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For: Viard-Leveugle I, Veyrenc S, French LE, Brambilla C, Brambilla E. Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma. J Pathol 2003;201:268-77. [PMID: 14517844 DOI: 10.1002/path.1428] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

For:	Viard-Leveugle I, Veyrenc S, French LE, Brambilla C, Brambilla E. Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma. J Pathol 2003;201:268-77. [PMID: 14517844 DOI: 10.1002/path.1428] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Number

Cited by Other Article(s)

Papadaki MA, Papadaki E, Chatziavraam S, Aggouraki D, Michaelidou K, Fotsitzoudis C, Vassilakopoulou M, Mavroudis D, Agelaki S. Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer. Cancers (Basel) 2024;16:2927. [PMID: 39272785 PMCID: PMC11393959 DOI: 10.3390/cancers16172927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 09/15/2024] Open

Huang M, Wang Y, Fang L, Liu C, Feng F, Liu L, Sun C. T cell senescence: a new perspective on immunotherapy in lung cancer. Front Immunol 2024;15:1338680. [PMID: 38415245 PMCID: PMC10896971 DOI: 10.3389/fimmu.2024.1338680] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/30/2024] [Indexed: 02/29/2024] Open

James A, Akash K, Sharma A, Bhattacharyya S, Sriamornsak P, Nagraik R, Kumar D. Himalayan flora: targeting various molecular pathways in lung cancer. Med Oncol 2023;40:314. [PMID: 37787816 DOI: 10.1007/s12032-023-02171-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 08/21/2023] [Indexed: 10/04/2023]

Khodayari Moez E, Warkentin MT, Brhane Y, Lam S, Field JK, Liu G, Zulueta JJ, Valencia K, Mesa-Guzman M, Nialet AP, Atkar-Khattra S, Davies MPA, Grant B, Murison K, Montuenga LM, Amos CI, Robbins HA, Johansson M, Hung RJ. Circulating proteome for pulmonary nodule malignancy. J Natl Cancer Inst 2023;115:1060-1070. [PMID: 37369027 PMCID: PMC10483334 DOI: 10.1093/jnci/djad122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 05/29/2023] [Accepted: 06/22/2023] [Indexed: 06/29/2023] Open

Abstract

BACKGROUND

Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a major challenge. We conducted one of the first systematic investigations of circulating protein markers to differentiate malignant from benign screen-detected pulmonary nodules.

METHODS

Based on 4 international low-dose computed tomography screening studies, we assayed 1078 protein markers using prediagnostic blood samples from 1253 participants based on a nested case-control design. Protein markers were measured using proximity extension assays, and data were analyzed using multivariable logistic regression, random forest, and penalized regressions. Protein burden scores (PBSs) for overall nodule malignancy and imminent tumors were estimated.

RESULTS

We identified 36 potentially informative circulating protein markers differentiating malignant from benign nodules, representing a tightly connected biological network. Ten markers were found to be particularly relevant for imminent lung cancer diagnoses within 1 year. Increases in PBSs for overall nodule malignancy and imminent tumors by 1 standard deviation were associated with odds ratios of 2.29 (95% confidence interval: 1.95 to 2.72) and 2.81 (95% confidence interval: 2.27 to 3.54) for nodule malignancy overall and within 1 year of diagnosis, respectively. Both PBSs for overall nodule malignancy and for imminent tumors were substantially higher for those with malignant nodules than for those with benign nodules, even when limited to Lung Computed Tomography Screening Reporting and Data System (LungRADS) category 4 (P < .001).

CONCLUSIONS

Circulating protein markers can help differentiate malignant from benign pulmonary nodules. Validation with an independent computed tomographic screening study will be required before clinical implementation.

