Role and prognostic significance of tumor necrosis factor‐related apoptosis‐inducing ligand death receptor DR5 in nonsmall‐cell lung cancer and precursor lesions

Cooper, Wendy A.; Kohonen‐Corish, Maija; Zhuang, Liqing; McCaughan, Brian C.; Kennedy, Catherine; Screaton, Gavin; Sutherland, Robert L.; Lee, Cheok Soon

doi:10.1002/cncr.23528

Cited by 33 publications

(29 citation statements)

References 42 publications

(54 reference statements)

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“…Indeed McCarthy and Ganten reported a higher expression rate of TRAIL-R2 associated to a shorter survival in breast cancer [30,31]. Cooper et al, described the same results in the non-small' cell lung cancer [32]. These discrepancies underline the complexity of interactions between TRAIL receptors and the intracellular apoptotic machinery.…”

Section: Discussionmentioning

confidence: 91%

Tissue Prognostic Factors in Melanoma: Expression of B7 Family Members B7-H3 and B7-H4 and Death Receptors TRAIL-R1 and TRAILR2

Aubert-Wastiaux¹

2012

TOIJ

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High resistance rate of melanoma to chemotherapy results in the development of other therapeutic strategies such as immunotherapy. Discrepancies observed in clinical responses to immunotherapy suggest the presence of immune polymorphisms and tumor escape mechanisms.The objective of this study was to investigate the expression of B7-H3 and B7-H4 which are major stakeholders in immune regulation, and of the death receptors TRAIL-R1 and TRAIL-R2 which play an important role in controlling tumor cell proliferation and apoptosis. The correlation between the expression levels of these proteins and the clinical outcome has also been assessed.The expression level of the proteins was analyzed on 32 invaded LN samples and on 11 matching tumor cell lines. Immunohistochemical staining and double fluorescent immunostaining on lymph node (LN) frozen sections were performed, as well as flow cytometry on tumor cell lines.The 4 proteins were expressed in all LN biopsies within a range from 40.6% for TRAIL-R1 to 87.5% for TRAIL-R2. These 4 proteins were rarely expressed by the tumor cell lines except for TRAIL-R2 which was detected in 10 of the 11 cell lines. The expression of these proteins by tumor cell lines is not correlated with in vivo expression found in immunohistochemistry (IHC). It raises the question of the role of the tissue environment in the expression of the proteins. The expression levels of B7-H4, TRAIL-R1, and TRAIL-R2 using IHC were correlated with overall survival. In vivo, high expression levels of B7-H4, TRAIL-R1 or TRAIL-R2 appear as poor prognostic factors.

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Section: Discussionmentioning

confidence: 91%

Tissue Prognostic Factors in Melanoma: Expression of B7 Family Members B7-H3 and B7-H4 and Death Receptors TRAIL-R1 and TRAILR2

Aubert-Wastiaux¹

2012

TOIJ

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“…Apart from cell cycle arrest, apoptosis is another cause of growth inhibition (26). Apoptosis, or programmed cell death, is an essential mechanism through which many types of chemotherapeutic agents inhibit tumor growth (27). Mitochondria-initiated responses are thought to be the major pathway for apoptosis, and, therefore, targeting the mitochondria is a novel strategy for cancer therapy (10).…”

Section: Discussionmentioning

confidence: 99%

CDK5RAP1 deficiency induces cell cycle arrest and apoptosis in human breast cancer cell line by the ROS/JNK signaling pathway

