Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma

Younes, Mamoun; Georgakis, Georgios V.; Rahmani, Mahdis; Beer, David G.; Younes, Anas

doi:10.1016/j.ejca.2005.11.013

Cited by 23 publications

(10 citation statements)

References 28 publications

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“…It should be noted that although cytoplasmic and nuclear staining of all the receptors was frequently observed during our examination of specimens for DR4, DR5, DcR1 and DcR2, this was not subjected to further analysis. As with other similar studies on breast and esophageal cancers [11, 12], membrane staining of both or one death receptor for TRAIL was found only in 39/159 EAC cases (24.6 %). Interestingly, in contrast to the EAC samples, strong membrane expression of DR4 and/or DR5 was present in 14/20 NE (70.0 %) and 11/18 AEH (61.1 %) cases.…”

Section: Discussionsupporting

confidence: 88%

“…TRAIL receptors show both cell membrane and cytoplasmic staining [9, 11, 12], and in some cases, the receptors can be also expressed in the nucleus [12]. Nowadays it is known that TRAIL and its receptors are present in many normal human tissues, e.g., in peripheral leukocytes, hepatocytes, neurons, renal tubuli contorti, heart myocytes, colonic luminal epithelium and crypt cells, bronchial epithelium and alveolar septa, heart myocytes, germ and Leydig cells [8–10].…”

Section: Discussionmentioning

confidence: 99%

“…To characterize TRAIL receptors in cancers, cytoplasmic staining is usually analyzed rather than membrane or nuclear staining [9, 12]. The cytoplasmic expression of DR4 and DR5 was found to be strong in primary and metastatic brain tumors, leukemias, malignant melanomas and cancers of the breast, lung, head and neck, esophagus, colorectum, pancreas, renal, urinary bladder, uterine cervix and ovaries [8, 9, 11–13, 25, 26]. Similarly, the cytoplasmic expression of DcR1 and DcR2 was reported, e.g., in primary and metastatic brain tumors [8] and in prostate cancer [27].…”

Section: Discussionmentioning

confidence: 99%

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Membrane expression of TRAIL receptors DR4, DR5, DcR1 and DcR2 in the normal endometrium, atypical endometrial hyperplasia and endometrioid adenocarcinoma: a tissue microarray study

Gottwald

Piekarski

Kubiak

et al. 2013

Arch Gynecol Obstet

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PurposeTo evaluate the membrane expression of DR4, DR5, DcR1 and DcR2 in the normal endometrium (NE), atypical endometrial hyperplasia (AEH) and endometrioid adenocarcinoma (EAC).MethodsThe study comprised 197 patients: 20 NE, 18 AEH and 159 EAC. Tissue microarrays were constructed. Membrane expression of DR4, DR5, DcR1 and DcR2 was examined and presented as total score (TS).ResultsIn EAC, the membrane expression of DR4, DR5 and DcR2 was less common compared to NE (p < 0.001; p < 0.001; p = 0.018) and AEH (p < 0.001; p < 0.001; p = 0.004). In EAC the membrane expression of DcR1 did not differ when compared to NE (p = 0.055) and AEH (p = 0.173). A strong correlation was found between the type of endometrial tissue (NE/AEH/EAC) and the TS of DR4 (p < 0.001), DR5 (p < 0.001), DcR1 (p = 0.033) and DcR2 (p < 0.001). In EAC, the TS of DR4, DR5, DcR1 and DcR2 was not related to grading and staging. In EAC, the membrane expression of DR5, but not DR4, DcR1 and DcR2, was related to better disease-free survival (DFS). The overall survival (OS) was not related to membrane TRAIL receptors expression.ConclusionsThe membrane expression of the receptors for TRAIL DR4, DR5, DcR1 and DcR2 is greater in NE than EAC. The level of membrane staining of the receptors in EAC is not dependent on grading and staging. In EAC patients, membrane expression of DR4, DR5, DcR1 and DcR2 are not independent predictors of survival.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Membrane expression of TRAIL receptors DR4, DR5, DcR1 and DcR2 in the normal endometrium, atypical endometrial hyperplasia and endometrioid adenocarcinoma: a tissue microarray study

Gottwald

Piekarski

Kubiak

et al. 2013

Arch Gynecol Obstet

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“…The extrinsic pathway of apoptosis is activated by tumor necrosis factor (TNF) family ligands that engage death receptors, resulting in activation of caspases and apoptosis 50 . The TNF apoptosis‐inducing ligand (TRAIL) receptors are one member of the family of death receptors found expressed in esophageal tumors 51 . Mapatumumab and lexatumumab are agonistic human MoAb that specifically bind to TRAIL receptor‐1 and ‐2, thus directly inducing apoptosis.…”

Section: Targeting Apoptosismentioning

confidence: 99%

Novel targeted therapies for advanced esophageal cancer

Lin¹,

Papadopoulos

2007

Diseases of the Esophagus

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Esophageal cancer is highly aggressive and is the sixth leading cause of cancer death worldwide. Recent advances in multimodality chemoradiotherapy and surgery has improved survival in patients with loco-regional disease, but most patients with advanced stage esophageal cancer have a poor prognosis. Elucidation of the processes involved in esophageal carcinogenesis has identified a number of promising novel targets for therapy. This review focuses on the current status of targeted therapies with potential application to the treatment of advanced esophageal and gastroesophageal junction cancer. The future challenge is to confirm the efficacy of these targeted agents in appropriately selected esophageal cancer patients, and successfully integrate these agents into effective therapies for all stages and subtypes of disease.

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“…Second, they also call into question the efficacy of the death receptor agonists as an effective therapeutic modality in tumors where c-FLIP is overexpressed, as these cells have the potential to diverge from an apoptotic signaling onto other proliferative pathways. Currently, there are several humanized anti-TRAIL-R1 and anti-TRAIL-R2 antibodies undergoing phase I/II clinical trials (31,32) singly and in combination with other chemotherapeutic agents. For example, the novel anticancer molecule HGS-ETR1 that specifically binds to TRAIL-R1 has been shown to be effective both in vitro and in vivo in a wide variety of human tumor xenografts (31).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%