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Laurien J. Zeverijn Eleonora J. Looze Subotheni Thavaneswaran J. Maxime van Berge Henegouwen Robert J. Simes Louisa R. Hoes Katrin M. Sjoquist Hanneke van der Wijngaart Lucille Sebastian Birgit S. Geurts Chee K. Lee Gijsbrecht F. de Wit David Espinoza Paul Roepman Frank P. Lin Anne M. L. Jansen Wendy W. J. de Leng Vincent van der Noort Lindsay V. M. Leek Filip Y. F. L. de Vos Carla M. L. van Herpen Hans Gelderblom Henk M. W. Verheul David M. Thomas Emile E. Voest 《International journal of cancer. Journal international du cancer》2023,153(7):1413-1422
The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible. 相似文献
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The global plastic production is reaching new altitudes every year. Growing production of petroleum-based plastics has incurred in disposal issues raising the concerns of plastic pollution and impact to the environment. These issues have encouraged innovation and research activities in the field of bioplastics, offering alternatives for conventional plastics. In recent years, global bioplastic production has also witnessed tremendous growth and expansion. Some of the main drivers of this growth are innovative biopolymers such as Polylactic acid (PLA) and Polyhydroxyalkanoates (PHAs). However, industrial expenses to produce bioplastics are much higher when compared to petroleum-derived plastics (e.g. industrial PHA production is estimated to be 5–10 times more expensive than petroleum-derived polymers). In this regard, globally many researchers have investigated for more environmentally friendly and cost-effective alternatives to produce plastics. One potential option to pursue would be to explore agri-food wastes and by-products for bioplastic production. This would not only reduce the volume of wastes and by-products, but also production costs incurred. This review paper provides an overview of bioplastics, including production methods and possibilities of industrial food waste valorization for bioplastic production. 相似文献
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Elizabeth A. Mosley PhD MPH Amy J. Schulz PhD MPH MSW Lisa H. Harris MD PhD Barbara A. Anderson PhD 《Women & health》2020,60(7):806-820
ABSTRACT Abortion is legal in South Africa, but negative abortion attitudes remain common and are poorly understood. We used nationally representative South African Social Attitudes Survey data to analyze abortion attitudes in the case of fetal anomaly and in the case of poverty from 2007 to 2016 (n = 20,711; ages = 16+). We measured correlations between abortion attitudes and these important predictors: religiosity, attitudes about premarital sex, attitudes about preferential hiring and promotion of women, and attitudes toward family gender roles. Abortion acceptability for poverty increased over time (b = 0.05, p < .001), but not for fetal anomaly (b = ?0.008, p = .284). Highly religious South Africans reported lower abortion acceptability in both cases (Odds Ratio (OR)anomaly = 0.85, p = .015; ORpoverty = 0.84, p = .02). Premarital sex acceptability strongly and positively predicted abortion acceptability (ORanomaly = 2.63, p < .001; ORpoverty = 2.46, p < .001). Attitudes about preferential hiring and promotion of women were not associated with abortion attitudes, but favorable attitudes about working mothers were positively associated with abortion acceptability for fetal anomaly ((ORanomaly = 1.09, p = .01; ORpoverty = 1.02, p = .641)). Results suggest negative abortion attitudes remain common in South Africa and are closely tied to religiosity, traditional ideologies about sexuality, and gender role expectations about motherhood. 相似文献
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Raquel Blazquez Eva Rietkötter Britta Wenske Darius Wlochowitz Daniela Sparrer Elena Vollmer Gunnar Müller Julia Seegerer Xueni Sun Katja Dettmer Alonso Barrantes-Freer Lena Stange Kirsten Utpatel Annalen Bleckmann Hannes Treiber Hanibal Bohnenberger Christof Lenz Matthias Schulz Christian Reimelt Christina Hackl Marian Grade Deram Büyüktas Laila Siam Marko Balkenhol Christine Stadelmann Dieter Kube Michael P. Krahn Martin A. Proescholdt Markus J. Riemenschneider Matthias Evert Peter J. Oefner Chistoph A. Klein Uwe K. Hanisch Claudia Binder Tobias Pukrop 《International journal of cancer. Journal international du cancer》2020,146(11):3170-3183
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