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957 results on '"Heinrich, P. C."'

53. Asciminib monotherapy in patients with CML-CP without BCR::ABL1T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results

Author

Mauro, Michael J., Hughes, Timothy P., Kim, Dong-Wook, Rea, Delphine, Cortes, Jorge E., Hochhaus, Andreas, Sasaki, Koji, Breccia, Massimo, Talpaz, Moshe, Ottmann, Oliver, Minami, Hironobu, Goh, Yeow Tee, DeAngelo, Daniel J., Heinrich, Michael C., Gómez-García de Soria, Valle, le Coutre, Philipp, Mahon, Francois-Xavier, Janssen, Jeroen J. W. M., Deininger, Michael, Shanmuganathan, Naranie, Geyer, Mark B., Cacciatore, Silvia, Polydoros, Fotis, Agrawal, Nithya, Hoch, Matthias, and Lang, Fabian

Abstract

Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10–200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population.

Published
2023
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72. Statin use is associated with improved overall survival in patients with melanoma

Author

Madison, Cecelia J., Heinrich, Michael C., Thompson, Reid F., and Yu, Wesley Y.

Abstract

Melanoma remains a leading cause of cancer morbidity and mortality. Recent literature suggests that statin use may improve outcomes in patients with cancer. In order to determine whether statins may improve survival in melanoma patients, we analyzed data from the Veterans Health Administration Corporate Data Warehouse that contains individually identifiable clinical and demographic information from the 1990s to the present for over 19 million individual veterans. We found that melanoma patients who were taking a statin had better 5-year OS when compared with veterans not taking statins. This relationship remained significant in a multivariate model (hazard ratio, 0.38; 95% confidence interval, 0.34–0.43 for statin user vs. nonuser). Importantly, this effect was much larger than the effect of statins in the general population and was remained after controlling for the use of other medications (beta-blocker), implying that statins may have a direct effect on survival in melanoma patients.

Published
2022
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73. Eine neubabylonische Edition eines mittelbabylonischen Nergal-Balaĝs (BM.35434)

Author

Heinrich, Adrian C.

Abstract

Published here for the first time, the Neo-Babylonian tablet BM.35434 sheds new light on the transmission history of the Sumero-Akkadian balaĝ-prayer a-gal-gal buru₁₄ su-su|| butuqtu muṭebbât ebūri “Flood that drowns the harvest” dedicated to Nergal, the god of pestilence and war. Due to its exceptional colophon, BM.35434 makes for an interesting case study in first-millennium scribal practices in the context of ritual lamenting and Emesal prayers: special points of interest are the use of older sign forms, the scribe and the family he comes from, the designation of the tablet as a copy of an “old large tablet” (dub.gal libir.ra), and the insertion of paratextual glosses that describe the state of preservation of the copied exemplar. An appendix contains copies and transliterations of hitherto unpublished fragments and joins that pertain to a-gal-gal buru₁₄ su-su.

Published
2022
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80. Imatinib-resistant gastrointestinal stromal tumors in the era of second- and third-line tyrosine kinase inhibitors: Does surgical resection have a role?

Author

Sutton, Thomas L., Walker, Brett S., Billingsley, Kevin G., Sheppard, Brett C., Corless, Christopher L., Heinrich, Michael C., and Mayo, Skye C.

Abstract

Imatinib resistance is associated with a poor prognosis in patients with gastrointestinal stromal tumors. Although novel tyrosine kinase inhibitors have improved outcomes in imatinib-resistant gastrointestinal stromal tumors, the role of resection remains unclear. We sought to investigate factors predictive of overall and progression-free survival in patients with imatinib-resistant gastrointestinal stromal tumors. A query of our prospectively maintained Comprehensive Cancer Center registry was performed from 2003 to 2019 for patients with imatinib-resistant gastrointestinal stromal tumors. Clinicopathologic characteristics and medical and surgical treatments were collected; overall survival and progression-free survival after imatinib-resistance were analyzed with Kaplan-Meier and Cox proportional hazards modeling. A total of 84 patients developed imatinib resistance at a median age of 59 years. Median time to imatinib resistance after diagnosis and overall survival after imatinib resistance was 50 and 51 months, respectively. After being diagnosed with imatinib resistance, 17 (20%) patients underwent resection. On multivariable analysis, resection after imatinib resistance was independently associated with improved progression-free survival (hazard ratio 0.50; P =.027) but not overall survival (hazard ratio 0.62; P =.215). Similar findings were found on subgroup analysis of patients treated with second-line sunitinib (n = 71). Long-term survival can be achieved in patients who develop imatinib-resistant gastrointestinal stromal tumors. Surgical resection of imatinib-resistant gastrointestinal stromal tumors is associated with improved progression-free survival and should be considered in selected patients. [ABSTRACT FROM AUTHOR]

Published
2021
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87. Insulated piggyBac vectors for insect transgenesis

Author

Horn Carsten, Li Xuelei, Heinrich Jörg C, Belikoff Esther J, Atapattu Asela, Sarkar Abhimanyu, Wimmer Ernst A, and Scott Maxwell J

Subjects
Biotechnology, TP248.13-248.65
Abstract

Abstract Background Germ-line transformation of insects is now a widely used method for analyzing gene function and for the development of genetically modified strains suitable for pest control programs. The most widely used transposable element for the germ-line transformation of insects is piggyBac. The site of integration of the transgene can influence gene expression due to the effects of nearby transcription enhancers or silent heterochromatic regions. Position effects can be minimized by flanking a transgene with insulator elements. The scs/scs' and gypsy insulators from Drosophila melanogaster as well as the chicken β-globin HS4 insulator function in both Drosophila and mammalian cells. Results To minimize position effects we have created a set of piggyBac transformation vectors that contain either the scs/scs', gypsy or chicken β-globin HS4 insulators. The vectors contain either fluorescent protein or eye color marker genes and have been successfully used for germ-line transformation of Drosophila melanogaster. A set of the scs/scs' vectors contains the coral reef fluorescent protein marker genes AmCyan, ZsGreen and DsRed that have not been optimized for translation in human cells. These marker genes are controlled by a combined GMR-3xP3 enhancer/promoter that gives particularly strong expression in the eyes. This is also the first report of the use of the ZsGreen and AmCyan reef fluorescent proteins as transformation markers in insects. Conclusion The insulated piggyBac vectors should protect transgenes against position effects and thus facilitate fine control of gene expression in a wide spectrum of insect species. These vectors may also be used for transgenesis in other invertebrate species.

Published
2006
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97. Interleukin-6

Author

Jose V. Castell, Andus, T., Kunz, D., and Heinrich, P. C.

Subjects
History and Philosophy of Science, General Neuroscience, General Biochemistry, Genetics and Molecular Biology
Published
2008

98. Asciminib, a First-in-Class STAMP Inhibitor, Provides Durable Molecular Response in Patients (pts) with Chronic Myeloid Leukemia (CML) Harboring the T315I Mutation: Primary Efficacy and Safety Results from a Phase 1 Trial

Author

Cortes, Jorge E., Hughes, Timothy P., Mauro, Michael J., Hochhaus, Andreas, Rea, Delphine, Goh, Yeow Tee, Janssen, Jeroen, Steegmann, Juan Luis, Heinrich, Michael C., Talpaz, Moshe, Etienne, Gabriel, Breccia, Massimo, Deininger, Michael W., le Coutre, Philipp D, Lang, Fabian, Aimone, Paola, Polydoros, Fotis, Cacciatore, Silvia, Stenson, Laura, and Kim, Dong-Wook

Published
2020
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