Simultaneous Quantification of Total Antibody and Antibody-Conjugated Drug for XMT-1522 in Human Plasma Using Immunocapture-Liquid Chromatography/Mass Spectrometry

Publication date: Available online 11 June 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Ling Xu, Zhiling Zhang, Shengsheng Xu, Jian Xu, Zhongping John Lin, David LeeAbstractXMT-1522, an antibody-drug conjugate (ADC) currently in Phase I clinical development, represents the first Dolaflexin®-based, cleavable ADC with a high drug-antibody ratio (DAR). In this work, a novel immunocapture LC-MS/MS method was successfully developed for the simultaneous quantification of both total antibody and cleavable antibody-conjugated drug auristatin F-hydroxypropylamide (AF-HPA) in human plasma. This method utilized microwave-assisted enzymatic digestion for the total antibody and chemical release of the drug from ADC on a 96-well based immunocapture sample preparation platform. The total antibody and the conjugated drug AF-HPA were separated and subsequently quantified concurrently by LC-MS/MS. The linear range of the standard curve for total antibody was from 50 to 5000 ng/mL and for AF-HPA was from 3.3 to 330 ng/mL. The linearities showed R2 ≥ 0.993 for total antibody and R2 ≥ 0.996 for AF-HPA, respectively. The intra- and inter-day precision and accuracy were well within 15%. The validated method, with the characteristics of high efficiency, great selectivity, free of carryover, short LC-MS/MS time (˜3.5 min) and low sample volume (20 μl), was successfully applied for analyzing Phase 1 cancer patient samples.Graphi...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 23 July 2019Source: European UrologyAuthor(s): Patrick C. Walsh
Source: European Urology - Category: Urology & Nephrology Source Type: research
ConclusionsStandard gamble-based utilities in long-term survivors of PCa were much higher than those determined previously. The results indicate substantial human resilience: most PCa patients adapt to their health status over time even if they experience incomplete functional recovery and would not take risk in pursuit of better quality of life.Patient summaryWe elicited health utilities (measures of quality of life) among long-term survivors of prostate cancer using the most robust method. These were much higher than previously reported values that were based on theoretical scenarios or indirect methods. Long-term surviv...
Source: European Urology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 22 July 2019Source: European UrologyAuthor(s): Alec Paschalis, Beshara Sheehan, Ruth Riisnaes, Daniel Nava Rodrigues, Bora Gurel, Claudia Bertan, Ana Ferreira, Maryou B.K. Lambros, George Seed, Wei Yuan, David Dolling, Jon C. Welti, Antje Neeb, Semini Sumanasuriya, Pasquale Rescigno, Diletta Bianchini, Nina Tunariu, Suzanne Carreira, Adam Sharp, Wim OyenAbstractBackgroundProstate-specific membrane antigen (PSMA; folate hydrolase) prostate cancer (PC) expression has theranostic utility.ObjectiveTo elucidate PC PSMA expression and associate this with defective DNA damage repair (DDR).Design...
Source: European Urology - Category: Urology & Nephrology Source Type: research
ConclusionIntratumoral heterogeneity on MRI quantitatively displayed by histogram parameters can differentiate STS of different grades. Skewness and kurtosis on ER maps show the capacity.
Source: European Journal of Radiology - Category: Radiology Source Type: research
CONCLUSION: Taken together, the present findings suggested that matrine induced apoptosis and autophagy through down-regulating circ-104075 and Bcl-9 expression via inhibition of PI3K/AKT and Wnt-β-catenin pathways in glioma cells. The present study provides a foundation for further preclinical and clinical evaluations of matrine as a glioma therapy. PMID: 31112718 [PubMed - indexed for MEDLINE]
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
Abstract This paper provides an historical assessment of how the linear non-threshold (LNT) model became adopted as policy by the United States Environmental Protection Agency (US EPA) in 1975 [1] and how prior United States National Academy of Sciences (US NAS) radiation advisory panels may have affected this EPA decision. The paper highlights a generally unrecognized set of recommendations of the 1960 Biological Effect of Atomic Radiation [2] Genetics and Medical/Pathology Panels that did not support LNT for cancer risk assessment due to their judgements of its scientific limitations and unacceptable uncertainti...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
uml;rk E, Dörtbudak MB Abstract Although Doxorubicin (DOX) is a widespread drug used in the treatment of cancer, its clinical use is restricted due to its common side effects. In addition, administrating DOX with an antioxidant has recently become a new strategy in preventing the side effects of DOX. The protective effects of morin, a natural flavonoid, against DOX-induced liver and kidney damage in rats were investigated biochemically, immunohistochemically and histopathologically in this study. The experimental procedure was planned as 10 days, and 5 groups consisting of seven rats were formed. Morin was gi...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
Publication date: Available online 21 June 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Remco de Kock, Birgit Deiman, Raisa Kraaijvanger, Volkher ScharnhorstFor patients with suspected lung carcinoma, the analysis of circulating tumor DNA, obtained by liquid biopsy, has the potential to support cancer diagnosis and guide targeted therapy. To ensure sensitive and reproducible detection of circulating tumor DNA in routine clinical practice, a standardized (pre) analytical workflow is required. Plasma was obtained from patients and healthy volunteers. Using the QIAmp Circulating Nucleic Acid Kit (Qiagen Valencia...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research
Publication date: Available online 23 July 2019Source: Pathology - Research and PracticeAuthor(s): Ying-Nan Yang, Lu-Qin Bian, Xiao-Dong Ling, Cheng-Yuan Fang, Shu-Lin JiangAbstractRecent evidence highlights that microRNAs serve as crucial regulators of tumorigenesis, including non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression profile, clinical significance and biological role of miR-421 in NSCLC. The results showed that miR-421 expression was markedly increased in NSCLC tissues and cell lines. Further experimental data indicated that knockdown of miR-421 significantly inhibit...
Source: Pathology Research and Practice - Category: Pathology Source Type: research
ConclusionOur study demonstrates that up-regulated NID2 plays an important role in promoting the invasion and migration of GC cells and has a potential of being a novel biomarker for diagnosis, treatment and prognosis of GC in the future.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
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