1,594 research outputs found
Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma
Background
Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism.
Case presentation
A 65-year-old patient with metastatic melanoma who progressed through two immunotherapy strategies with immune checkpoint inhibitor antibodies was enrolled in a phase I study (NCT02285101) and treated with 2 mg/kg intravenously, weekly pegylated recombinant arginase (BCT-100). The patient experienced no toxicities > grade 2 and entered a complete remission which is sustained for over 30 months. RNA-sequencing identified a number of transcriptomic pathway alterations compared to control samples. The tumour had absent expression of the recycling enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC) indicating a state of arginine auxotrophy, which was reconfirmed by immunohistochemistry, and validation in a larger cohort of melanoma tumour samples.
Conclusions
Targeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy
How citation boosts promote scientific paradigm shifts and Nobel Prizes
Nobel Prizes are commonly seen to be among the most prestigious achievements
of our times. Based on mining several million citations, we quantitatively
analyze the processes driving paradigm shifts in science. We find that
groundbreaking discoveries of Nobel Prize Laureates and other famous scientists
are not only acknowledged by many citations of their landmark papers.
Surprisingly, they also boost the citation rates of their previous
publications. Given that innovations must outcompete the rich-gets-richer
effect for scientific citations, it turns out that they can make their way only
through citation cascades. A quantitative analysis reveals how and why they
happen. Science appears to behave like a self-organized critical system, in
which citation cascades of all sizes occur, from continuous scientific progress
all the way up to scientific revolutions, which change the way we see our
world. Measuring the "boosting effect" of landmark papers, our analysis reveals
how new ideas and new players can make their way and finally triumph in a world
dominated by established paradigms. The underlying "boost factor" is also
useful to discover scientific breakthroughs and talents much earlier than
through classical citation analysis, which by now has become a widespread
method to measure scientific excellence, influencing scientific careers and the
distribution of research funds. Our findings reveal patterns of collective
social behavior, which are also interesting from an attention economics
perspective. Understanding the origin of scientific authority may therefore
ultimately help to explain, how social influence comes about and why the value
of goods depends so strongly on the attention they attract.Comment: 6 pages, 6 figure
Platy limestones. 10 case studies in the Classical Karst
Il progetto RoofOfRock, finanziato
nell’ambito del 2° bando di
cooperazione transfrontaliera
dell’Adriatico IPA 2007-2013 è iniziato
nell’ottobre 2012, si concluderà a fine
settembre del 2015 e coinvolge 10 partner
di 4 nazioni: Slovenia, Italia, Croazia e
Bosnia Erzegovina. In qualità di partner
associato e stakeholder partecipano le
regioni Friuli Venezia Giulia e Veneto.
Il progetto RoofOfRock ha tra le sue
finalità quelle di proporre un utilizzo
del calcare tabulare compatibile con
l’ambiente, di favorirne la protezione
e la promozione nonché di elaborare
delle linee guida utili per una sua
valorizzazione come patrimonio naturale
e culturale.Pri projektu RoofOfRock, ki je bil
izbran za sofinanciranje v okviru
2. poziva Jadranskega čezmejnega
programa IPA 2007–2013, sodeluje deset
projektnih partnerjev iz štirih držav, in
sicer iz Slovenije, Italije, s Hrvaške ter iz
Bosne in Hercegovine. Projekt se je začel
izvajati oktobra 2012 in se bo zaključil
konec septembra 2015. Pri projektu
sodelujeta tudi italijanski pokrajini
Furlanija - Julijska krajina kot deležnik in
Benečija kot pridruženi partner.
Namen projekta RoofOfRock je vzpostaviti
skupni temelj za trajnostno rabo, zaščito
in promocijo ploščastih apnencev
ter oblikovati uporabne smernice
za trajnostno upravljanje ploščastih
apnencev kot skupne naravne in kulturne
vrednote na celotnem projektnem
prostoru.The RoofOfRock Project is being
implemented under 2nd call
for ordinary projects of Adriatic
IPA CBC Programme 2007, joining 10
partners from 4 countries Slovenia, Italy,
Croatia and Bosnia and Herzegovina. It
started in October 2012 and is going to be
implemented until the end of September
2015. Two Italian Regions Friuli Venezia
Giulia and Veneto are participating as
stakeholder and associate partner .
