Metabolism of Serum Albumin in Tumour-Bearing Rats

Unraveling the mysteries of serum albumin—more than just a serum protein

“…Additionally, a number of studies have proposed that tumors are a site of albumin catabolism (Hradec, 1958 ; Andersson et al, 1991 ; Schilling et al, 1992 ; Stehle et al, 1997 ). For instance, in a mouse sarcoma model (C57/RL6J) injected with 3 H-raffinose-labeled albumin, at least 2–3-fold greater levels of 3 H were observed in the lysosomes of tumors when compared with lysosomes of normal tissue (Andersson et al, 1991 ).…”

“…For instance, in a mouse sarcoma model (C57/RL6J) injected with 3 H-raffinose-labeled albumin, at least 2–3-fold greater levels of 3 H were observed in the lysosomes of tumors when compared with lysosomes of normal tissue (Andersson et al, 1991 ). Furthermore studies have demonstrated that albumin has a shorter half-life and a higher turnover in tumor-bearing mice, despite a compensatory increase in hepatic albumin synthesis, compared to non-tumor-bearing mice (Hradec, 1958 ). Hence, it has been suggested that tumors utilize albumin as a source of energy, by breaking down albumin into its component amino acids in lysosomes that are subsequently used by cancer cells for their accelerated growth (Stehle et al, 1997 ).…”

Kinetic studies of hyperimmune 7s globulins in allogenic rats bearing walker 256 tumors

“…This may represent faster turnover of all gamma globulins in tumor-bearing animals due t o increased serum protein catabolism. This effect has previously been shown t o be true of serum albumin catabolism in Walker 256-bearing rats (Jewell, 1966 ;Hradec, 1958).…”

Alkyl-Modified Oligonucleotides as Intercalating Vehicles for Doxorubicin Uptake via Albumin Binding

“…8 Albumin has favourable properties for therapeutic optimization including a long half-life, high abundance in plasma, a well-defined structure, and excellent binding properties for both endogenous and exogenous compounds. [9][10][11][12] Albumin is also of increasing importance for the delivery of cytotoxics since its uptake and metabolism is upregulated in tumor cells [13][14][15] and its accumulation in tumor neo-vasculature by the Enhanced Permeation Retention (EPR) effect. 16,17 The ability of intercalating cytotoxics to form strong physical complexes with double stranded oligonucleotides (dsODN) 18 has been studied as a potential prodrug strategy in oncology.…”

“…For example, pharmacokinetics may be enhanced by derivatization of the therapeutic or incorporation into synthetic carriers such as micelles, nanoparticles, and liposomes. − Natural particulates such as viruses and proteins are of increasing interest as delivery platforms for biologics and small drugs since they have the ability to pass through cell barriers, evade clearance by the body, and often have an established pharmacokinetic profile. − Human serum albumin (HSA) has been extensively studied and developed as a delivery platform toward this end with albumin-binding formulations such as Abraxane (HSA-bound paclitaxel) and Levemir (Myristic acid insulin conjugate) already in the clinic and Aldoxorubicin (HSA-bound doxorubicin) in Phase III clinical trials for soft tissue sarcoma . Albumin has favorable properties for therapeutic optimization including a long half-life, high abundance in plasma, a well-defined structure, and excellent binding properties for both endogenous and exogenous compounds. − Albumin is also of increasing importance for the delivery of cytotoxics since its uptake and metabolism is upregulated in tumor cells − and its accumulation in tumor neo-vasculature by the enhanced permeation retention (EPR) effect. , …”