Transnasal endoscopic orbital decompression: 15-year clinical experience in Southern Taiwan.

BACKGROUND/PURPOSE: To present the results and evaluate the efficacy of endoscopic transnasal orbital decompression for dysthyroid orbitopathy. METHODS: Retrospective chart review of patients who underwent endoscopic transnasal orbital decompression from 1996 to 2010 in one institution. We included 42 orbits of 25 patients. Preoperative and postoperative examinations included visual acuity, Hertel exophthalmometry, tonometry, exposure keratitis, and diplopia. The measurements of outcome depend on proptosis reduction, intraocular pressure reduction, and visual acuity improvement of 42 orbits of 25 patients. RESULTS: There were no surgical complications for the 42 orbital decompressions except one patient experienced cerebrospinal fluid leak during the operation. Mean proptosis reduction in all orbits was 1.93 ± 0.25 (mean ± standard deviation, p < 0.01) after 1 month postoperatively and 2.07 ± 0.29 (p < 0.01) after 3 months postoperatively. An average reduction of intraocular pressure was 4.40 ± 0.72 (p < 0.01) and 4.38 ± 0.80 (p < 0.01) respectively after 1 and 3 months postoperatively. Visual acuity increased from a preoperative average of 0.45 ± 0.34 to 0.66 ± 0.36 and 0.70 ± 0.35 after 1 and 3 months postoperatively. In addition, postoperative relief of exposure keratitis is also noted. CONCLUSION: The transnasal orbital decompression procedure has statistically significant improvements in proptosis, intraocular pressure, and visual acuity. The procedure has obvious benefit in relieving exposure keratitis. Furthermore, there are favorable cosmetic results and rare complications.

Effects of Antrodia camphorata extracts on the viability, apoptosis, [Ca2+]i, and MAPKs phosphorylation of OC2 human oral cancer cells.

The effect of Antrodia camphorata (AC) on human oral cancer cells has not been explored. This study examined the effect of AC on the viability, apoptosis, mitogen-activated protein kinases (MAPKs) phosphorylation and Ca2+ regulation of OC2 human oral cancer cells. AC at a concentration of 25 microM induced an increase in cell viability, but AC at concentrations > or = 50 microg/ml decreased viability in a concentration-dependent manner. AC at concentrations of 100-200 microg/ml induced apoptosis in a concentration-dependent manner as demonstrated by propidium iodide staining. AC (25 microg/ml) did not alter basal [Ca2+]i, but decreased the [Ca2+]i increases induced by ATP, bradykinin, histamine and thapsigargin. ATP, bradykinin, and histamine increased cell viability whereas thapsigargin decreased it. AC (25 microg/ml) pretreatment failed to alter ATP-induced increase in viability, potentiated bradykinin-induced increase in viability, decreased histamine-induced increase in viability and reversed thapsigargin-induced decrease in viability. Immunoblotting suggested that AC induced phosphorylation of ERK and JNK MAPKs, but not p38 MAPK. Collectively, for OC2 cells, AC exerted multiple effects on their viability and [Ca2+]i, induced their ERK and JNK MAPK phosphorylation, and probably evoked their apoptosis.

Survey of the frequency of olfactory dysfunction in Taiwan.

BACKGROUND: Olfactory function is related to the scrutiny of environmental dangers and the tasting of food. However, olfactory dysfunction is not as distinctive as visual loss and may go unnoticed, especially when olfactory function deteriorates slowly. Most studies have used either questionnaires or relatively insensitive tests to assess olfactory dysfunction. Therefore, the objective of this study was to evaluate the frequency of olfactory dysfunction in Taiwan. METHODS: A total of 211 participants were recruited randomly from the community, factories or offices in Taichung City, Taiwan from April 2005 to March 2006. Age ranged from 19 to 89 years (mean age, 43.3 +/- 12.7 years). All participants filled in questionnaires about sociodemographic data, self-rated olfactory function and impact on quality of life. The olfactory test was performed with identification task of the "Sniffin' Sticks" olfactory function test. RESULTS: The frequency of olfactory dysfunction in our series was 12.3%. There was a statistically significant difference in the ages of the normal and olfactory dysfunction groups (t test, p < 0.0001). The incidences of parosmia and phantosmia in the 211 participants were 10% and 30.8%, respectively. Most subjects did not rate their olfactory function well. There was no correlation between olfactory function and self-ratings of impact of olfactory function on quality of life. CONCLUSION: Our present results provide preliminary data and clinical experience regarding the frequency of olfactory dysfunction in Taiwan. Future modifications and suggestions for the study of the prevalence of olfactory dysfunction are also mentioned.

