Drug-induced alterations in Mg2+ homoeostasis

2012 ◽  
Vol 123 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Anke L. Lameris ◽  
Leo A. Monnens ◽  
René J. Bindels ◽  
Joost G. J. Hoenderop
Keyword(s):  
Adverse Effects ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
Calcineurin Inhibitors ◽  
Drug Induced ◽  
Neuromuscular Abnormalities ◽  
Broad Variety ◽  
Epidermal Growth ◽  
High Doses ◽  
Insight Into

Magnesium (Mg2+) balance is tightly regulated by the concerted actions of the intestine, bone and kidneys. This balance can be disturbed by a broad variety of drugs. Diuretics, modulators of the EGFR (epidermal growth factor receptor), proton pump inhibitors, antimicrobials, calcineurin inhibitors and cytostatics may all cause hypomagnesaemia, potentially leading to tetany, seizures and cardiac arrhythmias. Conversely, high doses of Mg2+ salts, frequently administered as an antacid or a laxative, may lead to hypermagnesaemia causing various cardiovascular and neuromuscular abnormalities. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg2+ balance will indicate ways of prevention and treatment of these adverse effects and could potentially provide more insight into Mg2+ homoeostasis.

scholarly journals Molecular mechanisms of epidermal growth factor receptor overexpression in patients with cervical cancer

2011 ◽  
Vol 24 (5) ◽  
pp. 720-728 ◽  
Author(s):  
Marlies Schrevel ◽  
Arko Gorter ◽  
Sandra M Kolkman-Uljee ◽  
J Baptist M Z Trimbos ◽  
Gert Jan Fleuren ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
Epidermal Growth

scholarly journals Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S

2019 ◽  
Vol 10 (46) ◽  
pp. 10789-10801 ◽  
Author(s):  
Jonas Lategahn ◽  
Marina Keul ◽  
Philip Klövekorn ◽  
Hannah L. Tumbrink ◽  
Janina Niggenaber ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Binding Mode ◽  
Drug Resistant ◽  
X Ray ◽  
Covalent Inhibitors ◽  
Epidermal Growth ◽  
Resistant Mutants ◽  
Insight Into ◽  
Egfr T790m

We present inhibitors of drug resistant mutants of EGFR including T790M and C797S. In addition, we present the first X-ray crystal structures of covalent inhibitors in complex with C797S-mutated EGFR to gain insight into their binding mode.

BIOMIMETIC SYSTEMS SHED LIGHT ON ACTIN-BASED MOTILITY DOWN TO THE MOLECULAR SCALE

2009 ◽  
Vol 04 (01n02) ◽  
pp. 5-15 ◽  
Author(s):  
GUILLAUME ROMET-LEMONNE ◽  
EMMANUELE HELFER ◽  
VINCENT DELATOUR ◽  
BEATA BUGYI ◽  
MONTSERRAT BOSCH ◽  
...  
Keyword(s):  
Molecular Motors ◽  
Molecular Mechanisms ◽  
Directed Assembly ◽  
Cellular Processes ◽  
Self Organized ◽  
Filament Assembly ◽  
Physical Measurements ◽  
Minimum Number ◽  
Broad Variety ◽  
Insight Into

Cell motility, one of the modular activities of living cells, elicits the response of the cell to extra-cellular signals, to move directionally, feed, divide or transport materials. The combined actions of molecular motors and re-modeling of the cytoskeleton generate forces and movement. Here we describe mechanistic approaches of force and movement produced by site-directed assembly of actin filaments. The insight derived from a biochemical analysis of the protein machineries involved in "actin-based motile processes" like cell protrusions, invaginations, organelle propulsion, is used to build reconstituted assays that mimic cellular processes, using several protein machineries known to initiate filament assembly by different mechanisms. Reconstitution of complex self-organized systems presents a broad variety of interests. Reconstituting actin-based movement of a functionalized particle from a minimum number of pure proteins, first used to prove the general thermodynamic principles at work in motility, then was the basis for fully controlled physical measurements of forces produced by polymerization of actin against an obstacle and of the mechanical properties of the resulting polymer arrays. In addition, measurements at the mesoscopic scale (trajectories, velocity, polymer mechanics, fluorescence of specifically labeled components of the actin array, use of mutated proteins) can provide further insight into the molecular mechanisms underlying motility.