Wang

et al. 2015

Oncology Reports

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Abstract. Cyclin-dependent kinase 5 regulatory subunit associated protein 1 (CDK5RAP1) is an enzyme which post-synthetically converts the RNA modification N6-isopentenyladenosine (i 6 A) into 2-methylthio-N6-isopentenyladenosine (ms 2 i 6 A). However, the interaction between CDK5RAP1 deficiency and cell apoptosis has not been studied. Breast cancer has long been a leading cause of mortality in the world. Therefore, in the present study, CDK5RAP1 deficiency in a human breast cancer cell line was investigated. CDK5RAP1 small interfering RNA (siRNA) and negative control siRNA were transfected into MCF-7 cells, and the cells were further incubated for 48 h. CDK5RAP1 deficiency suppressed tumor growth in MCF-7 cells and arrested the cells at G2/M phase. CDK5RAP1 deficiency also induced cell apoptosis and reactive oxygen species (ROS) generation. Furthermore, western blot analysis showed that the expression of phospho-c-Jun N-terminal kinase (p-JNK), p53, caspase-9 and caspase-3 were upregulated in CDK5RAP1-deficient MCF-7 cells. Pretreatment with N-acetyl-cysteine (NAC), the inhibitor of ROS, or with SP600125, the inhibitor of JNK, prevented the apoptosis and the high expression of p-JNK, p53, caspase-9 and caspase-3 in CDK5RAP1-deficient MCF-7 cells. Taken together, these data indicated that CDK5RAP1 deficiency induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells by the ROS/JNK signaling pathway. Our findings indicated a novel therapeutic strategy for cancer. IntroductionCyclin-dependent kinase 5 regulatory subunit associated protein 1 (CDK5RAP1) is a radical S-adenosyl methionine (SAM) enzyme (1) with homology to the bacterial MiaB protein (2), which post-synthetically converts the RNA modification N6-isopentenyladenosine (i 6 A) into 2-methylthio-N6-isopentenyladenosine (ms 2 i 6 A) at A37 (3), as shown in Fig. 1A. It was discovered to inhibit the active CDK5 kinase and function in codon suppression (4) and stabilization of the codon/anticodon interaction (5). CDK5 aberrant regulation can lead to a number of diseases (6). The biochemical link established by CDK5RAP1 between the enzymatic modification of transfer RNA (tRNA) tanticodon loops and CDK5 kinase activity is highly unusual, particularly since the modified base ms 2 i 6 A is known to exist in tRNA of prokaryotic origin (7), particularly in mitochondrial tRNA of mammals (8).Breast cancer has long been a leading cause of mortality in women worldwide (9). Due to the limited efficacy of traditional therapy, it is necessary to exploit a new treatment strategy for breast cancer. Mitochondria-initiated responses are thought to be the major pathway for apoptosis, and, therefore, targeting the mitochondria is a novel strategy for cancer therapy (10). Hence, in the present study, we sought to determine if the mistranslation of ms 2 i 6 A in mitochondrial tRNA caused by CDK5RAP1 deficiency affects the human breast cancer cell line, MCF-7 cells.Cell cycle arrest is an important cause of growth inhibition. Many anticancer agents reduce malignant g...

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“…TRAIL mediates apoptosis through two death receptors, TRAIL-receptor 1 (TRAIL-R1) and TRAIL-receptor 2 (TRAIL-R2) expressed on cell surface. NSCLC patients have high tumor concentrations of TRAIL-R1 (in 67% to 99% of tumor biopsies) [175,176]. TRAIL-R2 was detected in 82% of NSCLC tumor biopsies [176].…”

Section: Trail Agonist Antibodiesmentioning

confidence: 99%

“…NSCLC patients have high tumor concentrations of TRAIL-R1 (in 67% to 99% of tumor biopsies) [175,176]. TRAIL-R2 was detected in 82% of NSCLC tumor biopsies [176]. Several antibodies which are TRAIL agonist have been developed [177].…”

Section: Trail Agonist Antibodiesmentioning

confidence: 99%

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Guilleminault¹,

Lemarié²,

Heuzé-Vourc’h³

2012

JCT

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Lung cancer is the leading cause of cancer-related deaths in industrialized countries and non small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cisplatin doublet based chemotherapy, which is the recommended regimen in first line therapy in advanced or metastatic NSCLC, improves survival but in low proportion. Monoclonal antibodies (mAbs) are a novel promising therapeutic class used with great results in inflammatory diseases such as rheumatoid arthritis. Antibodies are natural proteins with modular structure, specific pharmacodynamics and pharmacokinetics and possibly produced against any antigens, thus giving them several advantages over small drug therapeutics. In solid tumors, therapeutic mAbs improved progression free survival (PFS) and overall survival (OS) of patients with breast and colon cancers and had considerably changed the treatment in clinical practice. In NSCLC, bevacizumab, an anti-VEGF mAb, and cetuximab, an anti-EGFR mAb, are the most studied antibodies. Bevacizumab acts on angiognenesis and improved PFS of non squamous NSCLC but in low proportion as shown in two large phase III trials. It was approved by European Medicines Agency (EMEA) and Food and Drug administration (FDA) as a first line therapy in combination with cisplatin doublet chemotherapy. Cetuximab slightly enhanced OS but did not improve PFS in two large phase III trials. These results added to high adverse effect lead to cetuximab refusal by EMEA and FDA in NSCLC. At first glance, the results of mAbs in NSCLC are somewhat disappointing, in contrast to the benefits obtained with mAb treatments in other solid tumors. However, many other mAbs directed against novel targets, such as IGF1-R or CTLA-4, and new mAbs targeting VEGFR and EGFR pathways with different pharmacodymamical and pharmacokinetic properties are under evaluation and may change our vision of taking care of patients with NSCLC. In conclusion, it seems that mAbs therapy in NSCLC clearly marks the start of a new era in NSCLC treatment, with promises in improving patient survival and quality of life.

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Role and prognostic significance of tumor necrosis factor‐related apoptosis‐inducing ligand death receptor DR5 in nonsmall‐cell lung cancer and precursor lesions

Cited by 33 publications

References 42 publications

Tissue Prognostic Factors in Melanoma: Expression of B7 Family Members B7-H3 and B7-H4 and Death Receptors TRAIL-R1 and TRAILR2

Tissue Prognostic Factors in Melanoma: Expression of B7 Family Members B7-H3 and B7-H4 and Death Receptors TRAIL-R1 and TRAILR2

CDK5RAP1 deficiency induces cell cycle arrest and apoptosis in human breast cancer cell line by the ROS/JNK signaling pathway

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

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