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Affiliation(s)

Elham Khodayari Moez Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada
Matthew T Warkentin Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
Yonathan Brhane Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada
Stephen Lam Integrative Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada
John K Field Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
Geoffrey Liu Computational Biology and Medicine Program, Princess Margaret Cancer Center, Toronto, ON, Canada
Javier J Zulueta Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai Morningside Hospital, Icahn School of Medicine, New York, NY, USA
Karmele Valencia Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Madrid, Spain
Miguel Mesa-Guzman Thoracic Surgery Department, Clínica Universidad de Navarra, Pamplona, Spain
Andrea Pasquier Nialet Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Madrid, Spain
Sukhinder Atkar-Khattra Integrative Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada
Michael P A Davies Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
Benjamin Grant Computational Biology and Medicine Program, Princess Margaret Cancer Center, Toronto, ON, Canada
Kiera Murison Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada
Luis M Montuenga Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Madrid, Spain
Christopher I Amos Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
Hilary A Robbins Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France
Mattias Johansson Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France
Rayjean J Hung Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

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Smok-Kalwat J, Mertowska P, Mertowski S, Smolak K, Kozińska A, Koszałka F, Kwaśniewski W, Grywalska E, Góźdź S. The Importance of the Immune System and Molecular Cell Signaling Pathways in the Pathogenesis and Progression of Lung Cancer. Int J Mol Sci 2023;24:1506. [PMID: 36675020 PMCID: PMC9861992 DOI: 10.3390/ijms24021506] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/04/2023] [Accepted: 01/08/2023] [Indexed: 01/13/2023] Open

Meijer JJ, Leonetti A, Airò G, Tiseo M, Rolfo C, Giovannetti E, Vahabi M. Small cell lung cancer: Novel treatments beyond immunotherapy. Semin Cancer Biol 2022;86:376-385. [PMID: 35568295 DOI: 10.1016/j.semcancer.2022.05.004] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/03/2022] [Accepted: 05/07/2022] [Indexed: 11/23/2022]

Sulejmani O, Grunewald L, Andersch L, Schwiebert S, Klaus A, Winkler A, Astrahantseff K, Eggert A, Henssen AG, Schulte JH, Anders K, Künkele A. Inhibiting Lysine Demethylase 1A Improves L1CAM-Specific CAR T Cell Therapy by Unleashing Antigen-Independent Killing via the FAS-FASL Axis. Cancers (Basel) 2021;13:cancers13215489. [PMID: 34771652 PMCID: PMC8583435 DOI: 10.3390/cancers13215489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/18/2021] [Accepted: 10/22/2021] [Indexed: 11/16/2022] Open

Abstract

Simple Summary

Solid tumor cells can lose or heterogeneously express antigens to become resistant to chimeric antigen receptor (CAR) T cell therapy. Here, we explore whether epigenetic manipulation to unleash antigen-independent killing mechanisms can overcome this hurdle. KDM1A is overexpressed in many cancers and removes lysine methylation on histones that keeps the DNA firmly packed to selectively activate or repress gene activity, depending on the specific lysine target. KDM1A also regulates the expression of nonhistone proteins. We inhibited KDM1A in the childhood tumor, neuroblastoma, to increase FAS expression on tumor cells. The FAS receptor can be triggered to induce cell death when bound by the FAS ligand on CAR and other activated T cells present in the tumor environment, even if the tumor cells lack the target antigen. FAS upregulation via KDM1A inhibition sensitized neuroblastoma cells to FAS-FASL-mediated killing and augmented CAR T cell therapy against antigen-poor or even antigen-negative neuroblastoma.

Abstract

Chimeric antigen receptor (CAR) T cell therapy has emerged as a promising treatment strategy, however, therapeutic success against solid tumors such as neuroblastoma remains modest. Recurrence of antigen-poor tumor variants often ultimately results in treatment failure. Using antigen-independent killing mechanisms such as the FAS receptor (FAS)-FAS ligand (FASL) axis through epigenetic manipulation may be a way to counteract the escape achieved by antigen downregulation. Analysis of public RNA-sequencing data from primary neuroblastomas revealed that a particular epigenetic modifier, the histone lysine demethylase 1A (KDM1A), correlated negatively with FAS expression. KDM1A is known to interact with TP53 to repress TP53-mediated transcriptional activation of genes, including FAS. We showed that pharmacologically blocking KDM1A activity in neuroblastoma cells with the small molecule inhibitor, SP-2509, increased FAS cell-surface expression in a strictly TP53-dependent manner. FAS upregulation sensitized neuroblastoma cells to FAS-FASL-dependent killing and augmented L1CAM-directed CAR T cell therapy against antigen-poor or even antigen-negative tumor cells in vitro. The improved therapeutic response was abrogated when the FAS-FASL interaction was abolished with an antagonistic FAS antibody. Our results show that KDM1A inhibition unleashes an antigen-independent killing mechanism via the FAS-FASL axis to make tumor cell variants that partially or totally suppress antigen expression susceptible to CAR T cell therapy.

