tbuckley/cabot-search huggingface dataset:
A Phase II Pharmacodynamic Study of Preoperative Figitumumab in Patients with Localized Prostate Cancer
Authors: Kim N. Chi, Martin E. Gleave, Ladan Fazli, S. Larry Goldenberg, Alan So, Christian Kollmannsberger, Nevin Murray, Anna Tinker, Michael Pollak
Journal: Clinical Cancer Research (2012)

Activation of the insulin-like growth factor 1 receptor (IGF-IR) is implicated in prostate cancer development and progression. This study evaluated biologic and clinical effects of figitumumab, a fully human monoclonal IGF-IR antibody, in patients with localized prostate cancer.Eligible patients received figitumumab 20 mg/kg intravenously every 3 weeks for 3 cycles followed by prostatectomy. The primary endpoint was IGF-IR expression inhibition as assessed by immunohistochemistry.Sixteen patients were accrued. Median age was 63 years, median prostate-specific antigen (PSA) was 7.2 μg/L (range, 2.5-35), clinical stage was T1 in four patients and T2 in 12 patients, Gleason score ≤ 7 or >7 in 15 and one patients. Two patients received only 1 cycle (patient choice and grade III hyperglycemia). A PSA decline from baseline of ≥ 25% and ≥ 50% occurred in 15 (94%) and 5 (31%) of patients. Mean figitumumab concentration was 350.4 μg/mL (range, 26.3-492.8) in plasma and 51.3 μg/g (range, 27.4-79.6) in prostate tissue. Compared with pretreatment biopsies, IGF-IR expression decreased in the prostatectomy specimens in 14 of 16 patients. The mean IGF-IR immunohistochemistry visual score was 2.1 (SD = 0.6) in biopsy and 1.1 (SD = 0.5) in prostatectomy specimens (P < 0.0001). Androgen receptor expression was also decreased and there was a trend for a decrease in downstream IGF-IR signaling components.Figitumumab is biologically active in prostate cancer. PSA declines in treatment-naive patients were observed, potentially mediated by IGF-IR effects on androgen receptor expression. These results support the clinical relevance of IGF-IR signaling in prostate cancer and justify further clinical trials.
Creativity, simulation, and conceptualization
Authors: Gilles Fauconnier
Journal: Behavioral and Brain Sciences (1999)

Understanding the role of simulation in conceptualization has become a priority for cognitive science. Barsalou makes a valuable contribution in that direction. The present commentary points to theoretical issues that need to be refined and elaborated in order to account for key aspects of meaning construction, such as negation, counterfactuals, quantification or analogy. Backstage cognition, with its elaborate bindings, blendings, and mappings, is more complex than Barsalou's discussion might suggest. Language does not directly carry meaning, but rather serves, along with countless other situational elements, as a powerful instrument for prompting its construction
Management of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians
Authors: Vincenza Snow
Journal: Annals of Internal Medicine (2007)

Venous thromboembolism is a common condition affecting 7.1 persons per 10,000 person-years among community residents. Incidence rates for venous thromboembolism are higher in men and African Americans and increase substantially with age. It is critical to treat deep venous thrombosis at an early stage to avoid development of further complications, such as pulmonary embolism or recurrent deep venous thrombosis. The target audience for this guideline is all clinicians caring for patients who have been given a diagnosis of deep venous thrombosis or pulmonary embolism. The target patient population is patients receiving a diagnosis of pulmonary embolism or lower-extremity deep venous thrombosis.
Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation
Authors: Claus-Werner Franzke, Cristina Cobzaru, Antigoni Triantafyllopoulou, Stefanie Löffek, Keisuke Horiuchi, David W. Threadgill, Thomas Kurz, Nico van Rooijen, Leena Bruckner-Tuderman, Carl P. Blobel
Journal: The Journal of Experimental Medicine (2012)

ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17(ΔKC)) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17(ΔKC) skin, and topical treatment of A17(ΔKC) mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (Egfr(ΔKC)) closely resembled A17(ΔKC) mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17-EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects.
Concentrations of specific dusts in swineries and the humoral response of swinery workers
Authors: T. Virtanen, P. Kalliokoski, P. Vilhunen, A. Taivainen, R. Mäntyjärvi
Journal: Allergy (1990)

