scholarly journals Classic Hodgkin Lymphoma Refractory for ABVD Treatment Is Characterized by Pathologically Activated Signal Transduction Pathways as Revealed by Proteomic Profiling

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 247
Author(s):  
Bent Honoré ◽  
Maja Dam Andersen ◽  
Diani Wilken ◽  
Peter Kamper ◽  
Francesco d’Amore ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Hodgkin Lymphoma ◽  
Bioinformatic Analysis ◽  
Signal Transduction Pathways ◽  
Refractory Disease ◽  
Label Free ◽  
Proteomic Profiling ◽  
Classic Hodgkin Lymphoma ◽  
Treatment Refractory ◽  
Biological Differences

In classic Hodgkin lymphoma (cHL), the tumour microenvironment (TME) is of major pathological relevance. The paucity of neoplastic cells makes it important to study the entire TME when searching for prognostic biomarkers. Cure rates in cHL have improved markedly over the last several decades, but patients with primary refractory disease still show inferior survival. We performed a proteomic comparison of pretreatment tumour tissue from ABVD treatment-refractory versus ABVD treatment-sensitive cHL patients, in order to identify biological differences correlating with treatment outcome. Formalin-fixed paraffin-embedded tumour tissues from 36 patients with cHL, 15 with treatment-refractory disease, and 21 with treatment-sensitive disease, were processed for proteomic investigation. Label-free quantification nano liquid chromatography tandem mass spectrometry was performed on the tissues. A total of 3920 proteins were detected and quantified between the refractory and sensitive groups. This comparison revealed several subtle but significant differences in protein expression which could identify subcluster characteristics of the refractory group. Bioinformatic analysis of the biological differences indicated that a number of pathologically activated signal transduction pathways are disturbed in ABVD treatment-refractory cHL.

scholarly journals Trends in postrelapse survival in classic Hodgkin lymphoma patients after experiencing therapy failure following auto-HCT

2020 ◽  
Vol 4 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Talha Badar ◽  
Narendranath Epperla ◽  
Aniko Szabo ◽  
Steven Borson ◽  
John Vaughn ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Future Research ◽  
Refractory Disease ◽  
Novel Therapies ◽  
Therapy Failure ◽  
Classic Hodgkin Lymphoma ◽  
Key Points ◽  
Effective Use

Key Points PR-OS of cHL patients has improved in recent years, likely due to incorporation of novel therapies and more effective use of allo-HCT. Future research should focus on earlier integration of novel therapies for patients with refractory disease to improve outcomes further.

Signal-regulated oxidation of proteins via MICAL

2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert
Keyword(s):  
Signal Transduction ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Redox Regulation ◽  
Signal Transduction Pathways ◽  
Cellular Functions ◽  
Intracellular Signals ◽  
Amino Acid Side Chains ◽  
Specific Receptors ◽  
Sulfur Containing

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.

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