tbuckley/cabot-search huggingface dataset:
Dependence Receptors and Cancer: Addiction to Trophic Ligands
Authors: Benjamin Gibert, Patrick Mehlen
Journal: Cancer Research (2015)

Abstract Data accumulating over the last 20 years support the notion that some transmembrane receptors are activated not only by their respective ligands but also, differentially, by the withdrawal or absence of these same ligands. In this latter setting, these receptors actively trigger apoptosis. They have been dubbed dependence receptors because their expression confers a state of ligand dependence for survival on the expressing cells. Twenty of these receptors have been identified to date, and several have been shown to inhibit tumor progression by inducing apoptosis. As a corollary, these receptors, or their transduced death signals, are frequently silenced in cancer cells as a selective mechanism to prevent cell death, allowing invasion and metastasis. Drugs aimed at inducing programmed cell death in neoplastic cells by re-engaging the proapoptotic activity induced by unliganded dependence receptors are in late-stage preclinical tests, poised for clinical evaluation. This approach may offer novel opportunities for patient treatments. In this review, we discuss the implications of dependence receptors in limiting cancer progression and address the therapeutic perspectives brought to light by this paradigm. Cancer Res; 75(24); 5171–5. ©2015 AACR.
Hepatocyte Nuclear Factor 1, a Transcription Factor at the Crossroads of Glucose Homeostasis
Authors: MARCO PONTOGLIO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Hepatocyte nuclear factor 1 (HNF1) is a transcription factor involved in the regulation of a large set of hepatic genes, including albumin, β-fibrinogen, and α1-antitrypsin. HNF1 is expressed in the liver, digestive tract, pancreas, and kidney. Mice lacking HNF1 exhibit hepatic, pancreatic, and renal dysfunctions. HNF1-deficient mice fail to express the hepatic phenylalanine hydroxylase gene, giving rise to hyperphenylalaninemia. Renal proximal tubular reabsorption of glucose, phosphate, arginine, and other metabolites is affected, producing severe renal glucosuria, phosphaturia, and amino aciduria. Homozygous mutant mice also exhibit a dramatic insulin secretion defect. This dysfunction resembles that exhibited by patients with maturity-onset diabetes mellitus of the young type 3, who carry mutations in the human HNF1 gene in the heterozygous state. These data show that HNF1 is a major regulator of glucose homeostasis, regulating the expression of genes that are expressed in the liver, kidney, and pancreas.
Use of magnetic resonance targeting to steer ov-loaded cell-based therapies to tumor sites in vivo
Authors: Munitta Muthana, Aneurin Kennerley, Emer Murphy, Russell Hughes, Joe Conner, Fiona Wright, Mark Lythgoe, Jon Dobson, Jim Wild, Claire Lewis
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Despite considerable progress in the development of cell-based therapies, targeted delivery to specific tissues - particularly those deep in the body where direct injection is not possible - has been problematic. Here we show that tumour-conditioned macrophages infected with
Immunoregulation and genotype in colorectal cancer
Authors: Sarah E Church, Gabriela Bindea, Bernhard Mlecnik, Tessa Fredricksen, Jerome Galon
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Classical methods for determining malignant disease prognosis are based upon characterizing the morphology and location of tumor cells. While this analysis provides important information about a patient's disease it fails to capture the biological complexity of the tumor
A Phase III study (CheckMate 238) of adjuvant immunotherapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage IIIb/c or stage IV melanoma (MEL) in patients (pts) at high risk for recurrence
Authors: Jeffrey Weber, Jean-Jaques Grob, Kim A Margolin, Paolo A Ascierto, Mario Sznol, Patrick A Ott, Chantal Lejeune, Veerle de Pril, Mary M Ruisi, F Stephen Hodi
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts There is currently no consensus on the standard of care for pts with completely resected stage IIIB/C or stage IV MEL with no evidence of disease (NED) who are at high risk for recurrence. NIVO, a PD-1 immune checkpoint inhibitor, is approved in the United States, Europe, and
Increased Risk of Autism Spectrum Disorders in Children Born to Women With Systemic Lupus Erythematosus: Results From a Large Population‐Based Cohort
Authors: Évelyne Vinet, Christian A. Pineau, Ann E. Clarke, Susan Scott, Éric Fombonne, Lawrence Joseph, Robert W. Platt, Sasha Bernatsky