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Affiliation(s)

Ornela Sulejmani Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.)
Laura Grunewald Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.)
Lena Andersch Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.)
Silke Schwiebert Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.)
Anika Klaus Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.)
Annika Winkler Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.)
Kathy Astrahantseff Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.)
Angelika Eggert Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.) German Cancer Consortium (DKTK), 10117 Berlin, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Anton G. Henssen Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.) German Cancer Consortium (DKTK), 10117 Berlin, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany Experimental and Clinical Research Center, Lindenberger Weg 80, 13125 Berlin, Germany
Johannes H. Schulte Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.) German Cancer Consortium (DKTK), 10117 Berlin, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Kathleen Anders German Cancer Consortium (DKTK), 10117 Berlin, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Annette Künkele Department of Pediatric Oncology and Hematology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universiät zu Berlin, 10353 Berlin, Germany; (O.S.); (L.G.); (L.A.); (S.S.); (A.K.); (A.W.); (K.A.); (A.E.); (A.G.H.); (J.H.S.) German Cancer Consortium (DKTK), 10117 Berlin, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany Correspondence: ; Tel.: +49-(0)30-450-616178

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Apoptosis-Inducing TNF Superfamily Ligands for Cancer Therapy. Cancers (Basel) 2021;13:cancers13071543. [PMID: 33801589 PMCID: PMC8036978 DOI: 10.3390/cancers13071543] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/21/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open

Vacchelli E, Galluzzi L, Rousseau V, Rigoni A, Tesniere A, Delahaye N, Schlemmer FDR, Menger L, Sukkurwala AQ, Adjemian S, Martins I, Michaud M, Dunant A, Kepp O, Brambilla E, Soria JC, Zitvogel L, Kroemer G. Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer. Oncoimmunology 2021;1:271-278. [PMID: 22737602 PMCID: PMC3382853 DOI: 10.4161/onci.18684] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open

Harnessing the Immune System to Tackle Small Cell Lung Cancer. ACTA ACUST UNITED AC 2020;26:502-506. [PMID: 33298721 DOI: 10.1097/ppo.0000000000000490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]

miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling. Cell Death Dis 2020;11:785. [PMID: 32963220 PMCID: PMC7508872 DOI: 10.1038/s41419-020-02997-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 08/31/2020] [Accepted: 09/04/2020] [Indexed: 02/07/2023]

Lin YM, Chen ML, Chen CL, Yeh CM, Sung WW. Overexpression of EIF5A2 Predicts Poor Prognosis in Patients with Oral Squamous Cell Carcinoma. Diagnostics (Basel) 2020;10:436. [PMID: 32605067 PMCID: PMC7400414 DOI: 10.3390/diagnostics10070436] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 06/17/2020] [Accepted: 06/25/2020] [Indexed: 12/20/2022] Open

Wan Mohd Tajuddin WNB, Lajis NH, Abas F, Othman I, Naidu R. Mechanistic Understanding of Curcumin's Therapeutic Effects in Lung Cancer. Nutrients 2019;11:E2989. [PMID: 31817718 PMCID: PMC6950067 DOI: 10.3390/nu11122989] [Citation(s) in RCA: 105] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/22/2019] [Accepted: 11/30/2019] [Indexed: 12/24/2022] Open

Yadegari M, Sellami M, Riahy S, Mirdar S, Hamidian G, Saeidi A, Abderrahman AB, Hackney AC, Zouhal H. Supplementation of Adiantum capillus-veneris Modulates Alveolar Apoptosis under Hypoxia Condition in Wistar Rats Exposed to Exercise. ACTA ACUST UNITED AC 2019;55:medicina55070401. [PMID: 31340610 PMCID: PMC6681305 DOI: 10.3390/medicina55070401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 07/13/2019] [Accepted: 07/18/2019] [Indexed: 11/16/2022]