An organizing hematoma in the parapharyngeal space.

Organizing hematomas occur in many locations and simulate neoplasms. They all have similar structure, with a central mass of blood, a wall of granulation tissue, and dense, fibrous tissue at the periphery. There have been sporadic reports of organizing hematoma not only in soft tissue but also in brain, adrenal gland, lung and maxillary sinus. We report a case of nontraumatic head and neck organizing hematoma---one that occurred in the parapharyngeal space (PPS), a site that has not been previously reported. By doing so, since idiopathic organizing hematoma may occur, we hope to promote awareness and consideration of organizing hematoma in the differential diagnosis of tumor in the post-styloid compartment of the PPS, especially in patients with history of trauma or bleeding tendency.

Primary tumor volume calculation as a predictive factor of prognosis in nasopharyngeal carcinoma.

CONCLUSIONS: Primary tumor volume (PTV) has a close relationship with survival rates of patients with nasopharyngeal carcinoma (NPC) who were treated with concurrent chemoradiotherapy (CCRT) or radiotherapy. Besides the current AJCC staging system, measurement of PTV may be needed to predict prognosis of NPC and adjust treatment strategy. OBJECTIVES: We conducted a retrospective study to elucidate the effect of PTV on treatment outcomes in patients with NPC who were treated with CCRT or radiotherapy. PATIENTS AND METHODS: A total of 66 patients with newly diagnosed NPC were enrolled in this study. Computed tomography (CT)-derived or magnetic resonance imaging (MRI)-derived PTV was calculated. The correlation between AJCC disease stage, PTV, and disease-specific survival was analyzed. Correlations between different prognostic factors were assessed using a Cox regression model. RESULTS: The median PTV for the whole series was 12.01 ml (range 1.25-166.58 ml). The median PTV was 3.45 ml in T1 disease, 7.96 ml in T2 disease, 17.95 ml in T3 disease, and 64.73 ml in T4 disease. Disease stage and T stage carried no prognostic significance (p=0.25 and p =0.30, respectively). Four categories of PTV (<12.5 ml, 12.5-25 ml, 25-50 ml and >50 ml) had prognostic significance (p=0.02). Survival analysis demonstrated a significant difference in overall survival with larger tumor volume (risk ratio 5.447; p=0.044).

Primary tumor volume of nasopharyngeal carcinoma: significance for recurrence and survival.

BACKGROUND: Primary tumor volume (PTV) is known to be a significant prognostic factor in malignant tumor. There have been several studies of nasopharyngeal carcinoma (NPC) relating tumor volume to treatment outcome. Our study was designed to evaluate the effect of PTV on treatment outcomes in NPC treated with radiotherapy (RT)/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant chemotherapy. METHODS: We retrospectively reviewed 100 cases with newly diagnosed NPC who were treated with RT/CCRT or CCRT with adjuvant chemotherapy from 2002 to 2006. Magnetic resonance imaging-derived PTV was calculated using the summation-of-area technique. Kaplan-Meier plots and the log-rank test were used to estimate tumor recurrence (locoregional, distant, or both) and overall survival. Cox proportional hazards regression analysis was used to assess the prognostic impact of PTV. RESULTS: The median PTV was 12.94 mL. PTV remained an independent prognostic factor for distant metastasis (hazard ratio [HR], 1.04; p=0.03), for any relapse (HR, 1.04; p=0.02), and for overall survival (HR, 1.09; p<0.001) in multivariate analysis. In the large tumor volume group (PTV>15 mL), patients' metastasis-free survival rates, with and without adjuvant chemotherapy, were 100% and 68.3%, respectively (p=0.002). Their 3-year recurrence-free survival rates, with and without adjuvant chemotherapy, were 94.1% and 69.6%, respectively (p=0.006). In the small tumor volume group (PTV 15 mL) was associated with more recurrence and poor survival rate, and it was suggested that these high-risk patients should benefit from CCRT followed by adjuvant chemotherapy.

Thimerosal-induced apoptosis in human SCM1 gastric cancer cells: activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation.