Journal: Arthritis & Rheumatology (2015)

In utero exposure to maternal antibodies and cytokines are potential risk factors for autism spectrum disorders (ASDs). The aim of this study was to determine whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of ASD compared to children born to mothers without SLE.The study population was derived from the Offspring of SLE Mothers Registry (OSLER), a large population-based cohort identified through healthcare databases in Quebec (1989-2009) comprising all women who had ≥1 hospitalization for a delivery (stillbirth or live birth) after SLE diagnosis. As general population controls, a randomly selected group of women without SLE was matched ≥4:1 to the mothers with SLE for age and year of delivery. Children born live to mothers with SLE and those born live to matched controls were identified, and a recorded diagnosis of ASD was ascertained for each child. Multivariate analyses were performed to adjust for parents' demographic characteristics, sex, birth order of the child, maternal comorbidities, and obstetric complications.In total, 509 women with SLE had 719 children, and 5,824 matched controls had 8,493 children. Children born to women with SLE were more frequently found to have a diagnosis of ASD compared to controls (frequency of recorded ASDs 1.4% [95% confidence interval (95% CI) 0.8-2.5] versus 0.6% [95% CI 0.5-0.8]), a difference of 0.8% (95% CI 0.1-1.9). The mean age at ASD diagnosis was younger in offspring of SLE mothers (mean 3.8 years, 95% CI 1.8-5.8) compared to offspring of controls (mean 5.7 years, 95% CI 4.9-6.5). In primary multivariate analysis, SLE offspring had a substantially increased risk of ASD compared to controls (odds ratio 2.19, 95% CI 1.09-4.39).Compared to children from the general population, children born to women with SLE have an increased risk of ASD, although, in absolute terms, it represents a rare outcome. These hypothesis-generating data provide direction for additional studies of maternal autoimmunity and ASD risk.
Comparison of the Efficacy of Filgrastim (Neupogen®) and Biosimilar Filgrastim (Leucostim®) in Patients with Chemotherapy-Induced Neutropenia: a Nationwide Observational Study
Authors: A. Sevinc, M. Ozkan, A. Ozet, F. Dane, B. Oksuzoglu, A. Isikdogan, F. Ozdemir, D. Uncu, M. Gumus, T. Evrensel, A. Yaren, O. Kara, S.B. Tekİn
Journal: Annals of Oncology (2014)
Abstract 2959: Pharmacological and Genetic Inhibition of Monoamine Oxidase A Prevents Enhanced Norepinephrine Catabolism and Heart Failure After Pressure Overload
Authors: Nina Kaludercic, Eiki Takimoto, Takahiro Nagayama, Edwin Lai, Djahida Bedja, Kevin Chen, Kathleen Gabrielson, Jean C Shih, Karel Pacak, David A Kass, Fabio Di Lisa, Nazareno Paolocci
Journal: Circulation (2009)
Interaction of Angiotensin II and Nitric Oxide in Isolated Perfused Afferent Arterioles of Mice
Authors: ANDREAS PATZAK, RALF MROWKA, EBERHARD STORCH, BERTHOLD HOCHER, PONTUS B. PERSSON
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The present study was performed to evaluate angiotensin II (Ang II)—nitric oxide (NO) interaction in afferent arterioles (Af) of wild-type mice and mice that are homozygous (-/-) for disruption of the endothelial NO synthase (eNOS) gene. Af were microperfused, and the dose responses were assessed for the NO precursor L-arginine (n = 4), NO inhibitor NG-nitro-L-arginine methyl ester (L-NAME, n = 5), L-NAME after pretreatment with L-arginine (n = 5), Ang II (n = 8), and Ang II after pretreatment with L-NAME (n = 7). Acute administration of L-arginine and L-NAME (both in doses from 10-6 to 10-3 mol/L) did not change arteriolar diameter. Moreover, pretreatment with L-arginine did not change the response to L-NAME. However, Ang II, applied in doses of 10-12, 10-10, 10-8, and 10-6 mol/L, significantly reduced the lumen to 66.5 ± 7.0% and 62.2 ± 8.0% at 10-8 and 10-6 mol/L Ang II, respectively. The contraction was augmented after L-NAME pretreatment (19.5 ± 13.6% and 25.5 ± 10.2% at 10-8 and 10-6 mol/L Ang II, respectively). In eNOS (-/-) mice (n = 8), the response to Ang II also was enhanced (9.1 ± 6.0% and 11.2 ± 8.2% at 10-8 and 10-6 mol/L Ang II, respectively). Female mice did not differ from male mice in their reactivity to Ang II (n = 9) and Ang II + L-NAME pretreatment (n = 11). The study shows that (1) it is feasible to microperfuse mouse Af, (2) the basal production of endothelial NO is very low and not inducible by L-arginine in Af of mice, and (3) a counteracting effect of NO is initiated by Ang II. High Ang II sensitivity in eNOS (-/-) mice underscores the considerable role of endothelial-derived NO to balance Ang II vasoconstriction in Af.