The concentrations of swine epithelial antigen (SEA), swine urinary antigen (SUA) and swine feed antigen (SFA) were measured in swineries, SEA seems to be the most prevalent of the constituents measured. In the serum samples of the subjects studied, specific IgG antibodies against the antigens were frequently encountered. However, a difference was seen in the distribution of anti‐SUA‐IgG antibodies between swinery workers and a control group of students. The influence of the level of specific dust concentrations on specific antibody titers was studied statistically. Positive correlations were observed between stationary site SUA concentrations and anti‐SUA‐IgG and anti‐SEA‐IgG titers, respectively, pointing to an association between exposure and humoral response in swinery work. Consequently, our results suggest that the measurement of antibodies against SUA or its components could offer a basis for the estimation of the level of swinery work‐related respiratory exposure and for monitoring the quality of the working environment in swineries.
EVALUATION OF A BODY CHECKING POLICY CHANGE AS AN INJURY PREVENTION STRATEGY FOR NON-ELITE YOUTH ICE HOCKEY PLAYERS
Authors: CA Emery, A Black, A Macpherson, J Kang, B Hagel, M Romiti, W Meeuwisse
Journal: British Journal of Sports Medicine (2014)

Background In Pee Wee (ages 11–12) ice hockey, body checking is associated with an increased risk of injury and concussion. In 2011, research informed some provincial policy change, disallowing body checking in non-elite Pee Wee leagues. Objective To determine if the risk of injury and concussion differ for non-elite Pee Wee ice hockey players in leagues where body checking is permitted (Alberta, Canada) compared to leagues where prospective policy change disallows body checking (Ontario, Canada). Design Cohort study. Setting Ice hockey rinks (2011/12 season). Participants Non-elite (lower 70%) Pee Wee ice hockey players from Alberta (n=590) and Ontario (n=281). Risk factor assessment Exposure to a Pee Wee league where policy permits body checking. Other risk factors included previous concussion/injury, year of play, level of play, position and attitudes toward body checking. Main outcome Measurement Suspected concussions were identified by a team designate and referred to a sport medicine physician. Hockey injuries included those requiring medical attention or time loss. Results There were 101 game injuries (incidence rate [IR]=4.19/1000 game hours [95% CI; 3.38–5.18]), and 67 game concussions ([IR]=2.78/1000 game hours [95% CI; 2.19–3.52]) in Alberta and 14 game injuries (IR=1.60/1000 game hours [95% CI; 0.87–2.94]) and 8 concussions (IR=0.91/1000 game hours [95% CI; 0.41–2.06]) in Ontario. Based on multivariate poisson regression (adjusted for cluster, exposure hours and other risk factors), incidence rate ratio associated with policy allowing body checking was 2.97 (95% CI; 1.33–6.61) for game injury and 2.83 (95% CI; 1.09–7.31) for concussion. Conclusions The risk of injury and concussion was 3-fold greater in non-elite Pee Wee hockey players in leagues where body checking is permitted. This is similar to previous findings examining retrospective policy change. Policy change disallowing body checking is effective in preventing injury and concussion in non-elite youth ice hockey.
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Embryonic Antigens Shared Between Chemically Induced Lymphosarcomas and Fibrosarcomas of the Mouse&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S Ménard, M I Colnaghi
Journal: JNCI Journal of the National Cancer Institute (1975)

