tbuckley/cabot-search huggingface dataset:
Molecular Pathways: Targeting the CXCR4–CXCL12 Axis—Untapped Potential in the Tumor Microenvironment
Authors: Stefania Scala
Journal: Clinical Cancer Research (2015)

Evidence suggests that the CXC-chemokine receptor-4 pathway plays a role in cancer cell homing and metastasis, and thus represents a potential target for cancer therapy. The homeostatic microenvironment chemokine CXCL12 binds the CXCR4 and CXCR7 receptors, activating divergent signals on multiple pathways, such as ERK1/2, p38, SAPK/JNK, AKT, mTOR, and the Bruton tyrosine kinase (BTK). An activating mutation in CXCR4 is responsible for a rare disease, WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), and dominant CXCR4 mutations have also been reported in Waldenstrom macroglobulinemia. The CXCR4-CXCL12 axis regulates the hematopoietic stem cell niche--a property that has led to the approval of the CXCR4 antagonist plerixafor (AMD3100) for mobilization of hematopoietic precursors. In preclinical models, plerixafor has shown antimetastatic potential in vivo, offering proof of concept. Other antagonists are in preclinical and clinical development. Recent evidence demonstrates that inhibiting CXCR4 signaling restores sensitivity to CTLA-4 and PD-1 checkpoint inhibitors, creating a new line for investigation. Targeting the CXCR4-CXCL12 axis thus offers the possibility of affecting CXCR4-expressing primary tumor cells, modulating the immune response, or synergizing with other targeted anticancer therapies.
Neurobiology of Pavlovian Fear Conditioning
Authors: Stephen Maren
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Learning the relationships between aversive events and the environmental stimuli that predict such events is essential to the survival of organisms throughout the animal kingdom. Pavlovian fear conditioning is an exemplar of this form of learning that is exhibited by both rats and humans. Recent years have seen an incredible surge in interest in the neurobiology of fear conditioning. Neural circuits underlying fear conditioning have been mapped, synaptic plasticity in these circuits has been identified, and biochemical and genetic manipulations are beginning to unravel the molecular machinery responsible for the storage of fear memories. These advances represent an important step in understanding the neural substrates of a rapidly acquired and adaptive form of associative learning and memory in mammals.
Safety and tolerability of a novel inhaled GATA3 mRNA targeting DNAzyme in patients with TH2-driven asthma
Authors: Ursula Homburg, Harald Renz, Wolfgang Timmer, Jens M. Hohlfeld, Friedeborg Seitz, Katrin Lüer, Alexandra Mayer, Anja Wacker, Oliver Schmidt, Jens Kuhlmann, Agnieszka Turowska, Julia Roller, Klaus Kutz, Gerhard Schlüter, Norbert Krug, Holger Garn
Journal: Journal of Allergy and Clinical Immunology (2015)
New functions for the aryl hydrocarbon receptor
Authors: D A Brenner
Journal: Hepatology (1996)

