68 research outputs found
Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma
- Author
- A Grieco
- A Sandler
- A-L Cheng
- AB Siegel
- AL Cheng
- AX Zhu
- AX Zhu
- BT Hennessy
- C Hsu
- C Hsu
- C Twelves
- C-H Hsu
- DH Palmer
- F Farinati
- H C Toh
- H Hurwitz
- HB El-Serag
- J Sakamoto
- JM Llovet
- JM Llovet
- KD Miller
- L-T Hsiao
- LG Ensign
- LT Chen
- MB Thomas
- P-J Chen
- R Capocaccia
- R J Epstein
- R Pang
- R Yamaguchi
- S Collette
- S Wilhelm
- SL Chan
- SM Wilhelm
- SR Vora
- T-S Yang
- T-Y Chao
- YZ Patt
- Z-Z Lin
- Publication venue
- Nature Publishing Group
- Publication date
- 15/06/2011
- Field of study
Molecularly targeted agents with anti-angiogenic activity, including bevacizumab, have demonstrated clinical activity in patients with advanced /metastatic hepatocellular carcinoma (HCC). This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population. METHODS: Histologically proven/clinically diagnosed advanced HCC patients received bevacizumab 7.5 mg kg(-1) on day 1 and capecitabine 800 mg m(-2) twice daily on days 1-14 every 3 weeks as first-line therapy. RESULTS: A total of 45 patients were enrolled; 44 (96%) had extrahepatic metastasis and/or major vessel invasion and 30( 67%) had hepatitis B. No grade 3/4 haematological toxicity occurred. Treatment-related grade 3/4 non-haematological toxicities included diarrhoea (n = 2, 4%), nausea/ vomiting ( n = 1, 2%), gastrointestinal bleeding (n = 4, 9%) and hand- foot syndrome (n = 4, 9%). The overall response rate ( RECIST) was 9% and the disease control rate was 52%. Overall , median progression-free survival (PFS) and overall survival(OS) were 2.7 and 5.9 months, respectively. Median PFS and OS were 3.6 and 8.2 months, respectively, for Cancer of the Liver Italian Programme (CLIP) score <= 3 patients, and 1.4 and 3.3 months, respectively, for CLIP score 4 patients. CONCLUSION: The bevacizumab-capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC
Expression of human Piwi-likegenes is associated with prognosis for soft tissue sarcoma patients
- Author
- A Aravin
- A Girard
- A Krieg
- AI Kalmykova
- AK Sharma
- AR Morris
- Christine LautenschlÀger
- D Qiao
- DN Cox
- Franziska Koser
- G He
- G Sun
- H Taubert
- H Taubert
- Hans-JĂŒrgen Holzhausen
- HB Megosh
- Helge Taubert
- HH Vora
- J Brennecke
- JH Lee
- JJ Liu
- L Anderson
- L Cerutti
- L Li
- LF Grochola
- MA Carmell
- Matthias Bache
- Matthias Kappler
- NC Lau
- P WĂŒrl
- Peter WĂŒrl
- PK Chaudhuri
- Q Wu
- QE Wang
- S PeirĂł
- Steffen Göbel
- Sven Wach
- T Sasaki
- Thomas Greither
- VV Vagin
- W He
- X Liu
- Y Ye
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Targeted therapies for ER+/HER2- metastatic breast cancer
- Author
- A Ali
- A Boulay
- AC Wolff
- AU Buzdar
- C Curtis
- C Gewinner
- C Yu
- CA Lange
- Cancer Genome Atlas N
- CK Osborne
- D Hanahan
- D Juric
- D Sarker
- DA Yardley
- DA Yardley
- DR Robinson
- E Hirsch
- EA Musgrove
- F Andre
- F Andre
- F Andre
- F Andre
- F Andre
- F Cardoso
- Fabrice André
- G Perez-Tenorio
- GI Shapiro
- H Iwase
- H Zhang
- HB Muss
- I Migliaccio
- IA Mayer
- IAM Treilleux
- IG Campbell
- J Baselga
- J Baselga
- J Rodon
- J Tabernero
- JE Abraham
- JE Bolden
- K Stemke-Hale
- L Binkhorst
- L Wang
- LA DeGraffenried
- M Dokmanovic
- M Piccart
- M Yu
- MJ Ellis
- MJ Ellis
- Monica Arnedos
- Mutsuko Yamamoto-Ibusuki
- N Sengupta
- N Turner
- OJ Shah
- P Marks
- PJ Roberts
- PJ Stephens
- PN Munster
- R Ferraldeschi
- R Jeselsohn
- R Margueron
- RL Piekarz
- RL Theriault
- RS Finn
- RS Finn
- S Chan
- S Gupta
- SM Maira
- SR Vora
- T Bachelot
- T Simoncini
- TW Miller
- W Fischle
- W Toy
- X Fu
- Y Jin
- Y Samuels
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
- Author
- A Abbate
- A Abhyankar
- A Adams
- A Agafina
- A Akyea-Djamson
- A Alan
- A Alfieri
- A Alfrey
- A Alvarisqueta
- A Amos
- A Anadiotis
- A Anneveldt
- A Antolick
- A Arthur
- A Aslam
- Abaci F
- Abdullakutty J
- Abhaichand R
- Abib E Jr
- Aboufakher R
- Abrantes J
- Abreu M
- Abulencia K
- Acampora D
- Acampora M
- Accini Mendoza Jl
- Aceto L
- Acevedo B
- Acevedo L
- Acheatel R
- Actis Mv
- Adams M
- Adjic Nc
- Affaki Gs
- Agarwal Dk
- Aggarwal Rk
- Agosta Gf
- Aguilar M
- Aguilar M
- Ahire N
- Ahmad I
- Ahmed Sh
- Ahn Y
- Aish B
- Aiub F
- Aiub J
- Ajax K
