Synergistic effects of chlorambucil and TRAIL on apoptosis and proliferation of Raji cells
Authors: Y-Q Huang
J-X Guo
G-J Liu
J-X Pan
Y-H Zhou
Journal: European review for medical and pharmacological sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: TRAIL; Chlorambucil; apoptosis; proliferation; lymphoma
Affiliations: Department of Hematology, the 2nd Affiliated Hospital of Fujian Medical University, Fujian, China. .

Abstract:  Objective: Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) can induce the apoptosis of tumor cells, but leaving its effect on malignant lymphoma largely insignificant, as these tumors may develop drug resistance. Chlorambucil (CLB) had definitive treatment efficacy on low-malignant non-Hodgkin lymphoma (NHL), but with unclear efficacy on highly malignant Burkitt lymphoma. A study has been shown that CLB could enhance the sensitivity of chronic lymphatic leukemia cells against TRAIL. This work aims to investigate the effect of CLB combined with TRAIL on in vitro proliferation and apoptosis of Raji cells. Materials and methods: TRAIL (0, 20, 40 and 80 ng/ml) or CLB (0, 2.5 5 and 10 μM) was used to treat Raji cells. Cell counting kit 8 (CCK-8) was used to test proliferation whilst flow cytometry was employed to examine the apoptosis. The effect of TRAIL or CLB treatment on expression of death receptor 4 (DR4) and DR5 was tested. Combined treatment (80 ng/ml TRAIL and 10 μM CLB) was adopted for observing Raji cell proliferation and apoptosis. Results: Single treatment of TRAIL or CLB has weak effects of inducing apoptosis or inhibiting proliferation. TRAIL concentration has no significant effects on DR4/DR5 expression in Raji cells, whilst CLB treatment elevated those gene expressions. Combined treatment of TRAIL and CLB had more potent effects regarding cell proliferation inhibition or apoptosis induction compared to single treatment. Conclusions: TRAIL or CLB has weak inhibitor effects on Raji cell proliferation or induction of apoptosis. Via up-regulating DR4 and DR5 expression, CLB has synergistic effects with TRAIL to potentiate the apoptotic induction and proliferation inhibition role. 

Retracted: No

PubPeer comments:
 The paper is published in Vol. 7 No. 18 (2019): Sep 30 (Global Dermatology) of the Open Access Macedonian Journal of Medical Sciences . The whole issue is authored by the same group of people. 37 of the 39 papers in this issue lists Torello Lotti as an author. 37 39 list Aleksandra Vojvodic; 36 39 list Uwe Wollina; 19 39 list Petar Vojvodi; 19 39 list Michael Tirant; 18 39 list Massimo Fioranelli; 14 39 list Van Thuong Nguyen. Several of these papers are full of extraordinary claims. The publication of a bunch of papers, all by the same group of authors, in a supplemental issue of a journal raises the question whether these papers have been peer reviewed at all. Could the authors and editors please clarify if these are all peer reviewed papers? In this paper, the effect of microwaves on subcutaneous skin layers is studied. Figure 2 is presented as showing us the adipose tissue at time=0 ( Control ). Figure 5 represents adipose tissue at T=4, 2 months after treatment. ![file] The authors write:  *At time T4 (two months after treatment) the normal structure of the adipose tissue appear restored, as shown in semithin sections from epoxy resin embedding.* Figure 2 and 5, unexpectedly, appear to show an overlap. Could the authors please explain what happened here? ![file] , 
 Another concern about this paper. In this study, the authors treat a Vietnamese pig with the microwave device to melt away the fat, so to speak. In order to monitor the effects of the treatment the authors took biopsies at different time points for histology and EM photos. ![file] Figure 1 shows such a biopsy, and it appears to be 1.5 cm deep. That is a pretty deep wound. Was this study performed by a surgeon or veterinarian? Was anesthesia applied? Was the wound sutured? The authors write that  this study on the animal model was carried out in full compliance with international guidelines for safety and compliance with their use but there is no word on Animal Ethics Committee approval. Yet, they opened up the skin of the animal and took several deep biopsies to study. , 
 Retraction [30 September 2020] . Editor-in-Chief has retracted the following articles from the special issue Vol. 7 No. 18 (2019): Sep 30 (Global Dermatology): (1) DNA Waves and Their Applications in Biology - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889 oamjms.2019.767; (2) Recovery of Brain in Chick Embryos by Growing Second Heart and Brain - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889 oamjms.2019.777; (3) A Mathematical Model for the Signal of Death and Emergence of Mind Out of Brain in Izhikevich Neuron Model - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889 oamjms.2019.774; (4) A Black Hole at the Center of Earth Plays the Role of the Biggest System of Telecommunication for Connecting DNAs, Dark DNAs and Molecules of Water on 4+N- Dimensional Manifold - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889 oamjms.2019.776 (5) **New System Delivering Microwaves Energy for Inducing Subcutaneous Fat Reduction: In - Vivo Histological and Ultrastructural Evidence - Nicola Zerbinati et al.,** Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889 oamjms.2019.778. An internal investigation has raised sufficient evidence that they are not directly connected with the special issue Global Dermatology and contain inconsistent results. As such, we retract these articles from the literature and by guidelines and best editorial practices from the Committee on Publication Ethics. We apologize to our audience about this unfortunate situation. ,