Browsing by Author "Anscher, Mitchell S."

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    Ensuring sample quality for blood biomarker studies in clinical trials: a multicenter international study for plasma and serum sample preparation
    (2017-12) Kong, Feng-Ming (Spring); Zhao, Lujun; Wang, Luhua; Chen, Yuhchyau; Hu, Jie; Fu, Xiaolong; Bai, Chunxue; Wang, Li; Lawrence, Theodore S.; Anscher, Mitchell S.; Dicker, Adam; Okunieff, Paul; Radiation Oncology, School of Medicine
    Background Sample quality is critical for biomarker detection in oncology, and platelet degradation and contamination in plasma have a remarkable impact on the ability to accurately quantify many blood-based biomarkers. Platelet factor 4 (PF4) can be used as an indicator to monitor sample quality. This multicenter study aimed to determine the impact of critical components of the blood sample handling process on platelet degradation/contamination and to establish an optimal method for collecting platelet-poor plasma samples. Methods At each of six participating centers, blood samples were drawn from 12–13 healthy volunteers. Serum and plasma samples were prepared from whole blood samples using nine different methods that have been commonly used in ongoing multicenter trials. PF4 levels in the prepared samples were measured by enzyme-linked immunosorbent assay (ELISA). Paired t-tests were used for statistical analysis. Results Blood samples were collected from 74 subjects enrolled in six centers. PF4 levels were significantly higher in serum samples than in plasma samples (P<0.001), in plasma samples from blood that sat at room temperature for 5 minutes (P=0.021), in plasma samples prepared at an insufficient centrifugal force (P<0.001), and in plasma samples prepared from blood that sat for longer than 4 hours on ice (P=0.001). For each method, the PF4 levels did not differ significantly among the centers or between Chinese and American subjects. The methods that resulted in normal levels of PF4 involved keeping blood samples on ice for 30 minutes to <4 hours and centrifugation at 2,500–3,000 ×g for 30 min. Conclusions This multicenter study evaluated multiple blood sample handling conditions for minimizing platelet degradation during plasma serum preparation and determined an optimal method for preparing platelet-poor plasma. The findings of this study can be applied in future blood biomarker studies.
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    Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy
    (Oxford, 2021-10) Prasanna, Pataje G.; Citrin, Deborah E.; Hildesheim, Jeffrey; Ahmed, Mansoor M.; Venkatachalam, Sundar; Riscuta, Gabriela; Xi, Dan; Zheng, Guangrong; van Deursen, Jan; Goronzy, Jorg; Kron, Stephen J.; Anscher, Mitchell S.; Sharpless, Norman E.; Campisi, Judith; Brown, Stephen L.; Niedernhofer, Laura J.; O’Loghlen, Ana; Georgakilas, Alexandros G.; Paris, Francois; Gius, David; Gewirtz, David A.; Schmitt, Clemens A.; Abazeed, Mohamed E.; Kirkland, James L.; Richmond, Ann; Romesser, Paul B.; Lowe, Scott W.; Gil, Jesus; Mendonca, Marc S.; Burma, Sandeep; Zhou, Daohong; Coleman, C. Norman; Radiation Oncology, School of Medicine
    Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction of tumor cell senescence is also one of the underlying mechanisms by which cancer therapies exert antitumor activity. However, an increasing body of evidence from preclinical studies demonstrates that radiation and chemotherapy cause accumulation of senescent cells (SnCs) both in tumor and normal tissue. SnCs in tumors can, paradoxically, promote tumor relapse, metastasis, and resistance to therapy, in part, through expression of the senescence-associated secretory phenotype. In addition, SnCs in normal tissue can contribute to certain radiation- and chemotherapy-induced side effects. Because of its multiple roles, cellular senescence could serve as an important target in the fight against cancer. This commentary provides a summary of the discussion at the National Cancer Institute Workshop on Radiation, Senescence, and Cancer (August 10-11, 2020, National Cancer Institute, Bethesda, MD) regarding the current status of senescence research, heterogeneity of therapy-induced senescence, current status of senotherapeutics and molecular biomarkers, a concept of “one-two punch” cancer therapy (consisting of therapeutics to induce tumor cell senescence followed by selective clearance of SnCs), and its integration with personalized adaptive tumor therapy. It also identifies key knowledge gaps and outlines future directions in this emerging field to improve treatment outcomes for cancer patients.