scholarly journals Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry–Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors

2019 ◽  
Vol 20 (20) ◽  
pp. 4984 ◽  
Author(s):  
Stephanie J. Gros ◽  
Stefan G. Holland-Cunz ◽  
Claudiu T. Supuran ◽  
Olivier Braissant

We present a novel approach to a personalized therapeutic concept for solid tumors. We illustrate this on a rare childhood tumor for which only a generalized treatment concept exists using carbonic anhydrase IX and aquaporin 1 inhibitors. The use of microcalorimetry as a refined in vitro method for evaluation of drug susceptibility in organotypic slice culture has not previously been established. Rapid microcalorimetric drug response assessment can refine a general treatment concept when it is applied in cases in which tumors do not respond to conventional chemo-radiation treatment. For solid tumors, which do not respond to classical treatment, and especially for rare tumors without an established protocol rapid microcalorimetric drug response testing presents an elegant novel approach to test alternative therapeutic approaches. While improved treatment concepts have led to improved outcome over the past decades, the prognosis of high risk disease is still poor and rethinking of clinical trial design is necessary. A small patient population combined with the necessity to assess experimental therapies for rare solid tumors rather at the time of diagnosis than in relapsed or refractory patients provides great challenges. The possibility to rapidly compare established protocols with innovative therapeutics presents an elegant novel approach to refine and personalize treatment.

2020 ◽  
Vol 43 (7) ◽  
pp. 484-490 ◽  
Author(s):  
Paul C. McDonald ◽  
Stephen Chia ◽  
Philippe L. Bedard ◽  
Quincy Chu ◽  
Michael Lyle ◽  
...  

2004 ◽  
Vol 171 (4S) ◽  
pp. 206-207 ◽  
Author(s):  
Hideki Mukouyama ◽  
Masahiro Yao ◽  
David B. Seligson ◽  
John S. Lam ◽  
Yoji Nagashima ◽  
...  

2019 ◽  
Vol 78 (12) ◽  
pp. 1081-1088
Author(s):  
Rati Chkheidze ◽  
Patrick J Cimino ◽  
Kimmo J Hatanpaa ◽  
Charles L White ◽  
Manuel Ferreira ◽  
...  

Abstract Clear cell, microcytic, and angiomatous meningiomas are 3 vasculature-rich variants with overlapping morphological features but different prognostic and treatment implications. Distinction between them is not always straightforward. We compared the expression patterns of the hypoxia marker carbonic anhydrase IX (CA-IX) in meningiomas with predominant clear cell (n = 15), microcystic (n = 9), or angiomatous (n = 11) morphologies, as well as 117 cases of other World Health Organization recognized histological meningioma variants. Immunostaining for SMARCE1 protein, whose loss-of-function has been associated with clear cell meningiomas, was performed on all clear cell meningiomas, and selected variants of meningiomas as controls. All clear cell meningiomas showed absence of CA-IX expression and loss of nuclear SMARCE1 expression. All microcystic and angiomatous meningiomas showed diffuse CA-IX immunoreactivity and retained nuclear SMARCE1 expression. In other meningioma variants, CA-IX was expressed in a hypoxia-restricted pattern and was highly associated with atypical features such as necrosis, small cell change, and focal clear cell change. In conclusion, CA-IX may serve as a useful diagnostic marker in differentiating clear cell, microcystic, and angiomatous meningiomas.


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