An antiserum obtained by the immunization of C57BL/HeDp mice with a pool of C3HF/Dp 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced fibrosarcomas exerted a specific cytotoxic activity in vitro on C57BL/HeDp chemically induced lymphosarcomas. Conversely, C57BL/HeDp spleen cells sensitized against C3Hf/Dp chemically induced lymphosarcomas or embryo cells were cytotoxic for plated cells of syngeneic DMBA-induced fibrosarcomas. Absorption studies with antiembryo and antilymphoma antisera showed that embryonic antigens were shared between lymphosarcomas and fibrosarcomas and that all serologically defined antigens present on lymphoma cells, including virus-related antigens, were also on fibrosarcoma cells.
Ras-Associated Protein-1 Regulates Extracellular Signal-Regulated Kinase Activation and Migration in Melanoma Cells: Two Processes Important to Melanoma Tumorigenesis and Metastasis
Authors: Ling Gao, Yunfeng Feng, Regina Bowers, Michelle Becker-Hapak, Jennifer Gardner, Laurin Council, Gerald Linette, Haibo Zhao, Lynn A. Cornelius
Journal: Cancer Research (2006)

Melanoma is one of the most devastating malignancies with a rising incidence and lack of effective treatments for advanced disease. Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway and altered expression of alpha(v)beta(3) integrin are critical for melanoma development and progression. Ras-associated protein-1 (Rap1), a Ras family member of the small GTPases, has emerged as a key mediator in these two important processes. In this study, we have shown Rap1 activation in cells derived from two human metastatic melanomas and also in three of seven cutaneous metastatic melanoma tissues. We found increased extracellular signal-regulated kinase (ERK) activity in the tumors with detected Rap1 activity that interestingly harbored neither BRAF nor N-Ras mutation, suggesting a role for Rap1 in ERK activation in vivo. We also showed Rap1 and ERK activation by both hepatocyte growth factor (HGF) and 8CPT-2Me-cAMP (an activator of Epac, a Rap1 guanine nucleotide exchange factor) in two human melanoma cell lines. In addition, the activation of ERK by HGF was reduced, at least in part, by small interfering RNAs against Rap1 and a dominant-negative Rap1. Finally, a functional role for Rap1 activation was shown by Rap1-induced alpha(v)beta(3) integrin activation and consequent increased melanoma cell migration in vitro. Taken together, these results show that Rap1 is involved in the activation of MAPK pathway and integrin activation in human melanoma and suggest a potential role for Rap1 in melanoma tumorigenesis and metastasis.
Defining low-dose corticosteroid: the pendulum still oscillates
Authors: Takashi Tagami, Hiroki Matsui, Hideo Yasunaga
Journal: European Respiratory Journal (2015)

We would like to thank P.R. Mohapatra and colleagues for their comments and interest in our study [1]. We also appreciate the editors of the European Respiratory Journal for giving us the opportunity to reply. The points made by P.R. Mohapatra and colleagues regard the following: 1) the corticotrophin test, 2) the dosage of corticosteroid, and 3) comorbidities as confounding factors for the use of corticosteroid. Low-dose corticosteroids for severe CAP: further studies are required to evaluate the optimal doses and types <http://ow.ly/OazFp>
Quality of Surveillance for Stage I Testis Cancer in the Community
Authors: Hua-yin Yu, Rodger A. Madison, Claude M. Setodji, Christopher S. Saigal
Journal: Journal of Clinical Oncology (2009)

Patients with clinical stage I testicular germ cell tumors have been managed with adjuvant radiotherapy, chemotherapy, or retroperitoneal lymph node dissection (RPLND). The use of surveillance-only strategies at referral centers has yielded survival outcomes comparable to those achieved with adjuvant therapy. We evaluated compliance with follow-up protocols developed at referral centers within the community.We identified patients with stage I testis cancer within a large private insurance claims database and calculated compliance of follow-up test use with guidelines from the National Comprehensive Cancer Network.Surveillance was widely used in the community. Compliance with surveillance and postadjuvant therapy follow-up testing was poor and degraded with increasing time from diagnosis. Nearly 30% of all surveillance patients received no abdominal imaging, chest imaging, or tumor marker tests within the first year of diagnosis. Patients who elected RPLND were most compliant with recommended follow-up testing within the first year. Recurrence rates were consistent with previously reported literature, despite poor compliance.Surveillance is a widely accepted strategy in clinical stage I testicular cancer treatment in the community. However, follow-up care recommendations developed at referral centers are not being adhered to in the community. Although recurrence rates are similar to those of reported literature, the clinical impact of noncompliance on recurrence severity and mortality are not known. Further prospective work needs to be done to evaluate this apparent quality of care problem in the community.
GENETIC CONTROL OF CELL-MEDIATED LYMPHOLYSIS IN MOUSE
Authors: Dolores J. Schendel, Fritz H. Bach
Journal: The Journal of Experimental Medicine (1974)

