C. A. van Hasselt

Increase in circulating Foxp3+CD4+CD25high regulatory T cells in nasopharyngeal carcinoma patients

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus-associated disease with high prevalence in Southern Chinese. Using multiparametric flow cytometry, we identified significant expansions of circulating naïve and memory CD4+CD25high T cells in 56 NPC patients compared with healthy age- and sex-matched controls. These were regulatory T cells (Treg), as they overexpressed Foxp3 and GITR, and demonstrated enhanced suppressive activities against autologous CD4+CD25− T-cell proliferation in functional studies on five patients. Abundant intraepithelial infiltrations of Treg with very high levels of Foxp3 expression and absence of CCR7 expression were also detected in five primary tumours. Our current study is the first to demonstrate an expansion of functional Treg in the circulation of NPC patients and the presence of infiltrating Treg in the tumour microenvironment. As Treg may play an important role in suppressing antitumour immunity, our findings provide critical insights for clinical management of NPC.

Oestrogen mediates the growth of human thyroid carcinoma cells via an oestrogen receptor – ERK pathway

Abstract.  Objectives: Although thyroid cancer occurs much more frequently in females, the role of sex hormones in thyroid carcinogenesis is unknown. In this study, it has been investigated how 17β‐oestradiol (E2) influenced proliferation and growth of thyroid cancer cells. Materials and Methods: Cell proliferation and its related molecules were examined in thyroid papillary carcinoma cells (KAT5), follicular thyroid carcinoma cells (FRO) and anaplastic carcinoma cells (ARO). Levels of oestrogen receptor (ER) α and β were regulated by their agonists (PPT and DPN), antagonists and siRNA. Results: E2 promoted cell proliferation. Such an effect was positively related to ERα but negatively to ERβ; PPT enhanced cell proliferation while DPN inhibited it. PPT increased Bcl‐2 expression while DPN decreased it. DPN also elevated Bax expression. PPT elevated the level of phosphorylated extracellular signal‐regulated kinase 1/2 (pERK1/2), suggesting a positive role of ERK1/2 in E2‐induced cell proliferation. Knockdown of ERα significantly attenuated E2‐mediated Bcl‐2 and pERK1/2 expression. In contrast, knockdown of ERβ markedly enhanced them. Conclusions: Oestrogen stimulates proliferation of thyroid cancer cells, associated with increase in Bcl‐2 and decrease in Bax levels in an ERK1/2‐related pathway. Imbalance between ERα and ERβ may contribute to thyroid carcinogenesis.

Diagnosis of peritonsillar infections : a prospective study of ultrasound, computerized tomography and clinical diagnosis

Peritonsillar infections include cellulitis and abscess (quinsy). Clinical diagnosis is often supplemented by diagnostic drainage (aspiration or incision) in an effort to distinguish abscess from cellulitis. In a prospective study of 14 patients we have shown that clinical impression alone is unreliable (sensitivity 78 per cent, specificity 50 per cent). Computerized tomography (CT) (sensitivity 100 per cent, specificity 75 per cent) and intraoral ultrasound (sensitivity 89 per cent, specificity 100 per cent) are much more reliable. We propose that intraoral ultrasound could play a useful role in the clinical assessment of peritonsillar infections helping to improve accuracy in distinguishing abscesses from cellulitis.

Induction of thyroid papillary carcinoma cell proliferation by estrogen is associated with an altered expression of BCL-XL