- Ajioka M
- Akai Y
- Akatova E
- Akrap B
- Al Joundi T
- Al-Khalili F
- Albisu J
- Alcalde Jm
- Alcide P
- Alfonso T
- Allen J
- Alllison Dc
- Almaliky T
- Amerena J
- Andersen K
- Andor M
- Angelova I
- Angiolillo D
- Anita S
- Anker Sd
- Antalik L
- Antonicelli R
- Aparicio Cv
- Apel T
- Apostolovic S
- Ara M
- Aragorn L
- Arango Jl
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- Ardissino D
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- Argiolas G
- Arif I
- Armas E
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- Asim Oktay Ao
- Assarsson E
- Ata B
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- Atieh M
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- Avalos V
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- Zineldine A.
- Zirlik A
- Zucchetti C
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1ÎČ, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1ÎČ innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial
- Author
- Abbas J
- Abbate A
- Abdullakutty J
- Abhyanakar AD
- Aboyans V
- Abrantes JAM
- Abu-Fadel M
- Acevedo M
- Adamkova V
- Adhyapak S
- Agarwal H
- Aggarwal R
- Aggarwal RK
- Aguirre A
- Ahmed H
- Ahremark U
- Ahuad Guerrero RA
- Aidar Ayoub JC
- Airaksinen JK
- Aitken D
- Akatova E
- Akhter F
- Ako J
- Akright L
- Akyea-Djamson A
- Al Joundi T
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- Willems FF
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- Wollaert B
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- Wongpraparut N
- Worner Diz F
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- Xatzitolios A
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- Xu B
- Xu D
- Xu X
- Yagensky A
- Yakushin S
- Yan AT-K
- Yan BPY
- Yanez M
- Yang E
- Yang X
- Yang X
- Yao Z
- Yazdani S
- Yerra SK
- Yin W-H
- Yong H
- Yoon JH
- Younis L
- Yu Y
- Yuan Z
- Yusoff K
- Zahger D
- Zaidman CJ
- Zainea M
- Zaman A
- Zeiher AM
- Zhang W
- Zhang X
- Zhang Z
- Zhao X
- Zheng Y
- Zheng Z
- Zhou Y
- Zhu H
- Zirlik A
- Zizka J
- Zong W
- Zrazhevsky K
- Zuniga JDH
- Zurakowski A
- Zuran I
- Zweiker R
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2019
- Field of study
Aimsâ The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisinâkexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18Â 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (â„1.8âmmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and resultsâ Median follow-up was 2.8âyears. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (nâ=â2) or Type 5 (nâ=â5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77â0.95; Pâ=â0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77â0.99; Pâ=â0.032) and Type 2 (0.77, 0.61â0.97; Pâ=â0.025), but not Type 4 MI. Conclusionâ After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
- Author
- A Abbott
- A Abou-Raya
- A Aljandali
- A Ambesi-Impiombato
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- A Besarab
- A Brzezinski
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- The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group
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- Publication venue
- Publication date
- 09/08/2008
- Field of study
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial
- Author
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- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 04/01/2019
- Field of study
Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for â„3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C â„100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for â„3 years, if baseline LDL-C is â„100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402
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- Author
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- Aarup Petersen H
- Abbaneo D
- Abbiendi G
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- Abdullah Al-Mashad M
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- Publication venue
- Springer Nature on behalf of SISSA
- Publication date
- 30/01/2024
- Field of study