scholarly journals Structural insights into the activation mechanism of dynamin-like EHD ATPases

2017 ◽  
Vol 114 (22) ◽  
pp. 5629-5634 ◽  
Author(s):  
Arthur Alves Melo ◽  
Balachandra G. Hegde ◽  
Claudio Shah ◽  
Elin Larsson ◽  
J. Mario Isas ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
Cellular Membrane ◽  
Activation Mechanism ◽  
Gtpase Domain ◽  
Membrane Recruitment ◽  
Spin Resonance ◽  
Epidermal Growth ◽  
Electron Paramagnetic

Eps15 (epidermal growth factor receptor pathway substrate 15)-homology domain containing proteins (EHDs) comprise a family of dynamin-related mechano-chemical ATPases involved in cellular membrane trafficking. Previous studies have revealed the structure of the EHD2 dimer, but the molecular mechanisms of membrane recruitment and assembly have remained obscure. Here, we determined the crystal structure of an amino-terminally truncated EHD4 dimer. Compared with the EHD2 structure, the helical domains are 50° rotated relative to the GTPase domain. Using electron paramagnetic spin resonance (EPR), we show that this rotation aligns the two membrane-binding regions in the helical domain toward the lipid bilayer, allowing membrane interaction. A loop rearrangement in GTPase domain creates a new interface for oligomer formation. Our results suggest that the EHD4 structure represents the active EHD conformation, whereas the EHD2 structure is autoinhibited, and reveal a complex series of domain rearrangements accompanying activation. A comparison with other peripheral membrane proteins elucidates common and specific features of this activation mechanism.

Management of rash to erlotinib (E) and cetuximab (C): Results from the SERIES (Skin and Eye Reactions to Inhibitors of EGFR and kinaseS) clinic algorithm

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19556-19556
Author(s):  
N. V. Martin ◽  
V. Pacifico ◽  
S. E. Lai ◽  
A. Rademaker ◽  
S. Ortiz ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Calcineurin Inhibitors ◽  
Complete Response ◽  
Dose Modification ◽  
Management Algorithm ◽  
Topical Calcineurin Inhibitors ◽  
Best Response ◽  
Epidermal Growth ◽  
Intervention Trials ◽  
Rash Management

19556 Background: Rash develops in approximately 90% of patients (pts) treated with epidermal growth factor receptor inhibitors (EGFRIs) E and C, leading to significant physical/psychosocial discomfort and inconsistent therapy. This study characterizes outcomes of a rash management algorithm developed in the multidisciplinary dermatology-oncology SERIES clinic. Methods: Retrospective chart analysis was performed of pts with E and C rashes (n=45) who were treated with: oral tetracyclines (doxycycline or minocycline) bid and topical calcineurin inhibitors (pimecrolimus/ tacrolimus) or corticosteroids bid. After a baseline visit, pts were assessed at 2–4 week intervals and CTC graded (G). Management data, skin biopsies and photographs were evaluated. Response was defined as: Complete Response (CR) = severity decrease (decr) by 2G, Partial Response (PR) = 1G decr, Stable Disease (SD) = no G change, and Progressive Disease (PD) = increase by = 1G. Best response (BR) was defined as the patient’s best rash outcome at any point in time. Results: 43 out of 45 pts had evaluable data. Of 27 women and 16 men, mean age = 60 yrs (range 34–88), 60% received E and 40% C. For BR, 51% of patients had a CR, 42% had PR, 7% had SD, and 0% had PD. Age was related to BR (p=0.036), with median ages (in years) of 66, 57.5 and 48 for 22, 18 and 3 pts with CR, PR and SD respectively. BR was related to grade (p=0.045), with CR in 69% of G1 pts, 35% in G2 pts, and 54% in G3 pts. BR was not related to E or C (p=0.40). Dose modification was required in 8% (E) and 22% (C) and dose discontinuation in 0% (E) and 17% (C) pts. Conclusions: SERIES algorithm rash management demonstrates that combined oral tetracyclines, topical calcineurin inhibitors and corticosteroids result in improvement in a majority of subjects. The greater rate of dose modification/discontinuation with C supports the need for proactive/early intervention. Trials are underway to evaluate prophylactic therapies against rash to EGFRIs. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document