Abstract

Background and Objectives: Several studies have reported that some conditions such as exercise and hypoxia induce DNA damage and dysfunction and apoptosis. Some plant foods contain numerous bioactive compounds and anti-inflammatory properties that can help fight DNA damage. Therefore, the current study evaluated the effect of supplementation of Adiantum capillus-veneris (ACV) extract on Bax/B-cell lymphoma 2 (Bcl-2) ratio apoptotic index and remodeling of pulmonary alveolar epithelial cells in lung tissue of healthy Wistar rats during stressful conditions (hypoxia). Materials and Methods: Twenty-seven Wistar male rats (four-week old, 72 ± 9 g) were randomly assigned into three groups: normoxic, sedentary, and not-supplemented (NG, n = 9); exercise and hypoxia and not-supplemented (HE, n = 9); and exercise and hypoxia and supplemented group (HS, n = 9). The NG remained sedentary in the normoxia environment for nine weeks. The HE group participated in a high-intensity (IT) program for six weeks, then remained sedentary in the hypoxia environment for three weeks. The low-pressure chamber simulated a ~2800 M altitude 24 h/d. HS participated in IT, then entered and remained sedentary in the hypoxia environment for three weeks, and they consumed 500 mg per kg of body weight ACV extract. Results: The Bax/Bcl-2 ratio of the HE group increased significantly (+50.27%, p ≤ 0.05), the average number of type I pneumocytes was reduced significantly (−18.85%, p ≤ 0.05), and the average number of type II pneumocytes was increased significantly (+14.69%, p ≤ 0.05). Also, after three weeks of consuming the ACV extract, the HS group in comparison with the HE group had their Bax/Bcl-2 ratio reduced significantly (−24.27%, p ≤ 0.05), the average number of type I pneumocytes increased significantly (+10.15%, p ≤ 0.05), and the average number of type II pneumocytes reduced significantly (−7.18%, p ≤ 0.05). Conclusion: The findings show that after three weeks of hypoxia following six weeks of high-intensity interval training in Wistar rats, the Bax/Bcl-2 ratio and the number of type II pneumocytes were increased and the number of type I pneumocytes was reduced significantly. These results strongly suggest that an apoptosis state was induced in the lung parenchyma, and consuming ACV extract modulated this state.

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Tian Y, Zhai X, Han A, Zhu H, Yu J. Potential immune escape mechanisms underlying the distinct clinical outcome of immune checkpoint blockades in small cell lung cancer. J Hematol Oncol 2019;12:67. [PMID: 31253167 PMCID: PMC6599302 DOI: 10.1186/s13045-019-0753-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 06/14/2019] [Indexed: 12/26/2022] Open

Farmer T, O'Neill KL, Naslavsky N, Luo X, Caplan S. Retromer facilitates the localization of Bcl-xL to the mitochondrial outer membrane. Mol Biol Cell 2019;30:1138-1146. [PMID: 30840537 PMCID: PMC6724524 DOI: 10.1091/mbc.e19-01-0044] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open

Gravett AM, Dalgleish AG, Copier J. In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells. Sci Rep 2019;9:1544. [PMID: 30733494 PMCID: PMC6367314 DOI: 10.1038/s41598-018-38190-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 12/06/2018] [Indexed: 01/11/2023] Open

Nishihira M, Nakazato Y, Maeda S, Inoue T, Araki O, Karube Y, Chida M. Impact of tumor infiltrating lymphocytes and lymphoid follicle formation on patient survival following surgery for lung squamous cell carcinoma. Thorac Cancer 2018;10:219-225. [PMID: 30561902 PMCID: PMC6360201 DOI: 10.1111/1759-7714.12935] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/15/2018] [Accepted: 11/16/2018] [Indexed: 12/17/2022] Open

Ezzeldin N, Farouk H, Kandil DM, Darwish A, El-Bastawisy A. Impact of cell death pathway genes Fas 21377AA and FasL 2844CC polymorphisms on the risk of developing non-small cell lung cancer. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2018. [DOI: 10.1016/j.ejmhg.2017.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open

Merchant N, Nagaraju GP, Rajitha B, Lammata S, Jella KK, Buchwald ZS, Lakka SS, Ali AN. Matrix metalloproteinases: their functional role in lung cancer. Carcinogenesis 2017. [DOI: 10.1093/carcin/bgx063] [Citation(s) in RCA: 106] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open