Spatiotemporally photoradiation-controlled intratumoral depot for combination of brachytherapy and photodynamic therapy for solid tumor
Authors: Ratul Mukerji, Jeffrey Schaal, Xinghai Li, Jayanta Bhattacharyya, Daisuke Asai, Michael R. Zalutsky, Ashutosh Chilkoti, Wenge Liu
Journal: Biomaterials (2015)
Influence of Donor Factors on Early Function of Graft Kidneys
Authors: DEEPIKA SURI, TIMOTHY W. MEYER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Factors which influence graft function can be divided into donor factors that affect both kidneys from the same donor equally and postdonor factors that affect each kidney individually. This study assessed the influence of donor factors on graft function early after transplantation. Sixty-one donors who provided kidneys that were transplanted locally into two separate recipients were identified. Recipient creatinine clearance values were estimated from serum creatinine concentrations using a computer model. Pairwise ANOVA showed that donor factors accounted for 35 to 45% of the variation in recipient creatinine clearance from 2 d to 2 wk posttransplantation. Although donor factors had a large aggregate effect during this period, individual factors that influenced graft function could not be identified from analysis of donor medical records. At 6 mo after transplantation, the effect of donor factors on graft function was no longer discernible. These results show that the condition of the donor exerts an important influence on graft function early after transplantation. More detailed study is required to identify individual factors that contribute to this effect.
Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study
Authors: Rengaswamy Sankaranarayanan, Priya Ramesh Prabhu, Michael Pawlita, Tarik Gheit, Neerja Bhatla, Richard Muwonge, Bhagwan M Nene, Pulikottil Okuru Esmy, Smita Joshi, Usha Rani Reddy Poli, Parimal Jivarajani, Yogesh Verma, Eric Zomawia, Maqsood Siddiqi, Surendra S Shastri, Kasturi Jayant, Sylla G Malvi, Eric Lucas, Angelika Michel, Julia Butt, Janki Mohan Babu Vijayamma, Subha Sankaran, Thiraviam Pillai Rameshwari Ammal Kannan, Rintu Varghese, Uma Divate, Shila Thomas, Geeta Joshi, Martina Willhauck-Fleckenstein, Tim Waterboer, Martin Müller, Peter Sehr, Sanjay Hingmire, Alka Kriplani, Gauravi Mishra, Sharmila Pimple, Radhika Jadhav, Catherine Sauvaget, Massimo Tommasino, Madhavan Radhakrishna Pillai
Journal: The Lancet Oncology (2015)

An increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study.
Suitability of Patients with Autosomal Dominant Polycystic Kidney Disease for Renal Transcatheter Arterial Embolization
Authors: Tatsuya Suwabe, Yoshifumi Ubara, Koki Mise, Toshiharu Ueno, Keiichi Sumida, Masayuki Yamanouchi, Noriko Hayami, Junichi Hoshino, Masahiro Kawada, Aya Imafuku, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Kenmei Takaichi
Journal: Journal of the American Society of Nephrology (2015)

In patients with autosomal dominant polycystic kidney disease (ADPKD), massive renal enlargement is a serious problem. Renal transcatheter arterial embolization (TAE) can reduce renal volume (RV), but effectiveness varies widely, and the reasons remain unclear. We investigated factors affecting renal volume reduction rate (RVRR) after renal TAE in all 449 patients with ADPKD who received renal TAE at Toranomon Hospital from January of 2006 to July of 2013, including 228 men and 221 women (mean age =57.0±9.1 years old). One year after renal TAE, the RVRR ranged from 3.9% to 84.8%, and the least squares mean RVRR calculated using a linear mixed model was 45.5% (95% confidence interval [95% CI], 44.2% to 46.8%). Multivariate analysis using the linear mixed model revealed that RVRR was affected by the presence of large cysts with wall thickening (regression coefficient [RC], −6.10; 95% CI, −9.04 to −3.16; P &lt;0.001), age (RC, −0.82; 95% CI, −1.03 to −0.60; P &lt;0.001), dialysis duration (RC, −0.10; 95% CI, −0.18 to −0.03; P &lt;0.01), systolic BP (RC, 0.39; 95% CI, 0.19 to 0.59; P &lt;0.001), and the number of microcoils used for renal TAE (RC, 1.35; 95% CI, 0.83 to 1.86; P &lt;0.001). Significantly more microcoils were needed to achieve renal TAE in patients with younger age and shorter dialysis duration. In conclusion, cyst wall thickening had an important effect on cyst volume reduction. Renal TAE was more effective in patients who were younger, had shorter dialysis duration, or had hypertension, parameters that might associate with cyst wall stiffness and renal artery blood flow.