H-2 congenic mouse strains were tested in vitro to investigate the genetic control of cell-mediated lympholysis (CML). Combinations were selected such that differences in various segments of H-2 could be examined for their ability to stimulate production of effector cells and to serve as targets for lysis. Particular emphasis was directed towards understanding the roles of LD and SD. SD-region differences are important in the sensitization of effector cells and they also function as strong targets for lysis, or as markers for the CML targets. LD differences are also important for sensitization of cytotoxic effector cells, but they serve only as very weak targets for lysis. Collaboration occurs between LD and SD in generation of CML. The nature of this interaction can be of two types: together LD and SD can produce CML which neither difference alone can stimulate; LD can enhance a CML response stimulated by SD-region differences alone.
A cocoon immunisation strategy against pertussis for infants: does it make sense for Ontario?
Authors: G H Lim, S L Deeks, N S Crowcroft
Journal: Eurosurveillance (2014)

Pertussis deaths occur primarily among infants who have not been fully immunised. In Ontario, Canada, an adult booster dose was recently added to the publicly funded immunisation programme. We applied number-needed-to-treat analyses to estimate the number of adults that would need to be vaccinated (NNV) to prevent pertussis disease, hospitalisation and death among infants if a cocoon strategy were implemented. NNV=1/(P(M) X R) + 1/(P(F) X R), where P(M),P(F) (proportion of infants infected by mothers, fathers) were sourced from several studies. Rates of disease, hospitalisation or death (R) were derived from Ontario's reportable disease data and Discharge Abstract Database. After adjusting for under-reporting, the NNV to prevent one case, hospitalisation or death from pertussis was between 500-6,400, 12,000-63,000 and 1.1-12.8 million, respectively. Without adjustment, NNV increased to 5,000-60,000, 55,000-297,000 and 2.5-30.2 million, respectively. Rarer outcomes were associated with higher NNV. These analyses demonstrate the relative inefficiency of a cocoon strategy in Ontario, which has a well-established universal immunisation programme with relatively high coverage and low disease incidence. Other jurisdictions considering a cocoon programme should consider their local epidemiology.
Cytoprotective functions of amyloid precursor protein family members in stress signaling and aging
Authors: Arpita Kundu, Andreas Zymny, Steffi Chang, Nelli Röhner, Donat Kögel
Journal: Molecular Neurodegeneration (2013)

Poster presentation: Molecular Neurodegeneration: Basic biology and disease pathways Cannes, France. 10-12 September 2013.
Background: The amyloid precursor protein (APP) is processed via two different metabolic pathways: the amyloidogenic and the non-amyloidogenic pathway, the latter of which leading to generation of the secreted N-terminal APP fragment sAPPα [1]. Previous studies from our group suggest that sAPPα exerts potent neuroprotective effects and inhibits stress-triggered cell death via modulation of gene expression, as well as by antagonizing different types of neurotoxic stress [2]. It was also observed that the biochemical processing of APP is downregulated during aging which in turn reduced the secretion of sAPPα [3]. Based on these observations, we have studied the potential physiological function of sAPPα/APP and APLPs (APP like proteins) on the regulation of age-associated, stress induced signaling pathways, apoptosis and senescence.
Materials and methods: SH-SY5Y, PC12, IMR90 cells were used as cellular models. Depletion of APP, APLP1 (APP like protein 1) and APLP2 (APP like protein 2) in SH-SY5Y cells was achieved by stable lentiviral knockdown. To analyze the protective function of sAPPα, we have used conditioned supernatants of wild type APP overexpressing HEK cells and recombinant His-tagged sAPPα purified from yeast. The cells were treated with sAPPα prior to the addition of different stress stimuli (MG132, epoxomicin, UV, H2O2) after which cell death, gene expression and senescence were analyzed by MTT assays, caspase activity assays, Western blots and X-Gal staining respectively.
Results: Our data show that sAPPα can antagonize premature senescence induced by repetitive short term induction of proteasomal stress in IMR-90 cells and apoptosis triggered by prolonged proteasomal stress and other death stimuli in PC12, SH-SY5Y and IMR90 cells which was accompanied by a sAPPα-dependent inhibition of the JNK stress signaling pathway. In contrast, no significant changes in cell viability and apoptosis were observed when APP knockdown cells were pretreated with sAPPα.
Conclusions: Our observations suggest that sAPPα can antagonize both apoptosis and cellular senescence and requires expression of holo-APP to mediate its cytoprotective effects. They also support the notion that the physiological function of APP is linked to modulation of neuronal and brain aging.
Expression Pattern of Chemokine Receptor 6 (CCR6) and CCR7 in Squamous Cell Carcinoma of the Head and Neck Identifies a Novel Metastatic Phenotype
Authors: Jun Wang, Liqiang Xi, Jennifer L. Hunt, William Gooding, Theresa L. Whiteside, Zhuo Chen, Tony E. Godfrey, Robert L. Ferris
Journal: Cancer Research (2004)

