Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of XhoI restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type.
Spheroids have been shown to recapitulate the tumour in vivo with properties
such as the tumour microenvironment, concentration gradients, and tumour phenotype. As
such, it can serve as a platform for determining the growth and invasion behaviour pattern
of the cancer cells as well as be utilised for drug sensitivity assays; capable of exhibiting
results that are closer to what is observed in vivo compared to two-dimensional (2D) cell
culture assays. This study focused on establishing a three-dimensional (3D) cell culture
model using the Nasopharyngeal Carcinoma (NPC) cell line, HK1 and analysing its growth
and invasion phenotypes. The spheroids will also serve as a model to elucidate their
sensitivity to the chemotherapeutic drug, Flavopiridol. The liquid overlay method was
employed to generate the spheroids which was embedded in bovine collagen I matrix for
growth and invasion phenotypes observation. The HK1 cells formed compact spheroids
within 72 hours. Our observation from the 3 days experiments revealed that the spheroids
gradually grew and invaded into the collagen matrix, showing that the HK1 spheroids are
capable of growth and invasion. Progressing from these experiments, the HK1 spheroids
were employed to perform a drug sensitivity assay using the chemotherapeutic drug,
Flavopiridol. The drug had a dose-dependent inhibition on spheroid growth and invasion.
The BCL-2 anti-apoptotic proteins are over-expressed in many cancers and hence are attractive therapeutic targets. In this study, we tested the sensitivity of two Nasopharyngeal Carcinoma (NPC) cell lines HK1 and C666-1 to Maritoclax, which is reported to repress anti-apoptotic protein MCL-1 and BH3 mimetic ABT-263, which selectively inhibits anti-apoptotic proteins BCL-2, BCL-XL and BCL-w. We investigated the sensitisation of the NPC cell lines to these drugs using the SYBR Green I assay and 3D NPC spheroids. We report that Maritoclax repressed anti-apoptotic proteins MCL-1, BCL-2, and BCL-XL in a dose- and time-dependent manner and displayed a single agent activity in inhibiting cell proliferation of the NPC cell lines. Moreover, combination of Maritoclax and ABT-263 exhibited synergistic antiproliferative effect in the HK1 cells. Similar results were obtained in the 3D spheroids generated from the HK1 cells. More notably, 3D HK1 spheroids either treated with single agent Maritoclax or combination with ABT-263, over 10 days, did not develop resistance to the treatment rapidly. Collectively, the findings illustrate that Maritoclax as a single agent or combination with BH3 mimetics could be potentially useful as treatment strategies for the management of NPC.
Increasing evidence of the association between ribosomal protein (RP) genes with nasopharyngeal carcinoma (NPC) have been derived from findings of their differential expression patterns in NPC cell lines. Nevertheless, expression data from a comprehensive list of RP gene family members is still lacking. This paper reports the assessment of two RP genes, eL13 and eL14, with regards to their expression patterns in several NPC cell lines (TW04, TW01, HK1, HONE1 and SUNE-1) relative to a non-malignant control (NP69). A conventional Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay was employed. Analysis of eL13 has never been explored before this, whereas investigation of eL14 represents an extended study. We found a general over-expression trend of eL14 in 40% (2 of 5; TW01 and HONE-1) of the NPC cell lines studied, with higher upregulated level in only one (TW01) of them. However, this pattern of expression level is not statistically significant. Expression of eL13 was not detected in any of the cell lines used. The inconsistency of these expression patterns demonstrates an elusive nature of RP activities in the malignancy of the nasopharynx.