FAIM2, as a novel diagnostic maker and a potential therapeutic target for small-cell lung cancer and atypical carcinoid. Sci Rep 2016;6:34022. [PMID: 27677402 PMCID: PMC5039724 DOI: 10.1038/srep34022] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 09/06/2016] [Indexed: 12/23/2022] Open

Sharma G, Rani I, Bhatnagar A, Agnihotri N. Apoptosis-Mediated Chemoprevention by Different Ratios of Fish Oil in Experimental Colon Carcinogenesis. Cancer Invest 2016;34:220-30. [PMID: 27191482 DOI: 10.1080/07357907.2016.1183023] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]

Yu X, Li Y, Yu Y, Lei J, Wan G, Cao F. Associations between FAS rs2234767 and FASL rs763110 polymorphisms and the risk of lung cancer: a meta-analysis of 39,736 subjects. Onco Targets Ther 2016;9:2049-56. [PMID: 27103831 PMCID: PMC4827906 DOI: 10.2147/ott.s102723] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open

Huang CC, Wu DW, Lin PL, Lee H. Paxillin promotes colorectal tumor invasion and poor patient outcomes via ERK-mediated stabilization of Bcl-2 protein by phosphorylation at Serine 87. Oncotarget 2016;6:8698-708. [PMID: 25826088 PMCID: PMC4496177 DOI: 10.18632/oncotarget.3537] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Accepted: 02/10/2015] [Indexed: 01/13/2023] Open

Azzimonti B, Zavattaro E, Provasi M, Vidali M, Conca A, Catalano E, Rimondini L, Colombo E, Valente G. Intense Foxp3+CD25+regulatory T-cell infiltration is associated with high-grade cutaneous squamous cell carcinoma and counterbalanced by CD8+/Foxp3+CD25+ratio. Br J Dermatol 2014;172:64-73. [DOI: 10.1111/bjd.13172] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2014] [Indexed: 02/01/2023]

Li L, Yao YC, Fang SH, Ma CQ, Cen Y, Xu ZM, Dai ZY, Li C, Li S, Zhang T, Hong HH, Qi WW, Zhou T, Li CY, Yang X, Gao GQ. Pigment epithelial-derived factor (PEDF)-triggered lung cancer cell apoptosis relies on p53 protein-driven Fas ligand (Fas-L) up-regulation and Fas protein cell surface translocation. J Biol Chem 2014;289:30785-30799. [PMID: 25225287 DOI: 10.1074/jbc.m114.590000] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open

Affiliation(s)

Lei Li Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China,; Department of Reproductive Medicine Center, Key Laboratory for Reproductive Medicine of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Guangzhou 510150, China
Ya-Chao Yao Laboratory Center of Guangdong No. 2 Provincial People's Hospital, Guangzhou 510317, Guangdong Province, China
Shu-Huan Fang DME Center, Clinical Pharmacology Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
Cai-Qi Ma Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Yi Cen Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Zu-Min Xu Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524000, China
Zhi-Yu Dai Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Cen Li Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Shuai Li Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Ting Zhang Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Hong-Hai Hong Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Wei-Wei Qi Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Ti Zhou Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Chao-Yang Li State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China,.
Xia Yang Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China,; China Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou 510080, China, and.
Guo-Quan Gao Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China,; Key Laboratory of Functional Molecules from Marine Microorganisms, Sun Yat-sen University, Department of Education of Guangdong Province, Guangdong 510080, China.

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Yuan HP, Liu QD, Li GQ, Cong YQ. Fas −670A/G (rs1800682) Polymorphism and Digestive Cancer Risk in Asians: A Meta-Analysis. Genet Test Mol Biomarkers 2014;18:482-8. [PMID: 24800976 DOI: 10.1089/gtmb.2014.0032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open

Zhu J, Lu L, Cheng X, Xie R, Chen Z, Li Y, Lin G, Liu J, Yang Y. Association between CD95L polymorphism and cervical cancer risk: evidence from a meta-analysis. Tumour Biol 2014;35:5137-42. [PMID: 24619598 DOI: 10.1007/s13277-014-1652-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Accepted: 01/12/2014] [Indexed: 01/17/2023] Open

Wang X, Xing GH, Fan CC. Association between the FAS rs2234767G/A polymorphism and cancer risk: a systematic review and meta-analysis. DNA Cell Biol 2014;33:320-7. [PMID: 24568648 DOI: 10.1089/dna.2013.2273] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open

