pujol, Johan F. Vansteenkiste, Tommaso Martino De Pas, Djordje Atanackovic, Martin Reck, Michiel Thomeer, Jean-Yves Douillard, Gianpiero Fasola, Vanessa Potter, Paul Taylor, Lionel Bosquée, Robert Scheubel, Silvija Jarnjak, Muriel Debois, Pedro de Sousa Alves, Jamila Louahed, Vincent G. Brichard, Frédéric F. Lehmann
Journal: Journal of Thoracic Oncology (2015)

IntroductionTo assess the safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with stage IB–III MAGE-A3-positive non–small-cell lung cancer (NSCLC) who were or were not undergoing standard cisplatin/vinorelbine chemotherapy.MethodsThis open, prospective, multicenter, parallel-group phase I study (NCT00455572) enrolled patients with resected (cohorts 1–3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3 immunotherapeutic (300 μg recombinant MAGE-A3 formulated with AS15) was administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after standard radiotherapy and/or chemotherapy (cohort 4).ResultsSixty-seven patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic. Grade 3/4 adverse events (AEs) were reported for 16 out of 19 (84%), 2 out of 18 (11%), 5 out of 18 (28%), and 1 out of 12 (8%) patients in cohorts 1, 2, 3, and 4, respectively. Many grade 3/4 AEs in cohort 1 (e.g., neutropenia) were typical of chemotherapy. Six patients, including three in cohort 1, reported study treatment–related grade 3/4 AEs (injection-site reactions or musculoskeletal/back pain, which resolved within 5 days). One patient (in cohort 4) died, but this and the other serious adverse events were not study treatment related. MAGE-A3-specific antibody responses to immunotherapy were induced in all patients evaluated in all cohorts. MAGE-A3-specific CD4+ T-cell responses to immunotherapy were detected in 4 out of 11 (36%), 4 out of 15 (27%), 2 out of 8 (25%), and 5 out of 6 (83%) evaluated patients in cohorts 1, 2, 3, and 4, respectively; and CD8+ T-cell responses were only detected in four patients.ConclusionIn resected and unresectable NSCLC patients and irrespective of whether standard chemotherapy was concurrent or not, MAGE-A3 immunotherapeutic is well tolerated and induces MAGE-A3-specific immune responses.
The treatment of stage IIIA Hodgkin's disease--total nodal irradiation versus combination chemotherapy: either or neither.
Authors: A M Oza, M Leahy, J Lim, W Gregory, A G Stansfeld, P F Wrigley, T A Lister
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.8.1514 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2072154 The treatment of stage IIIA Hodgkin's disease--total nodal irradiation versus combination chemotherapy: either or neither. A M OzaxA M OzaSearch for articles by this author , M LeahyxM LeahySearch for articles by this author , J LimxJ LimSearch for articles by this author , W GregoryxW GregorySearch for articles by this author , A G StansfeldxA G StansfeldSearch for articles by this author , P F WrigleyxP F WrigleySearch for articles by this author , T A ListerxT A ListerSearch for articles by this author Show More https://doi.org/10.1200/JCO.1991.9.8.1514 First Page PDF © 1991 by American Society of Clinical Oncology
Bosentan Therapy for Pulmonary Arterial Hypertension
Journal: New England Journal of Medicine (2002)

Endothelin, a peptide produced primarily by vascular endothelial cells, was discovered in 1980 and it was characterized as a powerful vasoconstrictor and mitogen for smooth muscle. Endothelin binds to two types of receptors, ETA and ETB. Activation of ETA and ETB receptors on smooth muscle cells mediates the vasoconstrictive and mitogenic effects of endothelin. In patients with pulmonary hypertension, endothelin plasma levels are elevated and the increase is correlated with right atrial pressure, pulmonary artery oxygen saturation and pulmonary vascular resistance. Bosentan is an oral active dual ETA and ETBreceptor antagonist. Bosentan therapy has improved symptoms, exercise capacity, hemodynamics, echocardiographic parameters and the outcome of patients with severe pulmonary hypertension. This review is focus on the role of bosentan therapy in pulmonary hypertension and the review of current literature.
Relationship Between Rest Metabolism and Performance Status in Cancer Patients: a Prospective Study in 161 Patients
Authors: C. Vazeille, J. Durand, N. Neveux, A. Cessot, P. Boudou-Rouquette, A. Jouinot, J. Alexandre, L. Cynober, F. Goldwasser
Journal: Annals of Oncology (2014)
Presynaptic Deletion of GIT Proteins Results in Increased Synaptic Strength at a Mammalian Central Synapse
Authors: Mónica S. Montesinos, Wei Dong, Kevin Goff, Brati Das, Debbie Guerrero-Given, Robert Schmalzigaug, Richard T. Premont, Rachel Satterfield, Naomi Kamasawa, Samuel M. Young
Journal: Neuron (2015)
Novel Immunosuppressive Approach Attenuates Severe Aplastic Anemia in Mouse Lymphocyte Infusion AA Models
Authors: Jessica Lorente, Divya Kannegenti, Brandon Theall, Lisandra Hernandez, Esha Vallabhaneni, Vesna Jurecic, Vineet Gupta, Becky Adkins, Roland Jurecic
Journal: Blood (2014)
A comprehensive study of genic variation in natural populations of Drosophila melanogaster. VII. Varying rates of genic divergence as revealed by two-dimensional electrophoresis.
Authors: S Thomas, R S Singh
Journal: Molecular Biology and Evolution (1992)

Four sibling species from the melanogaster subgroup (Drosophila melanogaster, D. simulans, D. sechellia, and D. mauritiana) were studied for genetic divergence, by high-resolution two-dimensional protein electrophoresis (2DE) coupled with ultrasensitive silver staining. A total of eight tissues from larval and adult developmental stages representing both gonadal (germ-line) and nongonadal (somatic) tissues were analyzed for protein divergence between species. Close to 400 polypeptides (protein spots) were scored from each tissue and species, and protein divergence was measured on the basis of qualitative differences (presence/absence) of protein spots in pairwise species comparisons. The observed levels of genic divergence varied among tissues and among species. When larval hemolymph proteins (which are known to be highly polymorphic) were excluded, there was no evidence to suggest that either the larval or adult-stage proteins, as a whole, are more diverged than the other; variation between different tissues rather than between developmental stages appears to be the most significant factor affecting genetic divergence between species. The reproductive tissue (testis and accessory gland) showed more divergence than did the nonreproductive tissue; D. melanogaster testis (from both larvae and adult males) showed the highest level of divergence. In view of the previous observation that D. simulans, D. mauritiana, and D. sechellia show similar but significantly less reproductive isolation from each other than from D. melanogaster, the present results suggest a correlation between the levels of reproductive-tract-protein divergence and the degree of reproductive isolation in these species.