The proteomics approach was adopted to study the simultaneous expression of serum proteins in patients with nasopharyngeal carcinoma (NPC). We have subjected unfractionated whole sera of ten newly diagnosed Malaysian Chinese patients with WHO type III NPC to two-dimensional gel electrophoresis (2-DE) and image analysis. The results obtained were then compared to that generated from sera of ten normal healthy controls of the same ethnic group and range of age. Our data demonstrated that the serum high abundance 2-DE protein profiles of NPC patients were generally similar to that of the controls, with exception of the ceruloplasmin (CPL) spots (identified by mass spectrometric analysis and MASCOT database search), which showed higher expression. The enhanced expression of CPL in the patients' sera was confirmed by competitive ELISA. Immunohistochemical analysis of nasopharyngeal lesions of NPC patients demonstrated moderate to strong positive CPL staining in the cytoplasm of cells at the regions of malignancy but only weak cytoplasmic staining at normal epithelial lining areas. When follow-up 2-DE and ELISA studies were performed on five of the NPC patients who responded positively to six months treatment, the difference in CPL expression was no longer significant.
Serum tumor necrosis factor alpha (TNF) concentration was assayed in 105 patients with nasopharyngeal carcinoma using a sensitive ELISA technique with detection level of 10 pg/ml. The TNF levels were detectable in 45 of 63 (71.4%) patients newly diagnosed for the malignancy and 29 of 42 (69%) patients in remission following treatment with radiotherapy. In 25 normal controls the TNF were less than 10 pg/ml. While TNF may be present in the majority of the patients with the malignant disease, the TNF concentration appeared to have no clinical significance in diagnosis or prognosis of the patients.
The antibody titres to P. falciparum and Epstein-Barr Virus-associated antigens were assayed in 22 patients with NPC and 43 controls. All, but one patient had antimalarial titres; 14 had titres greater than 80 and 4 patients greater than 640. Compared to controls the mean anti-malarial titre for most age groups were higher in the patients. Those patients with high anti-malarial titres also had high IgA anti-VCA titre, an antibody which has been demonstrated to be diagnostic for NPC. The peak anti-VCA (IgG) and anti-EA (IgG) antibody titres were associated with anti-falciparum titres of 320-640 and 80-160, respectively. The results are discussed in relation to the possible association between malarial infection and etiology of NPC.
BACKGROUND: The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.
METHODS: EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.
RESULTS: Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.
CONCLUSIONS: Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.
Nasopharnygeal carcinoma is known to be the commonest tumour of the nasopharynx. However, the incidence of nasopharngeal carcinosarcoma is extremely rare. Carcinosarcoma has been reported to be aggressive in nature and therefore early diagnosis and prompt treatment is important. We report a young lady who was diagnosed with nasopharyngeal carcinosarcoma in our centre. She presented with only 2 weeks history of nose block and was noted to have a mass occupying the nasopharynx with neck metastasis. She underwent panendoscope and biopsy with radical radiotherapy.
Adult-onset dermatomyositis has been found to be associated with underlying malignancies in up to 40% of patients. The aims of this study were to determine the demographic profile, the underlying cancer and outcome in patients with dermatomyositis. This was a retrospective review of 38 patients with dermatomyositis seen over a 12-year period in the Department of Dermatology, Kuala Lumpur Hospital. Of these, 18 (47.4%) had an associated underlying malignancy. The male to female ratio was 2:1. Ten patients (55.6%) were Chinese. The youngest patient encountered was 32 years old. Nasopharyngeal carcinoma (61.1%) was the most common malignancy in our study population. Tumour markers were not useful as the initial screening for malignancies. Thorough screening for malignancy is imperative in adult dermatomyositis especially those above 40 years old.
Shifting the paradigm of treatment of a locally recurrent nasopharyngeal carcinoma (NPC) from the non-surgical management to a surgical modality has always been a challenge. However, many studies on endoscopic nasopharyngectomy have proven it to be a reliable form of treatment with an excellent outcome. Since 2007, in Sarawak General Hospital, six cases of endoscopic nasopharyngectomy for locally recurrent NPC have been performed with encouraging results.
