The Vehicle, Fall 2008

Table of Contents DwIFoFErREINdTPhilip Gallagherpage 17 LeftoversAmanda Vealepage 18 the bogGrace Lawrencepage 19 Visitor\u27s Morning on EarthSteven T. Coxpage 20 The Moon Man Philip Gallagherpage 21 SearchingsAmanda Vealepage 23 Becoming WiseAmanda Vealepage 24 PerennialsAmanda Vealepage 26 SoldierMary Lieskepage 27 Desecration of a RelicAmanda Vealepage 29 New LifeJennifer O\u27Neilpage 30 GardenerKrystina Levyapage 43 The Reasons WhyMary Lieskepage 44 Dining at the MortuaryAmanda Vealepage 45 Poetry Hop Scotch BehopJake Dawsonpage 1 Empty RoomAmanda Vealepage 2 Mantis (from memory) Muddy ShoesGina Marie LoBiancopage 3 MEMOSamuel Clowardpage 5 MathMary Lieskepage 7 To a Little Black GirlJustin Sudkamppage 8 Government OfficeSamuel Clowardpage 9 FirstKellen Fasnachtpage 10 Seeing Artichoke, Call MeAmanda Vealepage 11 TrumpetSarah Fairchildpage 12 That\u27s the StuffJake Dawsonpage 13 Your Hair is ThinningAmanda Vealepage 15 UnableDonica Millerpage 16 Dance PartnersSamantha Sauerpage 32 I StillMegan Mathypage 33 IncandescenceSarah Fairchildpage 34 Stone CraneBrendan Hughespage 35 The Road TakenSamantha Sauerpage 36 YouMegan Mathypage 37 Zhangjiajie National Forest Park, Zhangjiajie, ChinaBrendan Hughespage 38 Spotlight on 2008 Chapbook LessonsGlen Davispage 62 Interview with Glen DavisRebecca Griffithpage 64 Contributorspage 69 Submission Guidelines/Reading Event Blues Mad FoolJake Dawsonpage 47 Good WomanJake Dawsonpage 49 Good ManJake Dawsonpage 51 And I Miss YouDonica Millerpage 53 Entropy of Your ShirtAmanda Vealepage 56 Mavericks Philip Gallagherpage 57 Untitled [It\u27s 10:15 p.m....]Philip Gallagherpage 59 Prose A Birdhouse for GrandpaLeslie Hancockpage 39 MotivationMary Lieskepage 55 Art Forgotten GardenBrendan Hughescovers BeMegan Mathypage 31https://thekeep.eiu.edu/vehicle/1088/thumbnail.jp

Nociceptin/orphanin FQ (N/OFQ) modulates immunopathology and airway hyperresponsiveness representing a novel target for the treatment of asthma.

BACKGROUND AND PURPOSE: There is evidence supporting a role for the nociceptin/orphanin FQ (N/OFQ; NOP) receptor and its endogenous ligand N/OFQ in the modulation of neurogenic inflammation, airway tone and calibre. We hypothesized that NOP receptor activation has beneficial effects upon asthma immunopathology and airway hyperresponsiveness. Therefore, the expression and function of N/OFQ and the NOP receptor were examined in healthy and asthmatic human airway tissues. The concept was further addressed in an animal model of allergic asthma. EXPERIMENTAL APPROACH: NOP receptor expression was investigated by quantitative real-time PCR. Sputum N/OFQ was determined by RIA. N/OFQ function was tested using several assays including proliferation, migration, collagen gel contraction and wound healing. The effects of N/OFQ administration in vivo were studied in ovalbumin (OVA)-sensitized and challenged mice. KEY RESULTS: NOP receptors were expressed on a wide range of human and mouse immune and airway cells. Eosinophils expressed N/OFQ-precursor mRNA and their number correlated with N/OFQ concentration. N/OFQ was found in human sputum and increased in asthma. Additionally, in asthmatic human lungs N/OFQ immunoreactivity was elevated. NOP receptor activation inhibited migration of immunocytes and increased wound healing in airway structural cells. Furthermore, N/OFQ relaxed spasmogen-stimulated gel contraction. Remarkably, these findings were mirrored in OVA-mice where N/OFQ treatment before or during sensitization substantially reduced airway constriction and immunocyte trafficking to the lung, in particular eosinophils. N/OFQ also reduced inflammatory mediators and mucin production. CONCLUSIONS AND IMPLICATIONS: We demonstrated a novel dual airway immunomodulator/bronchodilator role for N/OFQ and suggest targeting this system as an innovative treatment for asthma

The Vehicle, Fall 2008

Table of Contents DwIFoFErREINdTPhilip Gallagherpage 17 LeftoversAmanda Vealepage 18 the bogGrace Lawrencepage 19 Visitor\u27s Morning on EarthSteven T. Coxpage 20 The Moon Man Philip Gallagherpage 21 SearchingsAmanda Vealepage 23 Becoming WiseAmanda Vealepage 24 PerennialsAmanda Vealepage 26 SoldierMary Lieskepage 27 Desecration of a RelicAmanda Vealepage 29 New LifeJennifer O\u27Neilpage 30 GardenerKrystina Levyapage 43 The Reasons WhyMary Lieskepage 44 Dining at the MortuaryAmanda Vealepage 45 Poetry Hop Scotch BehopJake Dawsonpage 1 Empty RoomAmanda Vealepage 2 Mantis (from memory) Muddy ShoesGina Marie LoBiancopage 3 MEMOSamuel Clowardpage 5 MathMary Lieskepage 7 To a Little Black GirlJustin Sudkamppage 8 Government OfficeSamuel Clowardpage 9 FirstKellen Fasnachtpage 10 Seeing Artichoke, Call MeAmanda Vealepage 11 TrumpetSarah Fairchildpage 12 That\u27s the StuffJake Dawsonpage 13 Your Hair is ThinningAmanda Vealepage 15 UnableDonica Millerpage 16 Dance PartnersSamantha Sauerpage 32 I StillMegan Mathypage 33 IncandescenceSarah Fairchildpage 34 Stone CraneBrendan Hughespage 35 The Road TakenSamantha Sauerpage 36 YouMegan Mathypage 37 Zhangjiajie National Forest Park, Zhangjiajie, ChinaBrendan Hughespage 38 Spotlight on 2008 Chapbook LessonsGlen Davispage 62 Interview with Glen DavisRebecca Griffithpage 64 Contributorspage 69 Submission Guidelines/Reading Event Blues Mad FoolJake Dawsonpage 47 Good WomanJake Dawsonpage 49 Good ManJake Dawsonpage 51 And I Miss YouDonica Millerpage 53 Entropy of Your ShirtAmanda Vealepage 56 Mavericks Philip Gallagherpage 57 Untitled [It\u27s 10:15 p.m....]Philip Gallagherpage 59 Prose A Birdhouse for GrandpaLeslie Hancockpage 39 MotivationMary Lieskepage 55 Art Forgotten GardenBrendan Hughescovers BeMegan Mathypage 31https://thekeep.eiu.edu/vehicle/1088/thumbnail.jp

An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma: final analysis and a validated prognostic scoring system

Background: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. Patients and methods: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). Results: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. Conclusions: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work. © 2018 Elsevier Lt

An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma:Final analysis and a validated prognostic scoring system

BACKGROUND: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. PATIENTS AND METHODS: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). RESULTS: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. CONCLUSIONS: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work