scholarly journals Monomethyl Auristatin E Grafted-Liposomes to Target Prostate Tumor Cell Lines

2021 ◽  
Vol 22 (8) ◽  
pp. 4103
Author(s):  
Ariana Abawi ◽  
Xiaoyi Wang ◽  
Julien Bompard ◽  
Anna Bérot ◽  
Valentina Andretto ◽  
...  
Keyword(s):  
Drug Carriers ◽  
Prostate Tumor ◽  
Drug Conjugates ◽  
Lipid Derivative ◽  
Target Membrane ◽  
Liposome Fusion ◽  
Prostate Tumor Cells ◽  
Nih 3T3 ◽  
Prostate Tumor Cell ◽  
Key Parameter

Novel nanomedicines have been engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or short half-life. Lipid-based carriers such as liposomes represent one of the most advanced classes of drug delivery systems. A Monomethyl Auristatin E (MMAE) warhead was grafted on a lipid derivative and integrated in fusogenic liposomes, following the model of antibody drug conjugates. By modulating the liposome composition, we designed a set of particles characterized by different membrane fluidities as a key parameter to obtain selective uptake from fibroblast or prostate tumor cells. Only the fluid liposomes made of palmitoyl-oleoyl-phosphatidylcholine and dioleoyl-phosphatidylethanolamine, integrating the MMAE-lipid derivative, showed an effect on prostate tumor PC-3 and LNCaP cell viability. On the other hand, they exhibited negligible effects on the fibroblast NIH-3T3 cells, which only interacted with rigid liposomes. Therefore, fluid liposomes grafted with MMAE represent an interesting example of drug carriers, as they can be easily engineered to promote liposome fusion with the target membrane and ensure drug selectivity.

scholarly journals Activin βC-Subunit Heterodimers Provide a New Mechanism of Regulating Activin Levels in the Prostate

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4410-4419 ◽  
Author(s):  
Sally L. Mellor ◽  
Emma M. A. Ball ◽  
Anne E. O’Connor ◽  
Jean-François Ethier ◽  
Mark Cranfield ◽  
...  
Keyword(s):  
Biological Function ◽  
Regulatory Mechanism ◽  
Tumor Cell Line ◽  
Activin A ◽  
Prostate Tumor ◽  
Differentiation Factors ◽  
Potent Growth ◽  
Prostate Tumor Cells ◽  
Human Prostate Tumor ◽  
Prostate Tumor Cell

Activins are formed by dimerization of β-subunits and, as members of the TGF-β superfamily, have diverse roles as potent growth and differentiation factors. As the biological function of the activin C homodimer (βC-βC) is unknown, we sought to compare activin A (βA-βA), B (βB-βB), and C homodimer bioactivities and to investigate the consequences of activin βC-subunit overexpression in prostate tumor cells. Exogenous activin A and B homodimers inhibited cell growth and activated activin-responsive promoters. In contrast, the activin C homodimer was unable to elicit these responses. We previously showed that the activin βC-subunit heterodimerized with activin βAin vitro to form activin AC. Therefore, we hypothesize that the activin βC-subunit regulates the levels of bioactive activin A by the formation of activin AC heterodimers. To test this hypothesis, we measured activin AC heterodimer production using a novel specific two-site ELISA that we developed for this purpose. In the PC3 human prostate tumor cell line, activin βC-subunit overexpression increased activin AC heterodimer levels, concomitantly reduced activin A levels, and decreased activin signaling. Overall, these data are consistent with a role for the activin βC-subunit as a regulatory mechanism to reduce activin A secretion via intracellular heterodimerization.

scholarly journals Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 30
Author(s):  
Andrew T. Lucas ◽  
Amber Moody ◽  
Allison N. Schorzman ◽  
William C. Zamboni
Keyword(s):  
Immune System ◽  
Market Value ◽  
Therapeutic Index ◽  
Drug Carriers ◽  
Antibody Engineering ◽  
Antibody Drug Conjugates ◽  
Success Stories ◽  
Drug Conjugates ◽  
Early Success ◽  
Antibody Drug

Antibody-drug conjugates (ADCs) appear to be in a developmental boom, with five FDA approvals in the last two years and a projected market value of over $4 billion by 2024. Major advancements in the engineering of these novel cytotoxic drug carriers have provided a few early success stories. Although the use of these immunoconjugate agents are still in their infancy, valuable lessons in the engineering of these agents have been learned from both preclinical and clinical failures. It is essential to appreciate how the various mechanisms used to engineer changes in ADCs can alter the complex pharmacology of these agents and allow the ADCs to navigate the modern-day therapeutic challenges within oncology. This review provides a global overview of ADC characteristics which can be engineered to alter the interaction with the immune system, pharmacokinetic and pharmacodynamic profiles, and therapeutic index of ADCs. In addition, this review will highlight some of the engineering approaches being explored in the creation of the next generation of ADCs.

scholarly journals Relationships between proto-oncogene expression and apoptosis induced by anticancer drugs in human prostate tumor cells

1995 ◽  
Vol 1270 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Birandra K. Sinha ◽  
Hiroyuki Yamazaki ◽  
Helen M. Eliot ◽  
Erasmus Schneider ◽  
Markus M. Borner ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Anticancer Drugs ◽  
Prostate Tumor ◽  
Human Prostate ◽  
Oncogene Expression ◽  
Prostate Tumor Cells ◽  
Human Prostate Tumor

scholarly journals Cytoplasmic retention of protein tyrosine kinase 6 promotes growth of prostate tumor cells

Cell Cycle ◽  
2010 ◽  
Vol 9 (20) ◽  
pp. 4190-4199 ◽  
Author(s):  
Patrick M. Brauer ◽  
Yu Zheng ◽  
Lin Wang ◽  
Angela Tyner
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Cells ◽  
Protein Tyrosine Kinase ◽  
Prostate Tumor ◽  
Protein Tyrosine ◽  
Prostate Tumor Cells

A constitutively active ErbB4 mutant inhibits drug-resistant colony formation by the DU-145 and PC-3 human prostate tumor cell lines

2003 ◽  
Vol 192 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Eric E Williams ◽  
Laurie J Trout ◽  
Richard M Gallo ◽  
Sarah E Pitfield ◽  
Ianthe Bryant ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Colony Formation ◽  
Prostate Tumor ◽  
Human Prostate ◽  
Drug Resistant ◽  
Tumor Cell Lines ◽  
Human Prostate Tumor ◽  
Prostate Tumor Cell ◽  
Constitutively Active
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