hepatitis C virus RNA sequences by polymerase chain reaction are located in the regulatory regions of genes and rein fixed liver tissue.Mod Pathol 1992;5:501-504.sponsible for the induction of these genes by dioxin 25.Bresters D, Schipper MEI, Reesink HW, Boeser-Nunnink BDM, and other halogenated aromatic hydrocarbons.Dioxin Cuypers HTM.The duration of fixation influences the yield of induces the genes that encode the drug metabolizing HCV cDNA-PCR products from formalin-fixed, paraffin-embedded liver tissue.J Med Virol 1994;48:267-272.enzymes cytochrome P451A1 (Aryl hydrocarbon hydroxylase), CYP1A2, and CYP1B1.These drug metabolizing enzymes are both induced by dioxin and also NEW FUNCTIONS FOR THE ARYL metabolize it, leading to highly reactive carcinogenic HYDROCARBON RECEPTOR and mutagenic metabolites.However, these enzymes Fernandez-Salguero P, Pineau T, Hilbert DM, do not appear to directly mediate the toxic effects of McPhail T, Lee SST, Kimura S, Nebert DW, et al.Imdioxin.Other genes that are also responsive to dioxin mune system impairment and hepatic fibrosis in mice include glutathione S-transferase-YA, aldehyde-dehylacking the dioxin-binding Ah receptor
Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements.
Authors: E Pizzichini, M M Pizzichini, A Efthimiadis, S Evans, M M Morris, D Squillace, G J Gleich, J Dolovich, F E Hargreave
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Methods to examine sputum for indices of airway inflammation are evolving. We have examined the repeatability and the validity of an improved method to measure sputum cells and fluid-phase eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), albumin, fibrinogen, tryptase, and interleukin-5 (IL-5). Sputum was induced with hypertonic saline twice within 6 d in 10 healthy subjects, 19 stable asthmatics, and 10 smokers with nonobstructive bronchitis. The method included the processing of freshly expectorated sputum separated from saliva, treatment with a fixed proportion of dithiothreitol 0.1% followed by Dulbecco's phosphate-buffered saline, making cytospins, and collecting the supernatant. The reproducibility of measurements, calculated by the intraclass correlation coefficient, was high for all indices measured with the exception of total cell counts and proportion of lymphocytes. Asthmatics, in comparison with healthy subjects and smokers with bronchitis, had a higher proportion of sputum eosinophils (median percent 5.2 versus 0.5 and 0.3), metachromatic cells (0.3 versus 0.07 and 0.08), ECP (1,040 micrograms/L versus 288 and 352), MBP (1,176 micrograms/L versus 304 and 160), and EDN (1,512 micrograms/L versus 448 and 272). Asthmatics differed from healthy subjects, but not from smokers with bronchitis, in the proportion of neutrophils (46.9% versus 24.1%), albumin (704 versus 288 micrograms/mL), and fibrinogen (2,080 versus 440 ng/mL). Smokers with bronchitis showed a trend for a higher neutrophil count and levels of albumin and fibrinogen than healthy subjects. The proportion of sputum eosinophils correlated positively with ECP, MBP, EDN, albumin and fibrinogen levels, and metachromatic cell counts correlated with tryptase. In asthmatics, IL-5 correlated with eosinophil counts. There was a significant negative correlation between sputum indices and expiratory flows and methacholine PC20. Thus, the methods of measuring cell and fluid phase markers in induced sputum used in this study are reproducible and valid. They can therefore be used to reliably measure these indices of airway inflammation.
Interleukin-6, Cortisol, and Depressive Symptoms in Ovarian Cancer Patients
Authors: Susan K. Lutgendorf, Aliza Z. Weinrib, Frank Penedo, Daniel Russell, Koen DeGeest, Erin S. Costanzo, Patrick J. Henderson, Sandra E. Sephton, Nicolas Rohleder, Joseph A. Lucci, Steven Cole, Anil K. Sood, David M. Lubaroff
Journal: Journal of Clinical Oncology (2008)

Inflammatory processes have been implicated in the pathogenesis of both depression and cancer. Links between depressive symptoms, interleukin-6 (IL-6), and cortisol dysregulation have been demonstrated in cancer patients, but vegetative versus affective components of depression have been minimally examined. The objective of the current study was to examine associations between IL-6, diurnal cortisol rhythms, and facets of depression in epithelial ovarian cancer patients.Patients awaiting surgery for a pelvic mass suspected for ovarian cancer completed questionnaires, collected salivary samples for 3 days presurgery, and gave a presurgical blood sample. Ascites was obtained during surgery. IL-6 was measured by enzyme-linked immunosorbent assay and cortisol by a chemiluminescence immunoassay. The final sample included 112 invasive ovarian cancer patients (86 advanced stage, 26 early stage) and 25 patients with tumors of low malignant potential (LMP).Advanced-stage ovarian cancer patients demonstrated elevations in vegetative and affective depressive symptoms, plasma IL-6, and the cortisol area under the curve (AUC) compared with patients with LMP tumors (all P < .05). Among invasive ovarian cancer patients, greater vegetative depression was related to elevated IL-6 in plasma (P = .008) and ascites (P = .024), but affective depression was unrelated to IL-6. Elevations in total depression (P = .026) and vegetative depression (P = .005) were also related to higher evening cortisol levels. Plasma IL-6 was related to greater afternoon and evening cortisol and cortisol AUC (all P values < .005).These results demonstrate significant relationships between IL-6, cortisol, and vegetative depression, and may have implications for treatment of depression in ovarian cancer patients.
Augmentation of intramembranous bone in rabbit calvaria using an occlusive barrier in combination with demineralized bone matrix (DBM): A pilot study
Authors: Víctor Beltrán, Wilfried Engelke, Ruth Prieto, Iván Valdivia-Gandur, Pablo Navarro, María Cristina Manzanares, Eduardo Borie, Ramón Fuentes
Journal: International Journal of Surgery (2014)
Complications of laparoscopic pelvic surgery: recognition, management and prevention
Authors: T. Li
Journal: Human Reproduction Update (1997)

