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Andrew X. Zhu Richard S. Finn Yoon-Koo Kang Chia-Jui Yen Peter R. Galle Josep M. Llovet Eric Assenat Giovanni Brandi Kenta Motomura Izumi Ohno Bruno Daniele Arndt Vogel Tatsuya Yamashita Chih-Hung Hsu Guido Gerken John Bilbruck Yanzhi Hsu Kun Liang Ryan C. Widau Chunxiao Wang Paolo Abada Masatoshi Kudo 《British journal of cancer》2021,124(8):1388
Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH () and REACH-2 ( NCT01140347).Subject terms: NCT02435433Oncology, Biomarkers 相似文献
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Elia Ciani Romain Fontaine Gersende Maugars Naama Mizrahi Ian Mayer Berta Levavi‐Sivan Finn‐Arne Weltzien 《Journal of pineal research》2019,67(3)
The hormone melatonin connects environmental cues, such as photoperiod and temperature, with a number of physiological and behavioural processes, including seasonal reproduction, through binding to their cognate receptors. This study reports the structural, functional and physiological characterization of five high‐affinity melatonin receptors (Mtnr1aaα, Mtnr1aaβ, Mtnr1ab, Mtnr1al, Mtnr1b) in Atlantic salmon. Phylogenetic analysis clustered salmon melatonin receptors into three monophyletic groups, Mtnr1A, Mtnr1Al and Mtnr1B, but no functional representative of the Mtnr1C group. Contrary to previous studies in vertebrates, pharmacological characterization of four receptors in COS‐7, CHO and SH‐SY5Y cell lines (Mtnr1Aaα, Mtnr1Aaβ, Mtnr1Ab, Mtnr1B) showed induction of intracellular cAMP levels following 2‐iodomelatonin or melatonin exposure. No consistent response was measured after N‐acetyl‐serotonin or serotonin exposure. Melatonin receptor genes were expressed at all levels of the hypothalamo‐pituitary‐gonad axis, with three genes (mtnr1aaβ, mtnr1ab and mtnr1b) detected in the pituitary. Pituitary receptors displayed daily fluctuations in mRNA levels during spring, prior to the onset of gonadal maturation, but not in autumn, strongly implying a direct involvement of melatonin in seasonal processes regulated by the pituitary. To the best of our knowledge, this is the first report of cAMP induction mediated via melatonin receptors in a teleost species. 相似文献
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Meng-Lay Lin Hetal Patel Judit Remenyi Christopher R.S. Banerji Chun-Fui Lai Manikandan Periyasamy Ylenia Lombardo Claudia Busonero Silvia Ottaviani Alun Passey Philip R. Quinlan Colin A. Purdie Lee B. Jordan Alastair M. Thompson Richard S. Finn Oscar M. Rueda Carlos Caldas Jesus Gil R. Charles Coombes Frances V. Fuller-Pace Andrew E. Teschendorff Laki Buluwela Simak Ali 《Oncotarget》2015,6(25):21685-21703
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Long‐term consequences of pain,anxiety and agitation for critically ill older patients after an intensive care unit stay 下载免费PDF全文
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