Thimerosal is a mercury-containing preservative in some vaccines. The effect of thimerosal on human gastric cancer cells is unknown. This study shows that in cultured human gastric cancer cells (SCM1), thimerosal reduced cell viability in a concentration- and time-dependent manner. Thimerosal caused apoptosis as assessed by propidium iodide-stained cells and caspase-3 activation. Although immunoblotting data revealed that thimerosal could activate the phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal protein kinase, and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Thimerosal also induced [Ca2+](i) increases via Ca2+ influx from the extracellular space. However, pretreatment with (bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate)/AM, a Ca2+ chelator, to prevent thimerosal-induced [Ca2+](i) increases did not protect cells from death. The results suggest that in SCM1 cells, thimerosal caused Ca2+-independent apoptosis via phosphorylating p38 MAPK resulting in caspase-3 activation.

Phospholipase A2-independent Ca2+ entry and subsequent apoptosis induced by melittin in human MG63 osteosarcoma cells.

Melittin, a peptide from bee venom, is thought to be a phospholipase A(2) activator and Ca(2+) influx inducer that can evoke cell death in different cell types. However, the effect of melittin on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and viability has not been explored in human osteoblast-like cells. This study examined whether melittin altered [Ca(2+)](i) and killed cells in MG63 human osteosarcoma cells. [Ca(2+)](i) changes and cell viability were measured by using the fluorescent dyes fura-2 and WST-1, respectively. Melittin at concentrations above 0.075 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was abolished by removing extracellular Ca(2+). Melittin-induced Ca(2+) entry was confirmed by Mn(2+) quenching of fura-2 fluorescence at 360 nm excitation wavelength which was Ca(2+)-insensitive. The melittin-induced Ca(2+) influx was unchanged by modulation of protein kinase-C activity with phorbol 12-myristate 13-acetate (PMA) and GF 109203X, or inhibition of phospholipase A(2) with AACOCF(3) and aristolochic acid; but was substantially inhibited by blocking L-type Ca(2+) channels. At concentrations of 0.5 microM and 1 microM, melittin killed 33% and 45% of cells, respectively, via inducing apoptosis. Lower concentrations of melittin failed to kill cells. The cytotoxic effect of 1 microM melittin was completely reversed by pre-chelating cytosolic Ca(2+) with BAPTA. Taken together, these data showed that in MG63 cells, melittin induced a [Ca(2+)](i) increase by causing Ca(2+) entry through L-type Ca(2+) channels in a manner independent of protein kinase-C and phospholipase A(2) activity; and this [Ca(2+)](i) increase subsequently caused apoptosis.

Desipramine-induced Ca2+ movement and cytotoxicity in PC3 human prostate cancer cells.

The effect of the antidepressant desipramine on intracellular Ca(2+) movement and viability in prostate cancer cells has not been explored previously. The present study examined whether desipramine could alter Ca(2+) handling and viability in human prostate PC3 cancer cells. Cytosolic free Ca(2+) levels ([Ca(2+)](i)) in populations of cells were measured using fura-2 as a probe. Desipramine at concentrations above 10 microM increased [Ca(2+)](i) in a concentration-dependent manner. The responses saturated at 300 microM desipramine. The Ca(2+) signal was reduced by half by removing extracellular Ca(2+), but was unaffected by nifedipine, nicardipine, nimodipine, diltiazem or verapamil. In Ca(2+)-free medium, after treatment with 300 microM desipramine, 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) failed to release Ca(2+) from endoplasmic reticulum. Conversely, desipramine failed to release more Ca(2+) after thapsigargin treatment. Inhibition of phospholipase C with U73122 did not affect desipramine-induced Ca(2+) release. Overnight incubation with 10-800 microM desipramine decreased viability in a concentration-dependent manner. Chelation of cytosolic Ca(2+) with BAPTA did not reverse the decreased cell viability. Collectively, the data suggest that in PC3 cells, desipramine induced a [Ca(2+)](i) increase by causing Ca(2+) release from endoplasmic reticulum in a phospholipase C-independent fashion and by inducing Ca(2+) influx. Desipramine decreased cell viability in a concentration-dependent, Ca(2+)-independent manner.

Clinicopathologic evaluation of prognostic factors for squamous cell carcinoma of the buccal mucosa.

