Whilst this does not constitute a formal mechanistic proof of the reaction, it does imply a reasonable one, and further that any alternative mechanism must have an overall lower energy barrier than this one.
This conjecture is based on similarity between sepsis-induced and tetrodotoxin-induced changes and therefore is not mechanistic proof of a role of the sodium channel.
The inhibition of metastasis-associated phenotypes, integrin-directed migration and invasion following Wnt-antagogist, WntC59 as well as β-catenin SiRNA provided mechanistic proof of concept for the involvement of this pathway in the progression of the disease and its clinical outcome.
Optimization of clinical trial design should include the choice of clinical end points which provide mechanistic proof-of-concept and also reflect clinical benefits (e.g., surrogates to assess increased collateral flow reserve, such as myocardial perfusion imaging).
In order to study the mechanisms-of-action (MOA) of JX-594 in humans, a mechanistic proof-of-concept clinical trial was performed at a low dose equivalent to ≤10% of the maximum-tolerated dose (MTD) in other clinical trials.
Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence.
Consequently, these investigators propose that Gadd45 α could act as a stress sensor following bacterial invasion of epithelial cells, even if a mechanistic proof is still lacking.
Perhaps one or several microorganisms, e.g., P. gingivalis, are capable of initiating synergetic interactions that ultimately result in the emergence of disease-provoking microbial community [ 7], however a mechanistic proof is lacking.
It must be noted, however, that the mechanistic proof was demonstrated in normal tissue, not in the tumour.
The biological applications presented do not provide real mechanistic insight and are proof-of-principle investigations showing that the method can be useful to address important biological questions.
Mechanistic studies recently provided the proof-of-concept that restoration of immunological tolerance can be achieved by haematopoietic SCT in chronic autoimmunity through eradication of the pathologic, immunologic memory and profound reconfiguration of the immune system, that is, immune 'resetting'resetting