FasL gene -844T/C mutation of esophageal cancer in South China and its clinical significance. Sci Rep 2014;4:3866. [PMID: 24473454 PMCID: PMC5379236 DOI: 10.1038/srep03866] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 01/07/2014] [Indexed: 01/22/2023] Open

FAS−1377 A/G polymorphism in breast cancer: a meta-analysis. Tumour Biol 2013;35:2575-81. [DOI: 10.1007/s13277-013-1339-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 10/16/2013] [Indexed: 01/04/2023] Open

Zhong-Xing Z, Yuan-Yuan M, Hai Zhen M, Jian-Gang Z, Li-Feng Z. FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis of 17,858 cases and 24,311 controls. PLoS One 2013;8:e73700. [PMID: 24014103 PMCID: PMC3754923 DOI: 10.1371/journal.pone.0073700] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Accepted: 07/19/2013] [Indexed: 12/20/2022] Open

Abstract

BACKGROUND AND OBJECTIVES

Disruption of apoptosis has been implicated in carcinogenesis. Specifically, various single-nucleotide polymorphisms (SNPs) in apoptotic genes, such as FAS-1377 G/A SNP, have been associated with cancer risk. FAS-1377 G/A SNP has been shown to alter FAS gene promoter transcriptional activity. Down-regulation of FAS and cell death resistance is key to many cancers, but an association between FAS-1377 G/A SNP and cancer risk is uncertain. Therefore, we conducted a meta-analysis of the current literature to clarify this relationship.

METHODOLOGY/PRINCIPAL FINDINGS

From PubMed and Chinese language (CNKI and WanFang) databases, we located articles published up to March 5, 2013, obtaining 44 case-control studies from 41 different articles containing 17,858 cases and 24,311 controls based on search criteria for cancer susceptibility related to the FAS gene -1377 G/A SNP. Odds ratios (ORs) and 95% confidence intervals (CI) revealed association strengths. Data show that the -1377 G allele was protective against cancer risk. Similar associations were detected in "source of control," ethnicity and cancer type subgroups. Lower cancer risk was found in both smokers with a GG+GA genotype and in non-smokers with the GG+GA genotype, when compared to smokers and nonsmokers with the AA genotype. Males carrying the -1377G allele (GG+GA) had lower cancer incidence than those with the AA genotype. Individuals who carried both FAS-1377(GG+GA)/FASL-844(TT+TC) genotypes appeared to have lower risk of cancer than those who carried both FAS-1377 AA/FASL-844 CC genotypes.

CONCLUSIONS/SIGNIFICANCE

The FAS-1377 G/A SNP may decrease cancer risk. Studies with larger samples to study gene-environment interactions are warranted to understand the role of FAS gene polymorphisms, especially -1377 G/A SNP, in cancer risk.

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Functional Investigation of Fas Ligand Expressions in Human Non-Small Cell Lung Cancer Cells and Its Clinical Implications. Ann Thorac Surg 2013;95:412-8. [DOI: 10.1016/j.athoracsur.2012.08.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Revised: 07/31/2012] [Accepted: 08/02/2012] [Indexed: 01/06/2023]

Chen CJ, Sung WW, Su TC, Chen MK, Wu PR, Yeh KT, Ko JL, Lee H. High expression of interleukin 10 might predict poor prognosis in early stage oral squamous cell carcinoma patients. Clin Chim Acta 2013;415:25-30. [PMID: 22981868 DOI: 10.1016/j.cca.2012.09.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2012] [Revised: 08/30/2012] [Accepted: 09/06/2012] [Indexed: 11/20/2022]

Tian J, Pan F, Li J, Ma Y, Cen H, Pan HF, Pan YY, Ye DQ. Association between the FAS/FASL polymorphisms and gastric cancer risk: a meta-analysis. Asian Pac J Cancer Prev 2012;13:945-51. [PMID: 22631677 DOI: 10.7314/apjcp.2012.13.3.945] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open

Hammam O, Mahmoud O, Zahran M, Aly S, Hosny K, Helmy A, Anas A. The role of fas/fas ligand system in the pathogenesis of liver cirrhosis and hepatocellular carcinoma. HEPATITIS MONTHLY 2012;12:e6132. [PMID: 23300494 PMCID: PMC3539063 DOI: 10.5812/hepatmon.6132] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Revised: 08/01/2012] [Accepted: 08/15/2012] [Indexed: 12/11/2022]

Abstract

BACKGROUND

The Fas receptor/ligand system including soluble forms is the most important apoptotic initiator in the liver. Dysregulation of this pathway may contribute to abnormal cell proliferation and cell death and is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells.

