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  • br Discussion The membrane PVase activity components

    2020-09-15


    Discussion The membrane PVase activity components were discriminated in this work by pre-incubating with PMSF, mipafox, paraoxon or PMSF + mipafox to irreversibly inhibitPVase activity to discriminate the enzymatic components, (EPα, EPβ, EPγ and EPδ). The concentrations employed to discriminate the membrane enzymatic components of PVase activity were based on the kinetic properties reported by Mangas et al. (2012b; 2014). In those works, EPα was the activity resistant to PMSF, but was sensitive to mipafox or paraoxon. EPβ was resistant to mipafox, but sensitive to paraoxon or PMSF related to the known NTE. EPγ was resistant to paraoxon, but sensitive to mipafox or PMSF. EPδ was the resistant activity to all the inhibitors related to IRE. In the present work, the membrane PVase components were measured as the residual activity under conditions A, B, C and D shown in Table 2. Under condition D, only EPδ was measured. However, it was not possible to study isolated EPα, EPβ and EPγ because EPδ was resistant to all the used inhibitors. Nevertheless, they could be evaluated by studying the activity under condition A, B or C by taking into account that EPδ was included.
    Conflicts of interest
    Acknowledgements
    1. Introduction Serum cholinesterase (ChE) (or pseudocholinesterase [pChE]/butyrylcholinesterase) is a serine hydrolase that catalyses the hydrolysis of esters of choline [1]. pChE is produced in the liver and found in most tissues, with the exception of red blood cells [2]. Congenital pChE deficiency is a rare genetic abnormality which may lead to prolonged duration of action of muscle relaxants that are hydrolyzed by pChe [3]. The gene involved is located on chromosome 3 (3q26.1–q26.2) [4]. pChE deficiency is present in approximately 1 out of every 1,500 to 2,500 persons and it seems to affect male Caucasian Americans almost twice as often as their female counterparts [5]. Recently, ChE has been shown to modulate cellular proliferation and differentiation, suggesting a possible role in carcinogenesis [6], [7]. Serum ChE levels have been shown to be decreased in patients with various advanced cancers regardless of hepatic involvement [8]. One of the possible mechanisms underlying the lower ChE activity in cancer patients has been hypothesized to be its association with cancer-specific anorexia [9]. Another mechanism is its association with increased 873 activity which is known to promote the growth and metastasis in various cancers, including prostate cancer (CaP), via its M3 muscarinic receptor [10], [11]. Salvage radical prostatectomy (SRP) is performed for local failure after primary radiation therapy (RT) of CaP [12]. Five- and 10-year biochemical recurrence-free survival (BRFS) estimates range from 47% to 82% and from 28% to 53%, respectively; 10-year cancer-specific survival (CSS) and overall survival (OS) estimates range from 70% to 83% and from 54% to 89%, respectively. Pre-SRP prostate-specific antigen (PSA) levels and prostate biopsy Gleason score at time of recurrence are the strongest predictors of disease stage such as organ-confined disease status, progression, and CSS [13]. The aim of our study was to understand the role of serum ChE activity in patients with radiation-recurrent CaP who underwent SRP. To this end, we evaluated the association of preoperative serum ChE with clinicopathologic characteristics and outcomes in patients treated with SRP for biochemically recurrent, advanced CaP [14].
    2. Patients and methods
    3. Results
    4. Discussion We found that a decreased pretreatment serum ChE is associated with adverse pathologic features such as higher Gleason score and presence of positive lymph nodes after SRP. This is in agreement with Battisti et al. who found that it was significantly decreased in patients with Gleason ≥7. In patients with radiation-recurrent CaP, we found a significant proportion of patients with decreased pretreatment serum ChE had Gleason 10 (36%) [20]. Besides its association with adverse pathologic features, decreased serum ChE was also associated with lower body mass index. This may be due to the fact that in patients with decreased ChE nutritional status may be compromised as was shown in previous studies [7]. Also there is evidence supporting the influence of radiation on ChE as patients with radiation-recurrent cervical cancer (i.e., stages III and IV) had lower serum ChE [21]. In our study, the median serum ChE level was 6.94 kU/l, which is comparable to the reported value in patients with head and neck squamous cell carcinoma. Moreover, the authors of the latter study demonstrated that patients with squamous cell carcinoma had significantly lower serum ChE levels than healthy controls, suggesting that serum ChE is decreased in some cancer patients [22]. While this association with pathologic features is important, prediction of BCR is more important for clinical decision-making in patients with radiation-recurrent CaP [23].