Laparoscopic surgery has many advantages but it is not without complications. The complexity of the surgery significantly influences the complication rate. Laparoscopic surgeons ought to be aware of the possible complications and how they could be prevented, recognized without delay, and managed safely and efficiently. Important complications include injuries to the vessels, bowel and urinary tract. Incisional hernia ought to be reduced by careful closure of the fascia whenever a trocar > or =10 mm is used at the extraumbilical site. Gas embolism is a rare but potentially life threatening complication. Shoulder pain is a minor complication but is exceedingly common; it is less likely to occur if as much gas as possible is removed at the end of the operation while the patient is still in head down Trendelenburg position. Rare complications include pneumothorax, subcutaneous and pre-peritoneal emphysema, cardiac arrhythmia, nerve injury and venous thrombosis. Laparoscopic surgeons should also understand the principles of electrosurgery and how to avoid complications arising from the use of electrical energy including capacitative coupling, direct coupling and insulation failure.
Systematic comparison of MRI findings in pediatric ependymoblastoma with ependymoma and CNS primitive neuroectodermal tumor not otherwise specified
Authors: Johannes Nowak, Carolin Seidel, Torsten Pietsch, Balint Alkonyi, Taylor Laura Fuss, Carsten Friedrich, Katja von Hoff, Stefan Rutkowski, Monika Warmuth-Metz
Journal: Neuro-Oncology (2015)

Ependymoblastoma (EBL), ependymoma (EP), and primitive neuroectodermal tumors of the central nervous system not otherwise specified (CNS-PNET NOS) are pediatric brain tumors that can be differentiated by histopathology in the clinical setting. Recently, we described specific MRI features of EBL. In this study, we compare standardized MRI characteristics of EBL with EP and CNS-PNET NOS in a series comprising 22 patients in each group. All 66 centrally reviewed cases were obtained from the database of the German multicenter HIT trials. We systematically analyzed the initial MRI scans at diagnosis according to standardized criteria, and paired comparison was performed for EBL and EP, as well as for EBL and CNS-PNET NOS. We found differences between EBL and EP regarding age at diagnosis, MR signal intensity, tumor margin and surrounding edema, presence and size of cysts, and contrast enhancement pattern. Although MRI appearance of EBL shares many features with CNS-PNET NOS, we revealed significant differences in terms of age at diagnosis, tumor volume and localization, tumor margins, edema, and contrast enhancement. This is the first study that systematically compares multiple parameters of MRI in pediatric EBL with findings in EP and CNS-PNET NOS. Although a definite differentiation by means of MRI alone might not be feasible in the individual case, we identify significant differences between these tumor entities.
Collaboration on children's health has some way to go, experts warn
Authors: A. O'Dowd
Journal: BMJ (2009)

Progress on government plans to improve the health of children in England through better collaboration among various agencies is stalling because of cultural differences within central and local government, MPs have been warned.

Experts on children’s health have welcomed moves to boost collaboration across health and social care services for children but are sceptical about how easy this will be to achieve.

MPs on the parliamentary select committee on children, schools, and families held a one-off evidence session this week on the government’s child health strategy, Healthy Lives, Brighter Futures , which was …
Host Immunosurveillance Controls Tumor Growth via IFN Regulatory Factor-8–Dependent Mechanisms
Authors: Kristy M. Greeneltch, Monika Schneider, Seth M. Steinberg, David J. Liewehr, Trina J. Stewart, Kebin Liu, Scott I. Abrams
Journal: Cancer Research (2007)