Abstract Squamous cell carcinoma of the head and neck (SCCHN) metastasizes predictably to cervical lymph nodes, with low rates of distant metastases. Tumor cells can express various receptors that facilitate such metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCR), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. Chemokine receptor expression was evaluated in SCCHN, using paired primary and metastatic tumors cell lines, and paired primary and metastatic biopsies from the same patients. Quantitative reverse transcription-PCR showed a consistent pattern of CCR6 down-regulation and up-regulation of CCR7 in metastatic cells and tissues. Chemotaxis assays, ligand-induced receptor down-regulation, and specific antibody blocking experiments supported the quantitative reverse transcription-PCR results, indicating that these surface receptors were functional on metastatic tumor cells. Cells derived from a highly metastatic mouse model of SCCHN were used to confirm CCR7 up-regulation in tumor cells with higher metastatic potential. CCR6 down-regulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, whereas CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly up-regulated. Thus, CCR6, CCR7, and their ligands, normally important in controlling immune cell trafficking in response to inflammatory stimuli, may have an important role in determining the metastasis of SCCHN cells in vivo.
A reevaluation of cancer incidence near the Three Mile Island nuclear plant: the collision of evidence and assumptions.
Authors: S Wing, D Richardson, D Armstrong, D Crawford-Brown
Journal: Environmental Health Perspectives (1997)

Previous studies concluded that there was no evidence that the 1979 nuclear accident at Three Mile Island (TMI) affected cancer incidence in the surrounding area; however, there were logical and methodological problems in earlier reports that led us to reconsider data previously collected. A 10-mile area around TMI was divided into 69 study tracts, which were assigned radiation dose estimates based on radiation reading and models of atmospheric dispersion. Incident cancers from 1975 to 1985 were ascertained from hospital records and assigned to study tracts. Associations between accident doses and incidence rates of leukemia, lung cancer, and all cancer were assessed using relative dose estimates calculated by the earlier investigators. Adjustments were made for age, sex, socioeconomic characteristics, and preaccident variation in incidence. Considering a 2-year latency, the estimated percent increase per dose unit +/- standard error was 0.020 +/- 0.012 for all cancer, 0.082 +/- 0.032 for lung cancer, and 0.116 +/- 0.067 for leukemia. Adjustment for socioeconomic variables increased the estimates to 0.034 +/- 0.013, 0.103 +/- 0.035, and 0.139 +/- 0.073 for all cancer, lung cancer, and leukemia, respectively. Associations were generally larger considering a 5-year latency, but were based on smaller numbers of cases. Results support the hypothesis that radiation doses are related to increased cancer incidence around TMI. The analysis avoids medical detection bias, but suffers from inaccurate dose classification; therefore, results may underestimate the magnitude of the association between radiation and cancer incidence. These associations would not be expected, based on previous estimates of near-background levels of radiation exposure following the accident.