Targeting acute myeloid leukemia with a small molecule inhibitor of the Myb/p300 interaction
Authors: Sagar Uttarkar, Emilie Dassé, Anna Coulibaly, Simone Steinmann, Anke Jakobs, Caroline Schomburg, Amke Trentmann, Joachim Jose, Peter Schlenke, Wolfgang E. Berdel, Thomas J. Schmidt, Carsten Müller-Tidow, Jon Frampton, Karl-Heinz Klempnauer
Journal: Blood (2015)
Low-Molecular Weight Proteins in End-Stage Renal Disease
Authors: William R. Clark, Dayong Gao
Journal: Journal of the American Society of Nephrology (2002)

Low-molecular-weight proteins (LMWP) are now recognized as a distinct class of uremic toxins, and numerous compounds in this category have been identified. Dr. Henderson has spent much of his career investigating ways to enhance the removal of intermediate- and large-sized uremic retention molecules. As LMWP clearly fall under this category, it is fitting to provide a review of several aspects of this molecular class. Normal renal metabolism of LMWP is discussed along with the changes that occur during chronic renal insufficiency. The effect of end-stage renal disease on plasma LMWP concentrations is assessed. As examples of the potential uremic toxicity of this molecular class, leptin, adrenomedullin, and the compounds associated with increased susceptibility to infection are highlighted. Finally, an overview of LMWP removal mechanisms for both hemodialysis and the convective therapies is provided.
Effects of evidence-based prevention training on neuromuscular and biomechanical risk factors for ACL injury in adolescent female athletes: a randomised controlled trial
Authors: Mette K Zebis, Lars L Andersen, Mikkel Brandt, Grethe Myklebust, Jesper Bencke, Hanne Bloch Lauridsen, Thomas Bandholm, Kristian Thorborg, Per Hölmich, Per Aagaard
Journal: British Journal of Sports Medicine (2015)

Background Adolescent female football and handball players are among the athletes with the highest risk of sustaining anterior cruciate ligament (ACL) injuries. Aim This study evaluated the effects of evidence-based lower extremity injury prevention training on neuromuscular and biomechanical risk factors for non-contact ACL injury. Methods 40 adolescent female football and handball players (15–16 years) were randomly allocated to a control group (CON, n=20) or neuromuscular training group (NMT, n=20). The NMT group performed an injury prevention programme as a warm-up before their usual training 3 times weekly for 12 weeks. The CON group completed their regular warm-up exercise programme before training. Players were tested while performing a side cutting movement at baseline and 12-week follow-up, using surface electromyography (EMG) and three-dimensional movement analysis. We calculated: (1) EMG amplitude from vastus lateralis (VL), semitendinosus (ST) and biceps femoris 10 ms prior to initial contact (IC) normalised to peak EMG amplitude recorded during maximal voluntary isometric contraction and (2) VL-ST EMG preactivity difference during the 10 ms prior to foot contact (primary outcome). We measured maximal knee joint valgus moment and knee valgus angle at IC. Results There was a difference between groups at follow-up in VL-ST preactivity (43% between-group difference; 95% CI 32% to 55%). No between-group differences were observed for kinematic and kinetic variables. Conclusions A 12-week injury prevention programme in addition to training and match play in adolescent females altered the pattern of agonist-antagonist muscle preactivity during side cutting. This may represent a more ACL-protective motor strategy.
A possible molecular basis of natriuresis during ischemic-reperfusion injury in the kidney.
