ABSTRACT
AIMS: Preferential expression of receptors for TNF-family related apoptosis inducing ligand (TRAIL), DR4 and DR5 makes TRAIL an attractive anti-cancer therapeutic. However, the efficacy of targeting death receptors has not been extensively studied in nasopharyngeal cancer (NPC). Here we investigated TRAIL sensitivity and its underlying mechanism in NPC cell lines, and assessed the potential of TRAIL as a therapeutic option against NPC. RESULTS: Using two established NPC cell lines, we report the expression of DR4 and DR5, which respond to TRAIL ligation by triggering efficient Type II apoptosis. Mechanistically, early activation of caspase-3 and its membrane recruitment is identified in NPC cell lines, which is associated with, hitherto unreported, interaction with transmembrane and tetratricopeptide repeat containing 2 (TMTC2) in the lipid raft domains. TMTC2 expression is induced upon exposure to TRAIL and involves intracellular increase in peroxynitrite (ONOO-) production. While ONOO- increase is downstream of caspase-8 activation, it is involved in the upregulation of TMTC2, gene knockdown of which abrogated TRAIL-induced apoptotic execution. Bioinformatics analyses also provide evidence for a strong correlation between TMTC2 and DR4 or caspase-3 as well as a significantly better disease-free survival in patients with high TMTC2 expression. INNOVATION AND CONCLUSION: Collectively, redox-dependent execution of NPC cells upon ligation of TRAIL receptors reintroduces the possible therapeutic use of TRAIL in NPC as well as underscores the potential of using TMTC2 as a biomarker of TRAIL sensitivity.
ABSTRACT
Chyle leaks after a neck dissection usually manifest within the immediate postoperative period. However, masked chyle leaks may present as a chyloma months later. A 54-year-old male patient with squamous cell carcinoma of the tongue underwent bilateral neck dissection, subtotal glossectomy, anterolateral thigh flap reconstruction and postoperative radiotherapy. Intraoperatively, chyle leak was encountered in level IV of the left neck. We managed it by ligation of the thoracic duct, application of Tisseel™ sealant (Baxter Inc., Illinois, USA) and one week of prophylactic fat-free feeds. Six months later, an asymptomatic chyloma of the left neck was identified on surveillance MRI. Five weeks after the diagnosis, streptococcal infection developed within the chyloma. However, initiation of fat-free diet, serial aspiration, pressure dressing and antibiotic therapy allowed the chyloma to resolve within two weeks. Further surveillance MRI over three years showed no recurrence of the chyloma. Low-volume chyle leaks may manifest as an occult chyloma. Prophylactic measures cannot replace meticulous ligation of chylous channels in left level IV neck dissection.
ABSTRACT
INTRODUCTION: This study aims to evaluate the results of foot screening performed in a study population of 2137 diabetics (3926 feet) screened from 2006 to 2008 by the National University Hospital (NUH) multi-disciplinary team for diabetic foot problems. MATERIALS AND METHODS: A standardised protocol was designed. Foot screening consisted of detailed history taking and clinical examination including assessment for sensory neuropathy by Semmes Weinstein monofilament (SWMF) and neurothesiometer and assessment of vasculopathy by ankle-brachial index (ABI) and total body irradiation (TBI). The foot screening was performed by a trained staff nurse. All patients were classified according to King's College Classification. RESULTS: Majority of the patients were in the fifth (27.9%) and sixth (30.0%) decades of life. Two thousand sixty-four had type II diabetes, and only 73 had type I diabetes. Neuropathy was found in 1307 (33.3%) feet based on 5.07 SWMF. Vasculopathy was recorded in 510 (13.0%) and 546 (13.9%) feet based on ABI <0.8 and TBI <0.7. According to King's Classification, 1069 (50.0%) were Stage 1: Normal and 615 (28.8%) were Stage 2: At-Risk. CONCLUSION: Foot screening should be performed as early as possible to detect "At-Risk" feet and prevent the development of diabetic foot complications, thereby further reducing the risk of major amputations.