OBJECTIVES

To analyze the role of Fas system Fas/ Fas ligand (Fas/ FasL) in the multi-step process of hepatic fibrosis/carcinogenesis, and to use of the serum markers as possible candidate biomarkers for early detection of hepatocellular carcinoma (HCC).

PATIENTS AND METHODS

NINETY PATIENTS WERE ENROLLED: 30 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis, and 30 cases of HCC and hepatitis V virus (HCV) infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, were served as normal controls. Serum soluble Fas (sFas) levels were measured using ELISA technique; Fas and FasL proteins were detected in hepatic tissue by indirect Immuno-histochemical technique (IHC); electron microscopic (EM) and immune electron microscopic examinations were performed for detection of Fas expression on lymphocytes.

RESULTS

Hepatic expression of both Fas and FasL as well as expression of Fas on separated lymphocytes were significantly increased in the diseased groups (P < 0. 01) compared to the control specimens. The highest expression was noticed in CHC specimens, particularly with the necro-inflammatory activity and advancement of the fibrosis. The sFas in cirrhotic patients and HCC were significantly higher than that in normal controls and CHC without cirrhosis group (P < 0.01).

CONCLUSIONS

Apoptosis and the Fas system were significantly involved in the process of converting liver cirrhosis into hepatocellular carcinoma. Down-regulation of Fas expression, up regulation of FasL expression in hepatocytes, and elevation of serum sFas levels were important in tumor evasion from immune surveillance, and in hepatic carcinogenesis.

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Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY) 2012;4:330-49. [PMID: 22683550 PMCID: PMC3384434 DOI: 10.18632/aging.100459] [Citation(s) in RCA: 386] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Wu DW, Tsai LH, Chen PM, Lee MC, Wang L, Chen CY, Cheng YW, Lee H. Loss of TIMP-3 promotes tumor invasion via elevated IL-6 production and predicts poor survival and relapse in HPV-infected non-small cell lung cancer. THE AMERICAN JOURNAL OF PATHOLOGY 2012;181:1796-806. [PMID: 22982189 DOI: 10.1016/j.ajpath.2012.07.032] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Revised: 06/19/2012] [Accepted: 07/20/2012] [Indexed: 12/21/2022]

Kayser G, Schulte-Uentrop L, Sienel W, Werner M, Fisch P, Passlick B, Zur Hausen A, Stremmel C. Stromal CD4/CD25 positive T-cells are a strong and independent prognostic factor in non-small cell lung cancer patients, especially with adenocarcinomas. Lung Cancer 2012;76:445-51. [PMID: 22300751 DOI: 10.1016/j.lungcan.2012.01.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Revised: 11/16/2011] [Accepted: 01/07/2012] [Indexed: 12/20/2022]

Sung WW, Wang YC, Cheng YW, Lee MC, Yeh KT, Wang L, Wang J, Chen CY, Lee H. A polymorphic -844T/C in FasL promoter predicts survival and relapse in non-small cell lung cancer. Clin Cancer Res 2011;17:5991-5999. [PMID: 21807637 DOI: 10.1158/1078-0432.ccr-11-0227] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]

Immunotherapy for lung cancers. J Biomed Biotechnol 2011;2011:250860. [PMID: 21318107 PMCID: PMC3035001 DOI: 10.1155/2011/250860] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2010] [Revised: 11/15/2010] [Accepted: 12/23/2010] [Indexed: 11/21/2022] Open

Cao Y, Miao XP, Huang MY, Deng L, Lin DX, Zeng YX, Shao JY. Polymorphisms of death pathway genes FAS and FASL and risk of nasopharyngeal carcinoma. Mol Carcinog 2010;49:944-50. [PMID: 20842669 DOI: 10.1002/mc.20676] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]

