Expression of Fas, FasL, and Soluble Fas mRNA in Endomyocardial Biopsies of Human Cardiac Allografts

Pérez, Elizabeth; Shulzhenko, Natalia; Morgun, Andrey; Diniz, R.V.Z; Almeida, Dirceu Rodrigues; Musatti, Chloé C.; Gerbase‐DeLima, Maria

doi:10.1016/j.humimm.2006.02.037

Cited by 15 publications

(8 citation statements)

References 27 publications

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“…Along with these, Fas/FasL system has an important role in progressive renal disease and organ rejection in renal, cardiac and liver transplantation [35,36,37]. In a study done by Cappelesso et al, they have revealed that Fas −670GG genotype of the donor was associated with lower level of rejection episodes in renal transplant recipients [3].…”

Section: Discussionmentioning

confidence: 99%

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

Fadel

Elshamaa

Salah

et al. 2016

Transplant Immunology

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Section: Discussionmentioning

confidence: 99%

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

Fadel

Elshamaa

Salah

et al. 2016

Transplant Immunology

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“…A 426-bp Fas receptor fragment was amplified in 40 cycles using PCR Supermix (Invitrogen) primers 5 ¶-ACTTGGGGTG-GCTTTGTCTT-3 ¶ (forward) and 5 ¶-GGATGATAGTCTGAATTTTCTCTG-3 ¶ (reverse; ref. 20) and the following cycling conditions: 4 min at 94jC, then 40 cycles of 45 s at 94jC (denaturation), 30 s at 58.6jC (annealing), and 60 s at 72jC (extension), followed by 5 min at 72jC. A 251-bp fragment of the human glyceraldehyde-3-phosphatase dehydrogenase gene (GAPDH) was amplified with forward primer 5 ¶-CCATGTTCGTCATGGGTGTGAACCA-3 ¶ and reverse primer 5 ¶-GCCAGTAGAGGCAGGGATGATGTTC-3 ¶ (21) and used as loading control.…”

Section: Methodsmentioning

confidence: 99%

Combination of Measles Virus Virotherapy and Radiation Therapy Has Synergistic Activity in the Treatment of Glioblastoma Multiforme

Liu¹,

Sarkaria

Petell³

et al. 2007

Clinical Cancer Research

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Purpose: Glioblastoma multiforme is the most frequent primary brain tumor in adults and represents one of the most lethal malignancies with a median survival of 12-16 months.We have previously shown that an oncolytic measles virus derivative expressing soluble human carcinoembryonic antigen (MV-CEA) has significant antitumor activity against glioblastoma multiforme cell lines and xenografts. Radiation therapy (RT) represents one of the mainstays of glioma treatment. Here we tested the hypothesis that the combination of RTwith MV-CEA would have synergistic activity against gliomas. Experimental Design: 3-(4,5-Dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and clonogenic assays were used to test cytoxicity of the combination treatment in vivo. To examine the mechanism of synergy, one-step viral growth curves, terminal deoxyribonucleotidyl transferase^mediated dUTP nick end labeling (TUNEL) assays, and Western blot analyses were performed. In vivo assessment of synergistic antitumor activity was conducted in a U87 glioma model. Results: MTS and clonogenic assays showed a strong synergistic interaction between MV-CEA and RT in glioblastoma multiforme cells including both primary and established glioma lines. Furthermore, significant antitumor efficacy was observed in vivo in a subcuteneous U87 xenograph model. There was significant prolongation of survival (P = 0.001) in the combination treatment group as compared with single modality^or control-treated animals. One-step viral growth curves showed increased viral burst size by up to 2 log in MV/RTcombination^treated cells, as compared with single agent MV-CEA^treated glioma cells. Changes in CEA levels and expression of viral N and H protein were also consistent with increased viral production. Furthermore,TUNEL assays and Western blot analysis showed increase in apoptosis in MV/RT combination^treated cells. The pan-caspase inhibitor Z-VAD-FMK and the caspase-8 inhibitor Z-IETD-FMK, but not the caspase-9 inhibitor Z-IEHD-FMK, protected glioma cells from MV-CEA/ RT^induced cleavage of poly(ADP-ribose) polymerase (PARP), indicating that the apoptotic death in combination-treated cells is mostly mediated via the extrinsic caspase pathway. The Fas/Fas ligand interaction blocking antibody NOK-1blocked MV/RT^induced PARP cleavage whereas the Fas agonistic antibody CH11increased PARP cleavage in MV/RTcombination^treated cells. Reverse transcription-PCR, fluorescence-activated cell sorting analysis and immunohistochemistry showed up-regulation of Fas in combination-treated tumor in vitro and in vivo cells. Conclusions: There is synergy between MV-CEA and RT in vitro and in vivo. The synergistic effect of the combination seems to be due to increase in viral burst size and increase in apoptotic cell death. This latter effect is mostly mediated via the extrinsic caspase-8 pathway, activated via increased signaling through the Fas death receptor pathway.These results could have translational implications in glioma therapy.

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“…119 Increased mRNA levels of Fas and FasL are detected in human cardiac allografts during rejection. 120 Additionally, displaying a chimeric streptavidin-FasL (SA-FasL) protein artificially on cardiac vasculature prolongs graft survival in mice by selective deletion of alloreactive immune cells, predominantely CD4…”

Section: Functions Of Fasl and Fas In The Heartmentioning

confidence: 99%

The Role of FasL and Fas in Health and Disease

Ehrenschwender

Wajant

2009

Advances in Experimental Medicine and Biology

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The FS7-associated cell surface antigen (Fas, also named CD95, APO-1 or TNFRSF6) attracted considerable interest in the field of apoptosis research since its discovery in 1989. The groups of Shin Yonehara and Peter Krammer were the first reporting extensive apoptotic cell death induction upon treating cells with Fas-specific monoclonal antibodies.1,2 Cloning of Fas3 and its ligand,4,5 FasL (also known as CD178, CD95L or TNFSF6), laid the cornerstone in establishing this receptor-ligand system as a central regulator of apoptosis in mammals. Therapeutic exploitation of FasL-Fas-mediated cytotoxicity was soon an ambitous goal and during the last decade numerous strategies have been developed for its realization. In this chapter, we will briefly introduce essential general aspects of the FasL-Fas system before reviewing its physiological and pathophysiological relevance. Finally, FasL-Fas-related therapeutic tools and concepts will be addressed.

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Expression of Fas, FasL, and Soluble Fas mRNA in Endomyocardial Biopsies of Human Cardiac Allografts

Cited by 15 publications

References 27 publications

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

Combination of Measles Virus Virotherapy and Radiation Therapy Has Synergistic Activity in the Treatment of Glioblastoma Multiforme

The Role of FasL and Fas in Health and Disease

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