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Thermally Induced Denaturing Energetics of Human Blood Plasma Albumin by Differential Scanning Calorimetry (DSC) as an Indicator for Breast Cancer Diagnosis in Female Patients

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Abstract

Cancerous invasion yields unusual metabolisms providing a significant amount of peptide albuminomes that modulate albumin stability via binding. The study aimed at the investigation of the thermal stability of human plasma albumin with breast cancer of various stages by means of differential scanning calorimetry (DSC). Blood plasma was drawn from 11 female breast cancer patients and 50 healthy volunteers of homogeneous demographics. Plasma samples and their albumin-enriched fractions were subjected to DSC scanning between 37 and 90°C at 5°C/min rate. For normal blood plasma, a characteristic signature of DSC tracing was observed. And, the deconvolution of DSC thermograms revealed the recognition of thermal transition of albumin. It was found that denaturing temperature of albumin increased with increasing breast cancer staging which implied the increase in albuminome/peptide abundance produced by cancerous invasion. The analysis of albumin denaturing energetics based on rational approximation of the simple Lumry-Eyring model demonstrated that thermal transition of free albumin and albuminome-bound form attained energetic levels expressed as apparent activation energy (Eapp ± s.e.) of 132.68 ± 14.21 and 46.76 ± 8.42 Kcal/mol corresponded to the schemes dominated by irreversible alteration and by reversible unfolding, respectively. Thus, Eapp value may indicate the degrees of cancerous invasion. It was proposed that Eapp may be used as an indicator to diagnose and assess the prognosis of breast cancer.

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Acknowledgements

Special thanks go to PSU Scientific Equipment Center, and Drug Delivery System Excellent Center, Faculty of Pharmaceutical Sciences for Lab facilities.

Funding

The authors are grateful to the Royal Golden Jubilee Ph. D. program for partial financial support and Thailand Research Fund as well as Prince of Songkla University for the co-funding research grant.

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Authors and Affiliations

  1. Drug Delivery System Excellent Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Science, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand

    Damrongsak Faroongsarng & Achara Raksawong

  2. Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand

    Somkiat Sunpaweravong

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  1. Damrongsak Faroongsarng
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  2. Somkiat Sunpaweravong
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  3. Achara Raksawong
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Correspondence to Damrongsak Faroongsarng.

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Faroongsarng, D., Sunpaweravong, S. & Raksawong, A. Thermally Induced Denaturing Energetics of Human Blood Plasma Albumin by Differential Scanning Calorimetry (DSC) as an Indicator for Breast Cancer Diagnosis in Female Patients. AAPS PharmSciTech 20, 146 (2019). https://doi.org/10.1208/s12249-019-1356-5

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