Shunmei E, Zhao Y, Huang Y, Lai K, Chen C, Zeng J, Zou J. Heat shock factor 1 is a transcription factor of Fas gene. Mol Cells 2010;29:527-31. [PMID: 20396959 DOI: 10.1007/s10059-010-0065-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2009] [Revised: 01/28/2010] [Accepted: 01/29/2010] [Indexed: 01/17/2023] Open

[Anti-apoptotic mechanisms in small-cell lung carcinoma]. Ann Pathol 2010;30:17-24. [PMID: 20223350 DOI: 10.1016/j.annpat.2009.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2009] [Indexed: 01/23/2023]

Zhu Q, Wang T, Ren J, Hu K, Liu W, Wu G. FAS-670A/G polymorphism: A biomarker for the metastasis of nasopharyngeal carcinoma in a Chinese population. Clin Chim Acta 2010;411:179-83. [DOI: 10.1016/j.cca.2009.10.024] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2009] [Revised: 10/25/2009] [Accepted: 10/29/2009] [Indexed: 01/10/2023]

Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer. Gen Thorac Cardiovasc Surg 2009;57:449-57. [DOI: 10.1007/s11748-008-0433-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2008] [Indexed: 01/25/2023]

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Park JY, Lee WK, Jung DK, Choi JE, Park TI, Lee EB, Cho S, Park JY, Cha SI, Kim CH, Kam S, Jung TH, Jheon S. Polymorphisms in theFASandFASLGenes and Survival of Early Stage Non–small Cell Lung Cancer. Clin Cancer Res 2009;15:1794-800. [DOI: 10.1158/1078-0432.ccr-08-1770] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]

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Prado-Garcia H, Aguilar-Cazares D, Meneses-Flores M, Morales-Fuentes J, Lopez-Gonzalez JS. Lung carcinomas do not induce T-cell apoptosis via the Fas/Fas ligand pathway but down-regulate CD3 epsilon expression. Cancer Immunol Immunother 2008;57:325-36. [PMID: 17668204 PMCID: PMC11030893 DOI: 10.1007/s00262-007-0372-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2007] [Accepted: 07/11/2007] [Indexed: 10/23/2022]

Abstract

BACKGROUND

Non-small cell lung carcinoma (NSCLC) patients have impaired cellular immune responses. It has been hypothesized that tumor cells expressing Fas Ligand (FasL) induce in T lymphocytes: (a) apoptosis (tumor counterattack) and (b) down-regulation of CD3zeta expression. However, the hypothesis of tumor counterattack is still controversial.

METHODS

We analyzed FasL expression on NSCLC cell lines and on tumor cells from lung adenocarcinoma patients by flow cytometry and immunocytochemistry. FasL mRNA expression was detected in NSCLC cell lines using RT-PCR, and functional FasL was evaluated on Fas-expressing Jurkat T-cells by annexin-V-FITC staining and by SubG(1) peak detection. Also, the proapoptotic effect of microvesicles released from NSCLC cell lines in Jurkat T-cells was studied. Alterations in the expression levels of CD3zeta, CD3epsilon, and CD28 [measured as mean fluorescence intensity (MFI)] were determined in Jurkat T-cells after co-culture with NSCLC cell lines or tumor-derived microvesicles. Furthermore, the expression levels of CD3zeta and CD3epsilon in CD4+T and CD8+T lymphocytes from lung adenocarcinoma patients was studied.

RESULTS

Our results indicate that NSCLC cells neither FasL expressed nor induced apoptosis in Jurkat T-cells. Tumor-derived microvesicles did not induce apoptosis in Jurkat T-cells. In contrast, NSCLC cell lines down-regulated CD3epsilon but not CD3zeta chain expression in Jurkat T-cells; this effect was induced by soluble factors but not by microvesicles. In lung adenocarcinoma patients, significant decreases of MFI values for CD3epsilon, but not CD3zeta, were found in CD4+T and CD8+T cells from pleural effusion compared to peripheral blood and in peripheral blood of patients compared to healthy donors.

CONCLUSIONS

Our data do not support the tumor counterattack hypothesis for NSCLC. Nonetheless, down-regulation of CD3epsilon in T-cells induced by NSCLC cells might lead to T-cell dysfunction.

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