IFN regulatory factor (IRF)-8 plays an important role in normal myelopoiesis. The loss of IRF-8 in myeloid cells results in a chronic myelogenous leukemia-like syndrome, suggesting that IRF-8 behaves as a tumor suppressor gene in certain hematopoietic malignancies. We have been investigating the molecular determinants of solid tumor progression, with an emphasis on apoptotic resistance. Recently, we showed that IRF-8 expression was directly correlated with Fas-mediated apoptosis, and inversely related to malignant phenotype. However, the functional role of IRF-8 in solid tumors is unresolved. We stably silenced IRF-8 expression via RNA interference in IRF-8-expressing mouse tumor cells, and evaluated them for changes in apoptotic phenotype and malignant behavior. Apoptosis induced by Fas engagement or irradiation was markedly reduced in IRF-8-deficient tumor cells, despite unaltered proliferation, cell surface Fas, or MHC class I expression. Moreover, in syngeneic immunocompetent mice, IRF-8-deficient tumor cells grew more aggressively than their control counterparts. However, in IFN-gamma- or Fas ligand-deficient mice, but not T cell-deficient mice, both control and IRF-8-deficient tumor populations grew similarly. Furthermore, both tumor populations grew similarly in mice with defects in innate immunity. Although subsequent studies precluded a role for natural killer cells, immunohistochemical analysis supported the involvement of macrophages. Overall, our findings show that IRF-8 expression in solid tumor cells is important for efficient host immunosurveillance and response to apoptotic stimuli. Therefore, IRF-8 down-regulation may represent a previously unrecognized tumor escape mechanism that facilitates tumor progression. Conversely, strategies aimed at up-regulating or restoring IRF-8 expression in neoplastic cells may improve therapeutic efficacy.
Antisense c-myc and Immunostimulatory Oligonucleotide Inhibition of Tumorigenesis in a Murine B-Cell Lymphoma Transplant Model
Authors: J. B. Smith, E. Wickstrom
Journal: JNCI Journal of the National Cancer Institute (1998)

Because the development of drug-resistant cells can lead to relapses in patients with lymphoma treated with chemotherapy, new approaches are needed for effective disease management, such as those targeting the c-MYC proto-oncogene with antisense oligonucleotides. Our goal was to investigate whether antisense c-myc oligonucleotides could prevent tumorigenesis in a B-cell lymphoma model.Immunocompetent mice received subcutaneous injections of tumor cells from a transgenic mouse model of Burkitt's lymphoma. For 7 consecutive days, beginning 1 day after tumor cell transplantation, the mice were given either a DNA phosphorothioate oligonucleotide complementary to c-myc codons 1-5 (myc6) or other c-myc-related oligonucleotides at a dose of 0.76 mg per day subcutaneously. Myc protein expression, normalized to beta-actin expression, was measured by western blotting of tumor and splenic proteins. To determine whether tumor inhibition by myc6 could be a result of B-cell activation, we compared the activity of myc6 with that of an immunostimulatory oligonucleotide, mcg.In comparison with control treatments (saline vehicle, scrambled-sequence oligonucleotide, or double-mismatch oligonucleotide), treatment with myc6 delayed tumor onset by 3 days, decreased total tumor mass at sacrifice (i.e., 17 days after tumor cell transplantation) by 40% +/- 16% (mean +/- standard error), and decreased the splenic Myc-to-actin ratio. Inhibition of tumors by myc6 and mcg (both of which share a dACGTT motif) was comparable. Administration of an oligonucleotide sequence complementary to c-myc codons 384-388 (myc55) delayed tumor onset by 5-6 days, decreased total tumor mass at sacrifice by 65% +/- 6%, and reduced the splenic Myc-to-actin ratio to below that produced by myc6. A 14-day treatment regimen of myc55 alternating with mcg completely inhibited tumor formation during the therapeutic schedule.A combined oligonucleotide regimen, based on antisense c-MYC and immunostimulatory oligonucleotides, should be investigated to increase the number and duration of complete remissions obtained after standard chemotherapy for B-cell lymphoma.
Quantifying digital vascular disease in patients with primary Raynaud's phenomenon and systemic sclerosis
Authors: A. L Herrick, S. Clark
Journal: Annals of the Rheumatic Diseases (1998)

In primary and secondary Raynaud’s phenomenon, measurement of activity or severity, or both, of the digital vascular disease is a major challenge. We need to identify objective measures of digital vascular disease that are helpful in predicting those patients with Raynaud’s who have underlying connective tissue disease, and to measure reliably digital vascular disease progression, and responses to treatment.