PURPOSEOne of the features of thyroid carcinoma is its predilection for women of reproductive age relative to men. An increased risk has also been documented in women who have used estrogens for gynecologic reasons. The aim of this study was to explore the mechanism by which sex hormones contribute to the development of thyroid carcinoma, which is not well understood at present. MATERIALS AND METHODSIn this study, we investigated the effects of estradiol and testosterone on cell proliferation in a human thyroid papillary carcinoma cell line (KAT5) by MTT assay. We also studied the expression of estrogen receptors and the levels of anti-apoptotic Bcl-xL protein, pro-apoptotic Bax protein, and messenger RNA in the cells by Western blot and reverse transcriptase polymerase chain reaction analysis. RESULTSThe results showed that estradiol promotes cell proliferation when compared with cells treated with testosterone and untreated cells, and that the growth-promoting effect of estradiol was attenuated by tamoxifen. The expression of Bcl-xL was markedly increased in a dose-dependent manner, resulting in an elevated ratio of Bcl-xL to Bax. DISCUSSIONWe conclude that estradiol promotes KAT5 cell proliferation and that the underlying mechanism may be associated with up-regulation of Bcl-xL expression. The data provide insight into the molecular mechanism underlying the epidemiologic data that shows a two- to threefold increased prevalence of thyroid carcinoma in women relative to men. From the therapeutic point of view, the finding that estradiol enhances anti-apoptotic signaling pathways may be significant in the search for novel prevention and treatment strategies of thyroid carcinomas.

Heme oxygenase-1 protects against apoptosis induced by tumor necrosis factor-α and cycloheximide in papillary thyroid carcinoma cells

Heme oxygenase‐1 (HO‐1) plays a role in the resistance to apoptosis of several types of cells, but its role in the development of thyroid cancer is unknown. In this study, we investigated the regulation of HO‐1 in human papillary thyroid carcinoma cells (KAT5). The results show that HO‐1 is significantly induced by hemin and cadmium. In addition to inducing HO‐1, hemin and cadmium also cause a rise in the levels of p21, a cyclin‐dependent kinase inhibitor. Cells with increased levels of HO‐1 and p21 were more resistant to apoptotic stimuli than cells with normal levels. The cells resistant to apoptosis also displayed an increased arrest at the G0/G1 phase of the cell‐cycle. The induced levels of HO‐1 and p21 were significantly reduced by p38 mitogen‐activated protein kinase (p38 MAPK) and extracellular‐regulated kinase (ERK) inhibitors. More importantly, KAT5 cells regained their sensitivity to apoptotic stimuli after they were treated with these kinase inhibitors, indicating that p38 MAPK and ERK are required for the resistance to apoptosis conferred by HO‐1. Furthermore, we demonstrated that increased levels of HO‐1 and p21 expression are associated with an increase in the activity of NF‐kappaB and that inhibiting NF‐kappaB leads to a block in the induction of HO‐1 and p21. In summary, this study reveals that an increase in the level of HO‐1 markedly reduces the sensitivity of papillary thyroid carcinoma cells to apoptotic stimuli. The HO‐1 pathway of apoptosis resistance is associated with an increase in the levels of p21, involves a p38 MAPK and ERK‐mediated mechanism and can be suppressed by inhibiting NF‐kappaB.

The contributions of oestrogen receptor isoforms to the development of papillary and anaplastic thyroid carcinomas.

Oestrogen (E2) is known to promote the proliferation of thyroid papillary carcinoma cells (KAT5). However, the molecular mechanism responsible is not well understood. In the study reported herein, the localization of ER alpha (ERα) and beta (ERβ) in KAT5 and anaplastic carcinoma cells (FRO) was studied by immunofluorescence staining and by immunoblotting the proteins in subcellular fractions. Cell proliferation and apoptosis were also determined together with the expression of relevant proteins. The pattern of the subcellular localization of ERα and ERβ differed between papillary and anaplastic cancer. Upon E2 treatment, the level of ERα increased in the nuclei of papillary cancer cells but ERβ remained unchanged. The level of mitochondrial ERβ surpassed that of ERα in anaplastic cancer cells. The different locations of ERα and ERβ in KAT5 and FRO agreed with the finding that E2 promoted the proliferation of KAT5 but inhibited or did not affect that of FRO cells, and with the proposed functions of these two receptors. E2 inhibited the level of Bax in the mitochondria of papillary cancer, followed by a decrease of cytochrome c and/or apoptosis‐inducing factor (AIF) release from the mitochondria into the cytosol. However, in anaplastic cancer, E2 promoted the expression of Bax in the mitochondria and the release of cytochrome c and/or AIF from mitochondria into the cytosol. Our results may explain the differences in epidemiology and responses to anti‐tumour therapy between papillary and anaplastic cancer in terms of the subcellular localization of ER isoforms. In conclusion, the findings provide evidence to support the observation that E2 is an important factor in the development of thyroid cancer. The subcellular localization of ERα and ERβ may account for the different pathogenesis of thyroid papillary and anaplastic cancers. Copyright