A preprint version of the article is available at arXiv:2308.01253v2 [hep-ex], https://arxiv.org/abs/2308.01253v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-22-009 (CMS Public Pages). Report number: CMS-HIG-22-009, CERN-EP-2023-110.A measurement of the Higgs boson (H) production via vector boson fusion (VBF) and its decay into a bottom quark-antiquark pair (bbÂŻ) is presented using proton-proton collision data recorded by the CMS experiment at sâ = 13 TeV and corresponding to an integrated luminosity of 90.8 fbâ1. Treating the gluon-gluon fusion process as a background and constraining its rate to the value expected in the standard model (SM) within uncertainties, the signal strength of the VBF process, defined as the ratio of the observed signal rate to that predicted by the SM, is measured to be ÎŒqqHHbbÂŻ = 1.01 +0.55â0.46. The VBF signal is observed with a significance of 2.4 standard deviations relative to the background prediction, while the expected significance is 2.7 standard deviations. Considering inclusive Higgs boson production and decay into bottom quarks, the signal strength is measured to be ÎŒincl.HbbÂŻ = 0.99 +0.48â0.41, corresponding to an observed (expected) significance of 2.6 (2.9) standard deviations.SCOAP3, STFC; Marie-Curie program and the European Research Council and Horizon 2020 Gran
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Search for new Higgs bosons via same-sign top quark pair production in association with a jet in proton-proton collisions at âs = 13 TeV
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- Aarup Petersen H
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- Yusuff I
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- Zuolo D
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- Publication venue
- Elsevier
- Publication date
- 02/02/2024
- Field of study
Data availability:
Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in âCMS data preservation, re-use and open access policyâ available online at: https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2 .A preprint of this article is available online at arXiv:2311.03261v2 [hep-ex] https://arxiv.org/abs/2311.03261v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-010 (CMS Public Pages)A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp â tH/A â ttÂŻc and pp â tH/A â ttÂŻu processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fbâ1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200-1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM.SCOAP3
Recommended from our members
Search for long-lived heavy neutral leptons with lepton flavour conserving or violating decays to a jet and a charged lepton
- Author
- Aarrestad TK
- Aarup Petersen H
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- Publication venue
- Springer Nature on behalf of SISSA
- Publication date
- 19/03/2024
- Field of study
A preprint version of the article is available at arXiv:2312.07484v3 [hep-ex], https://arxiv.org/abs/2312.07484 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-013 (CMS Public Pages)A search for long-lived heavy neutral leptons (HNLs) is presented, which considers the hadronic final state and coupling scenarios involving all three lepton generations in the 2-20 GeV HNL mass range for the first time. Events comprising two leptons (electrons or muons) and jets are analyzed in a data sample of proton-proton collisions, recorded with the CMS experiment at the CERN LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fbâ1. A novel jet tagger, based on a deep neural network, has been developed to identify jets from an HNL decay using various features of the jet and its constituent particles. The network output can be used as a powerful discriminating tool to probe a broad range of HNL lifetimes and masses. Contributions from background processes are determined from data. No excess of events in data over the expected background is observed. Upper limits on the HNL production cross section are derived as functions of the HNL mass and the three coupling strengths VâN to each lepton generation â and presented as exclusion limits in the coupling-mass plane, as lower limits on the HNL lifetime, and on the HNL mass. In this search, the most stringent limit on the coupling strength is obtained for pure muon coupling scenarios; values of |VÎŒN|2 > 5 (4) Ă 10â7 are excluded for Dirac (Majorana) HNLs with a mass of 10 GeV at a confidence level of 95% that correspond to proper decay lengths of 17 (10) mm.SCOAP3
- âŠ