The RoofOfRock intention is to establish
joint platform for platy limestone
sustainable use, preservation and
promotion, to create the relevant
guidelines and to upgrade both individual
and joint capacities in preserving such
common natural and cultural heritage
Hemiparasitism effect on Baccharis dracunculifolia DC. and consequences to its major galling herbivore
Epidemiologia da escoliose idiopática do adolescente em alunos da rede pública de Goiânia-GO
Optimization of Control Strategies for Non-Domiciliated Triatoma dimidiata, Chagas Disease Vector in the Yucatán Peninsula, Mexico
Chagas disease is the most important vector-borne disease in Latin America. Residual insecticide spraying has been used successfully for the elimination of domestic vectors in many regions. However, some vectors of non-domestic origin are able to invade houses, and they are now a key challenge for further disease control. We developed a mathematical model to predict the temporal variations in abundance of non-domiciliated vectors inside houses, based on triatomine demographic parameters. The reliability of the predictions was demonstrated by comparing these with different sets of insect collection data from the Yucatan peninsula, Mexico. We then simulated vector control strategies based on insecticide spraying, insect, screens and bednets to evaluate their efficacy at reducing triatomine abundance in the houses. An optimum reduction in bug abundance by at least 80% could be obtained by insecticide application only when doses of at least 50 mg/m2 were applied every year within a two-month period matching the house invasion season by bugs. Alternatively, the use of insect screens consistently reduced bug abundance in the houses and offers a sustainable alternative. Such screens may be part of novel interventions for the integrated control of various vector-borne diseases
Comparison of the CBA-H and SF-36 for the screening of the psychological and behavioural variables in chronic dialysis patients
The aim of the study was to perform an analysis of the emotional reactions, perception of stressful life and behavioural changes related to Haemodialysis (HD) in order to identify those variables that can improve lifestyle and the adherence to treatment. Some psycho- metric assessment, such as the Cognitive Behavioural Assessment, Hospital Form, (CBA- H) and the Health Survey (SF-36), which provides two indexes: the Physical Component Score (PCS) and the Mental Component Score (MCS), are suitable to assess a patient’s psychological and behavioural style and their health-related quality of life. The study involved 37 Italian out-patients with end-stage renal disease under HD therapy. We calcu- lated the Spearman correlation between variables of CBA-H, SF-36, age and time on HD. We also performed a multivariate linear regression using the CBA-H variables as predictors and PCS and MCS as dependent variables. From the CBA-H, 95% of participants self- reported psychological characteristics comparable to Type A personality, which identifies an anxious, hyperactive and hostile subject. Physical limitations were found to be directly pro- portional to the time on dialysis (rs = -0.42). The condition of perceived stress worsens the state of mental health (rs = -0.68) and general health perception (rs = -0.44). The condition of vital exhaustion correlates both the PCS and the MCS (p<0.01) with possible outcomes of physical and mental illness. The psychological wellbeing of a dialyzed patient could be due to the combination of several factors, including life parameters, the positive perception of psychosocial outcomes, and the perceived quality of life. A multidisciplinary team (neurolo- gists, psychiatrists, psychologists, and nurses) is essential to plan effective psychological and psychotherapeutic interventions to improve a mind-body integration
Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC
We present the first results of meson production in the K^+K^- decay channel
from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by
the PHENIX detector at RHIC. Precision resonance centroid and width values are
extracted as a function of collision centrality. No significant variation from
the PDG accepted values is observed. The transverse mass spectra are fitted
with a linear exponential function for which the derived inverse slope
parameter is seen to be constant as a function of centrality. These data are
also fitted by a hydrodynamic model with the result that the freeze-out
temperature and the expansion velocity values are consistent with the values
previously derived from fitting single hadron inclusive data. As a function of
transverse momentum the collisions scaled peripheral.to.central yield ratio RCP
for the is comparable to that of pions rather than that of protons. This result
lends support to theoretical models which distinguish between baryons and
mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be
submitted to Physical Review C as a regular article. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance
This paper presents DELPHI measurements and interpretations of
cross-sections, forward-backward asymmetries, and angular distributions, for
the e+e- -> ffbar process for centre-of-mass energies above the Z resonance,
from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are
consistent with the predictions of the Standard Model and are used to study a
variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering
and several models which include physics beyond the Standard Model: the
exchange of Z' bosons, contact interactions between fermions, the exchange of
gravitons in large extra dimensions and the exchange of sneutrino in R-parity
violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.
A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events
Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the
Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy
and momentum constraint methods. The results are expressed as deviations from
the nominal LEP centre-of-mass energy, measured using other techniques. The
results are found to be compatible with the LEP Energy Working Group estimates
for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.
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