Pigmented villonodular synovitis of the temporomandibular joint

The first case of pigmented villonodular synovitis of the temporomandibular joint in a Chinese patient is reported. The clinicopathological features are described and the presentation as a parotid mass is emphasized. This rare tumour requires a high clinical suspicion for diagnosis. For removal, meticulous dissection of tumour and facial nerve is necessary.

The lateral neck radiograph in suspected impacted fish bones — Does it have a role?

A double blind trial, using lateral neck radiographs of 100 patients with proven impacted fish bones and 100 normal cases, was conducted to assess the sensitivity, specificity and positive predictive value of radiography for impacted fish bones. Values of 25.3%, 86.3% and 72.7% respectively were obtained. The results are correlated to the clinical findings and reasons for the poor performance of radiography are discussed. It is recommended that routine radiography for suspected impacted fish bones should be abandoned.

Calcium-mediated activation of PI3K and p53 leads to apoptosis in thyroid carcinoma cells.

Abstract.The molecular mechanism responsible for cadmium-induced cell death in thyroid cancer cells (FRO) is unknown. We demonstrated that apoptosis of FRO cells induced by cadmium was concentration and time dependent. Cadmium caused the rapid elevation of intracellular calcium and induced phosphorylation of Akt, p53, JNK, ERK and p38. Inhibition of PI3K/Akt attenuated the cadmium-induced apoptosis, but the inhibition of JNK inhibitor, ERK or p38 aggravated it, indicating that activation of PI3K/Akt was a pro-apoptosis signal in response to cadmium treatment, whereas the activation of stress-activated protein kinase JNK, ERK and p38 functioned as survival signals to counteract the cadmium-induced apoptosis. Buffering of the calcium response attenuated mitochondrial impairment, recovered the cadmium-activated Akt, p53, JNK, ERK and p38, and subsequently blocked the apoptosis. These results suggested that apoptosis induced by cadmium in FRO cells was initiated by the rapid elevation of intracellular calcium, followed by calcium-mediated activation of PI3K/Akt and mitochondrial impairment.

The use of personal cassette players among youths and its effects on hearing.

To assess the prevalence of use of Personal Cassette Players (PCP) among youths in a residential community in Hong Kong, we interviewed 487 youths aged 15-24 years who attended various activities in eight Youth Centres in Shatin, Hong Kong. 394 (81%) reported using the Personal Cassette Player regularly. The mean duration of PCP use was 2.8 years with a median of 2 years. The mean time of listening to PCP was 4.5 hours per week. We further examined 124 subjects by otoscopy and of the 103 otoscopically normal individuals, audiometric tests were performed. Among the 78 PCP users and 25 non-users, no significant difference in the mean hearing threshold was observed for the frequencies tested. The mean ear canal sound level was 70.4 dBA. Four subjects were habitually exposed to sound levels higher than 85 dBA. One was exposed to 116 dBA and was found to have a 4000 Hz dip on his audiogram, suggestive of noise-induced hearing loss. In general, despite the high prevalence of PCP use, most youths used their PCP at relatively safe sound levels with low risk of hearing loss. However, education directed towards the youth with respect to the potential hazard on hearing due to improper and prolonged use of PCP is still warranted.