Search

Your search keyword '"Venitz, Jürgen"' showing total 166 results
Start Over Author "Venitz, Jürgen"
166 results on '"Venitz, Jürgen"'

17. PP-14, a Novel Structurally-Enhanced Antisickling Allosteric Hemoglobin Effector, Increases Oxygen Affinity and Disrupts Hemoglobin S Polymer Formation

Author

Safo, Martin K., primary, Pagare, Piyusha P, primary, Ghatge, Mohini, primary, Casu, Carla, primary, Ghiaccio, Valentina, primary, Anabaraonye, Nancy, primary, Xu, Xiaomeng, primary, Rivella, Stefano, primary, Hines, Patrick C., primary, Liu, Ke, primary, Zhang, Yan, primary, Venitz, Jürgen, primary, and Abdulmalik, Osheiza, primary

Published
2019
Full Text
View/download PDF

30. Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib

Author

Yarchoan Robert, Baum Caitlin E, English Bevin C, Liewehr David, Venzon David, Kummar Shivaani, Dahut William L, Kohn Elise C, Danesi Romano, Sissung Tristan M, Jain Lokesh, Giaccone Giuseppe, Venitz Jürgen, Price Douglas K, and Figg William D

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes. Methods Toxicities (≥ grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes. Results Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136). Conclusions This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib.

Published
2010
Full Text
View/download PDF

33. Design, Synthesis, and Biological Evaluation of Ester and Ether Derivatives of Antisickling Agent 5-HMF for the Treatment of Sickle Cell Disease

Author

Xu, Guoyan G., Pagare, Piyusha P., Ghatge, Mohini S., Safo, Ronni P., Gazi, Aheema, Chen, Qiukan, David, Tanya, Alabbas, Alhumaidi B., Musayev, Faik N., Venitz, Jürgen, Zhang, Yan, Safo, Martin K., and Abdulmalik, Osheiza

Abstract

Candidate drugs to counter intracellular polymerization of deoxygenated sickle hemoglobin (Hb S) continue to represent a promising approach to mitigating the primary cause of the pathophysiology associated with sickle cell disease (SCD). One such compound is the naturally occurring antisickling agent, 5-hydroxymethyl-2-furfural (5-HMF), which has been studied in the clinic for the treatment of SCD. As part of our efforts to develop novel efficacious drugs with improved pharmacologic properties, we structurally modified 5-HMF into 12 ether and ester derivatives. The choice of 5-HMF as a pharmacophore was influenced by a combination of its demonstrated attractive hemoglobin modifying and antisickling properties, well-known safety profiles, and its reported nontoxic major metabolites. The derivatives were investigated for their time- and/or dose-dependent effects on important antisickling parameters, such as modification of hemoglobin, corresponding changes in oxygen affinity, and inhibition of red blood cell sickling. The novel test compounds bound and modified Hb and concomitantly increased the protein affinity for oxygen. Five of the derivatives exhibited 1.5- to 4.0-fold higher antisickling effects than 5-HMF. The binding mode of the compounds with Hb was confirmed by X-ray crystallography and, in part, helps explain their observed biochemical properties. Our findings, in addition to the potential therapeutic application, provide valuable insights and potential guidance for further modifications of these (and similar) compounds to enhance their pharmacologic properties.

Published
2024
Full Text
View/download PDF

34. Pharmacokinetic profile analyses for inhaled drugs in humans using the lung delivery and disposition model.

Author

Raut, Anuja, Dhapare, Sneha, Venitz, Jürgen, and Sakagami, Masahiro

Subjects
DRUG analysis, LUNGS, DRUG abuse, MOMENTS method (Statistics), MUCOCILIARY system
Abstract

The kinetic clarification of lung disposition for inhaled drugs in humans via pharmacokinetic (PK) modeling aids in their development and regulation for systemic and local delivery, but remains challenging due to its multiplex nature. This study exercised our lung delivery and disposition kinetic model to derive the kinetic descriptors for the lung disposition of four drugs [calcitonin, tobramycin, ciprofloxacin and fluticasone propionate (FP)] inhaled via different inhalers from the published PK profile data. With the drug dose delivered to the lung (DTL) estimated from the corresponding γ‐scintigraphy or in vivo predictive cascade impactor data, the model‐based curve‐fitting and statistical moment analyses derived the rate constants of lung absorption (ka) and non‐absorptive disposition (knad). The ka values differed substantially between the drugs (0.05–1.00 h−1), but conformed to the lung partition‐based membrane diffusion except for FP, and were inhaler/delivery/deposition‐independent. The knad values also varied widely (0.03–2.32 h−1), yet appeared to be explained by the presence or absence of non‐absorptive disposition in the lung via mucociliary clearance, local tissue degradation, binding/sequestration and/or phagocytosis, and to be sensitive to differences in lung deposition. For FP, its ka value of 0.2 h−1 was unusually low, suggesting solubility/dissolution‐limited slow lung absorption, but was comparable between two inhaler products. Thus, the difference in the PK profile was attributed to differences in the DTL and the knad value, the latter likely originating from different aerosol sizes and regional deposition in the lung. Overall, this empirical, rather simpler model‐based analysis provided a quantitative kinetic understanding of lung absorption and non‐absorptive disposition for four inhaled drugs from PK profiles in humans. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

35. Design, Synthesis, and Biological Evaluation of Ester and Ether Derivatives of Antisickling Agent 5-HMF for the Treatment of Sickle Cell Disease

Author

Xu, Guoyan G., primary, Pagare, Piyusha P., additional, Ghatge, Mohini S., additional, Safo, Ronni P., additional, Gazi, Aheema, additional, Chen, Qiukan, additional, David, Tanya, additional, Alabbas, Alhumaidi B., additional, Musayev, Faik N., additional, Venitz, Jürgen, additional, Zhang, Yan, additional, Safo, Martin K., additional, and Abdulmalik, Osheiza, additional

Published
2017
Full Text
View/download PDF

39. Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib

Author

Jain, Lokesh, primary, Sissung, Tristan M, additional, Danesi, Romano, additional, Kohn, Elise C, additional, Dahut, William L, additional, Kummar, Shivaani, additional, Venzon, David, additional, Liewehr, David, additional, English, Bevin C, additional, Baum, Caitlin E, additional, Yarchoan, Robert, additional, Giaccone, Giuseppe, additional, Venitz, Jürgen, additional, Price, Douglas K, additional, and Figg, William D, additional

Published
2010
Full Text
View/download PDF

41. A Phase II Clinical Trial of Sorafenib in Androgen-Independent Prostate Cancer

Author

Dahut, William L., primary, Scripture, Charity, additional, Posadas, Edwin, additional, Jain, Lokesh, additional, Gulley, James L., additional, Arlen, Philip M., additional, Wright, John J., additional, Yu, Yunkai, additional, Cao, Liang, additional, Steinberg, Seth M., additional, Aragon-Ching, Jeanny B., additional, Venitz, Jürgen, additional, Jones, Elizabeth, additional, Chen, Clara C., additional, and Figg, William D., additional

Published
2008
Full Text
View/download PDF

46. Phase I clinical trial of oral 2-methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors

Author

Dahut, William L., primary, Lakhani, Nehal J., additional, Gulley, James L., additional, Arlen, Philip M., additional, Kohn, Elise C., additional, Kotz, Herbert, additional, McNally, Debbie, additional, Parr, Allyson, additional, Nguyen, Diana, additional, Yang, Sherry X., additional, Steinberg, Seth M., additional, Venitz, Jürgen, additional, Sparreboom, Alex, additional, and Figg, II, William, additional

Published
2006
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results