None of the various physiological measurement techniques used in the assessment of patients with primary or secondary Raynaud’s are ideal. In this review we outline these techniques, highlighting their applications and limitations. The discussion concentrates on the physiological assessment of patients with primary Raynaud’s phenomenon (PRP) and systemic sclerosis (SSc), but is also applicable to other connective tissue diseases. We have not included biochemical markers of vascular injury or measurement of tissue oxygen levels.

In PRP, episodic ischaemia in response to cold exposure or to emotional stimuli is entirely reversible: absence of tissue damage is a defining feature.1 In contrast, SSc may be associated with irreversible tissue damage with ulceration, scarring and sometimes gangrene, and structural change occurs in the vasculature.2 3 Indeed, SSc is probably primarily a disease of the vasculature, although it is not clear how this interrelates with collagen and other connective tissue matrix metabolism.4 5 

Assessment of digital vascular disease needs to take into account:

(a) Digital vasospasm. This is best assessed by dynamic testing with standard stimuli, such as a standard cold stress.

(b) Structural vascular disease. This may affect basal blood flow in addition to vascular responses to standard stimuli.

In the patient presenting with Raynaud’s phenomenon, we must assess both the microvasculature and the digital arteries. Different physiological measurement techniques may be used in combination, especially if investigators wish to examine both digital artery and microvascular flow.6 

On widefield capillaroscopy, …
Assessment of airflow limitation, airway inflammation, and symptoms during virus-induced wheezing episodes in 4- to 6-year-old children
Authors: George N. Konstantinou, Paraskevi Xepapadaki, Emmanuel Manousakis, Heidi Makrinioti, Kalliopi Kouloufakou-Gratsia, Photini Saxoni-Papageorgiou, Nikolaos G. Papadopoulos
Journal: Journal of Allergy and Clinical Immunology (2012)
Transcutaneous oxygen tension in patients with post-thrombolic leg ulcers: treatment with intermittent pneumatic compression
Authors: P. J KOLARI, K. PEKANMAKI, R. T POHJOLA
Journal: Cardiovascular Research (1988)

Journal Article Transcutaneous oxygen tension in patients with post-thrombolic leg ulcers: treatment with intermittent pneumatic compression Get access PERTTI J KOLARI, PERTTI J KOLARI **From the Department of Dermatology, Päijät-Häme Central Hospital, Lahti, Finland Search for other works by this author on: Oxford Academic PubMed Google Scholar KALLE PEKANMÄKI, KALLE PEKANMÄKI **From the Department of Dermatology, Päijät-Häme Central Hospital, Lahti, Finland Search for other works by this author on: Oxford Academic PubMed Google Scholar RISTO T POHJOLA RISTO T POHJOLA †From the Department of Physical Medicine and Rehabilitation, Päijät-Häme Central Hospital, Lahti, Finland Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 2, February 1988, Pages 138–141, https://doi.org/10.1093/cvr/22.2.138 Published: 01 February 1988 Article history Received: 18 March 1987 Accepted: 05 September 1987 Published: 01 February 1988
Tumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects
Authors: M. Hockel, P. Vaupel
Journal: JNCI Journal of the National Cancer Institute (2001)

Tissue hypoxia results from an inadequate supply of oxygen (O(2)) that compromises biologic functions. Evidence from experimental and clinical studies increasingly points to a fundamental role for hypoxia in solid tumors. Hypoxia in tumors is primarily a pathophysiologic consequence of structurally and functionally disturbed microcirculation and the deterioration of diffusion conditions. Tumor hypoxia appears to be strongly associated with tumor propagation, malignant progression, and resistance to therapy, and it has thus become a central issue in tumor physiology and cancer treatment. Biochemists and clinicians (as well as physiologists) define hypoxia differently; biochemists define it as O(2)-limited electron transport, and physiologists and clinicians define it as a state of reduced O(2) availability or decreased O(2) partial pressure that restricts or even abolishes functions of organs, tissues, or cells. Because malignant tumors no longer execute functions necessary for homeostasis (such as the production of adequate amounts of adenosine triphosphate), the physiology-based definitions of the term "hypoxia" are not necessarily valid for malignant tumors. Instead, alternative definitions based on clinical, biologic, and molecular effects that are observed at O(2) partial pressures below a critical level have to be applied.