Authors: Z Wang, H Rabb, M Haq, G E Shull, M Soleimani
Journal: Journal of the American Society of Nephrology (1998)

Ischemic renal injury is associated with increased fractional excretion of sodium, suggesting a Na+ reabsorption deficiency in renal tubules. To determine whether alterations in expression of the major Na+ transporter genes might contribute to the natriuresis that follows ischemic acute renal failure, the expression of these genes was analyzed in renal cortex and medulla after ischemic-reperfusion injury. Rats were subjected to 30 min of renal pedicle clamping and then sacrificed at 12, 24, or 48 h after reperfusion. Serum creatinine increased significantly at 12 and 24 h, indicative of acute renal failure, but decreased substantially by 48 h. mRNA levels for the NHE-3 Na/H exchanger of the proximal tubule, the apical Na-K-2Cl cotransporter of the thick ascending limb of Henle, the Na-Cl cotransporter of the distal convoluted tubule, the epithelial Na+ channel of the collecting duct, and the basolateral Na(+)-K(+)-ATPase were measured by Northern hybridization. NHE-3 mRNA decreased by approximately 75% at 12 h and remained suppressed at 24 and 48 h after reperfusion. Na-K-2Cl cotransporter mRNA decreased by approximately 88% at 12 h and remained suppressed at 24 and 48 h. Na-Cl cotransporter mRNA remained unchanged at 12 h, decreased by approximately 60% at 24 h, and returned to almost control levels at 48 h. mRNA levels for sodium channels (beta subunit) remained unchanged. Na(+)-K(+)-ATPase mRNA in the medulla decreased by approximately 35 to 40% at 12 and 24 h and by 70% at 48 h, whereas in cortex it decreased by only < 15% at 12 or 48 h after reperfusion. These results suggest that sharp reductions in expression of the NHE-3 Na/H exchanger and the apical Na-K-2Cl cotransporter are major factors in the natriuresis/diuresis that is one of the hallmarks of ischemic acute renal failure. Lasting suppression of these transporters, despite improvement in renal function, could contribute to the deranged NaCl and water excretion that often leads to volume depletion during recovery from ischemic acute renal failure.
Oral contraceptives and migraine headaches. [Answer to question of Dale B. Sherrod].
Authors: Archer Df
Journal: JAMA (1986)

An obstetrician-gynecologist (Dr. Archer) and a neurologist (Dr. Chesson) answered that a woman with the diagnosis of migraine headaches could use a combination oral contraceptive (OC) although they are not usually prescribed for women who have frequent severe migraine headaches.  Migraine headaches have been found to occur more frequently in postmenarchal women compared with men in a ratio of 80:20 suggesting that there may be a hormonal etiology.  The occurrence of migraine headaches has been related to the menstrual cycle with the reported occurrence of menstrually related headaches ranging from 10%-40%.  It should be noted that women using OCs have been found to have an increased occurrence of migraine headaches at the midpoint of an OC cycle.  The reason for this is unclear and is not consistent with the concept that the migraine is triggered by steroid withdrawal.  Several investigators have reported that OCs definitely appear to increase the frequency of headaches and often cause or initiate migraine headache in previously asymptomatic individuals.  However each of the reports indicating a relationship between OCs and the frequency of migraine headache is derived from a biased population representing either a headache clinic a neurological service or responses to a specific advertisement for migraine sufferers.  The use of OCs has also been associated with clinical improvement in both the severity and the frequency of migraine headaches.  Several epidemiologic studies do not document an increased incidence of migraine headache in OC users.  This could be due to the fact that physicians usually do not prescribe OCs to women who have migraine headaches.  Migraine headaches are associated with a significantly increased risk of both thrombotic and hemorrhagic strokes in women are not using OCs.  It is known that strokes or cerebrovascular accidents can occur at any age and OCs are associated with an increased risk of stroke.  There does not appear to be any significant increase in the risk of either thrombotic or hemorrhagic stroke in women who complained of migraine headaches and who also used OCs.  Therefore the medical literature does not conclusively demonstrate an increased frequency or severity of migraine headaches in women using OCs or an increased risk for stroke in women with migraine headaches who are using OCs.  However the risk of stroke in women who have migraine headaches does appear to be increased as compared with that of women who do not have migraine headaches.  (full text)
Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients
Authors: Xénia Cabagnols, Fabrizia Favale, Florence Pasquier, Kahia Messaoudi, Jean Philippe Defour, Jean Christophe Ianotto, Christophe Marzac, Jean Pierre Le Couédic, Nathalie Droin, Ilyas Chachoua, Remi Favier, M’boyba Khadija Diop, Valérie Ugo, Nicole Casadevall, Najet Debili, Hana Raslova, Christine Bellanné-Chantelot, Stefan N. Constantinescu, Olivier Bluteau, Isabelle Plo, William Vainchenker
Journal: Blood (2015)