Traditional open approaches to the nasopharynx either provide limited access and risk significant morbidity. Here we describe our experience with endoscopic resection of nasopharyngeal tumours. Retrospective chart review was performed for all patients who underwent endoscopic nasopharyngeal resection from September 1993 to January 2007 at a tertiary rhinology centre. Six patients underwent endoscopic nasopharyngectomy for tumours arising from or involving the nasopharynx. The mean age was 49.8 years (range 23 - 70). The sex distribution was five males and one female. Four tumours were malignant and two were benign. The mean disease-free and overall survival for malignant tumors was 90.75 months (range 66 - 120 months). None of the benign tumors recurred. The endoscopic nasopharyngectomy technique may be successfully used for resection of tumors arising from or involving the nasopharynx with good efficacy and a decrease in morbidity when compared to open approaches.
Nasopharyngeal carcinoma (NPC) is a cancer which is common in Asia. We report the establishment and early results of a multi-institutional prospective study of nasopharyngeal carcinoma, which seeks to systematically collect data as well as blood and tumour tissue samples from patients diagnosed with nasopharyngeal cancer at six centres in Malaysia. A total of 484 confirmed NPC cases were reported from the six participating centres between 1st July 2007 and 29th February 2008. Of these, 225 were newly diagnosed cases, 53 were recurrent cases and 206 were in remission at the time of reporting. Amongst the newly diagnosed cases, the most common presenting symptom was the presence of neck lumps (42%). Ophthalmo-neurologic symptoms were the presenting symptoms of 11% of the new cases. The majority of cases (75%) presented at stage III/IV.
Malignant melanocytic melanoma is a rare sinonasal malignancy. We present a case report of an elderly lady who presented with epistaxis and intranasal polyps. Computed tomography revealed soft tissue mass in the oropharynx, nasopharynx, left ethmoid and entire maxillary sinus. The mass was removed via endoscopic medial maxillectomy. Histopathology examination revealed sinonasal melanocytic malignant melanoma. At present 17 months postoperatively she is symptom free with no recurrence and under regular follow up.
Nasopharyngeal carcinoma (NPC) is a rare disease in children. Children with NPC almost always have the undifferentiated variant of the disease, which is associated with advanced locoregional and distant metastasis. We report two cases to illustrate that high index of suspicion is necessary to diagnose NPC in children especially those with atypical presentation of otitis media with effusion (OME).
Reported cases of acquired posterior choanal atresia are very few in the English literature. A case of acquired posterior choanal atresia post radiotherapy is reported which was treated by endonasal endoscopic repair using microdebrider with untoward effect.
Hemangiopericytoma is a very rare angiogenic tumor. In the nasal cavity, it can be considered malignant. It occurs in various parts of the body but those in the nasal cavity account for only 5% of total cases. Less than 200 cases have been reported worldwide involving the nose and paranasal sinuses. Due to its rarity a proper line of management has not been established to tackle this tumour. This article highlights two cases of hemangiopericytoma (HPC), one in an adult and the other in a child, presenting as an intranasal mass.
Nasopharyngeal carcinoma (NPC) is a common cancer in Malaysia. The clinical presentation in Sarawak has not been well documented. A retrospective review of 213 selected NPC cases was undertaken on the clinical records in Sarawak General Hospital, Sarawak, from June 1999 to June 2003. There were 116 patients in Kuching and 97 in Serian. There were twice as many males as females. The youngest patient was 16 and the oldest 88 years old with a mean age of 51 years. The four most common symptoms in order of frequencies were cervical lymphadenopathy, epistaxis, hearing loss and diplopia. 80.8% of the patients presented with cervical lymphadenopathy and about 85% of the patients presented in the advanced stages. Very small percentages of the patients were found to have single presenting symptoms of epistaxis (2.4%) and hearing loss (0.5%).
We present a case of nasopharyngeal carcinoma complicated with hyperleucocytosis. After ruling our other causes we concluded that the hyperleucocytosis was due to paraneoplastic leukemoid reaction (PLR). The overall survival was 15 months which is rare among patients with PLR.
Keywords: Sabah
We report a rare tumour of the nasopharynx- papillary adenocarcinoma. This is usually of low grade and certainly in out patient it behaved so. It is even rarer to have this tumour in a patient with Turner's syndrome in whom there is a high incidence of gynaecological malignancy. It has not previously been documented and the occurrence in this patient is probably coincidental.