BACKGROUND: The purpose of this research was to evaluate the prognostic significance of clinicopathologic variables on the survival rate for squamous cell carcinoma of the buccal mucosa (BMSCC). We analyzed the outcomes of surgical therapy for this aggressive cancer and compared these results with those in the literature. METHODS: We reviewed the medical charts of 172 patients treated in our institution between 1990 and 2005. There were 22 patients excluded from our studies: 20 patients with advanced tumors who received no treatment or palliative treatment, and 2 patients who had received preoperative radiotherapy (RT). The remaining 150 patients were treated with surgeries and among them, 56 patients had undergone postoperative RT. The influence of clinicopathologic factors on the survival rate was analyzed with the Kaplan-Meier method and log-rank test. Multivariate analysis was assessed with Cox's regression model. RESULTS: There were 148 males and 2 females, with a mean age of 53.5 years. The prevalence rate of habitual betel quid chewing documented in charts among 113 patients was 75%. The 5-year overall survival rate and disease-specific survival rate for all patients were 64% and 69%, respectively. For patients with stages I, II, III, and IV disease, the 5-year disease-specific survival rates were 90%, 77%, 52%, and 47%, respectively (p<0.001). According to the multivariate analysis, the pathologic staging and histologic grading of the tumor were independently the important prognostic factors affecting survival rate. There were 80 patients who developed locoregional recurrence in lymph nodes in the follow-up diagnoses. Distant metastases occurred in 14 patients, with 11 of them also having locoregional recurrence. The distant metastases were found in the lungs (8/14), T-spine (3/14), liver (2/14) and brain (1/14). CONCLUSION: Pathologic stage and histologic grade are the most important prognostic factors.

Diffuse large B-cell lymphoma of the cerebellopontine angle in a patient with sudden hearing loss and facial palsy.

Primary lymphoma of the cerebellopontine angle (CPA) is rare in the central nervous system. To our knowledge, there have only been 14 cases reported worldwide so far. Here, we report our findings in a 57-year-old man, who presented with bilateral sudden hearing loss followed by left facial palsy within 1 month. Radiologic study and magnetic resonance imaging showed a homogeneous enhancing mass, 1.6 x 0.5 x 1.1cm in size, in the left CPA cistern region with mild extension to the left internal auditory canal. The tumor was removed through left retromastoid craniectomy, and the histopathologic diagnosis of the tumor was confirmed as diffuse large B-cell type malignant lymphoma. After a series of tumor surveys, there was no evidence of other original lymphoma. The patient was treated with chemotherapy (including intra-Ommaya injection with methotrexate and Ara-C and systemic injection with vincristine, methotrexate and ifosfamide) for the primary CPA lymphoma. He was still alive 19 months after the initial treatment.

Endoscopic sinus surgery under navigation system--analysis report of 79 cases.

BACKGROUND: Functional endoscopic sinus surgery (FESS) is the most popular method for treating medicine-refractory sinonasal disease. However, there are some pitfalls with this technique that can result in serious complications. Under the assistance of a navigation system, surgeons can overcome such problems. This study aimed to evaluate the efficacy of FESS aided by a navigation system. METHODS: There were 79 patients who underwent FESS under the assistance of a navigation system in our department between September 2004 and September 2005. Data on preoperative setup time, accuracy of the navigation system, operative time, and amount of blood loss during the operation were collected and analyzed. RESULTS: Mean preoperative setup time and mean operative time were 10.6 minutes and 112.3 minutes, respectively. The mean number of paranasal sinuses operated on was 5.8. The mean accuracy of the navigator system was 1.08 mm. Mean blood loss was 102.5 mL. Compared with data collected 2 years ago, preoperative setup time and operative time had both shortened. In addition, the number of operated paranasal sinuses had increased. This indicates that operative skill had improved. Moreover, operative time, amount of blood loss during the operation, and number of operated paranasal sinuses presented positive associations and significant differences (p < 0.05). No major complications such as blindness or cerebral spinal fluid leakage were noted. CONCLUSION: The characteristics of FESS aided by a navigation system include: (1) being able to pilot the relative positions of the operative instruments correctly in 3 dimensions; (2) being able to remove lesions more thoroughly; and (3) its inability to disclose the positions of vessels. As the number of patients we operated on increased, operative time was reduced. On the other hand, blood loss increased when the operations became more aggressive. However, performing FESS with the assistance of a navigation system is a safe way to treat patients with chronic paranasal sinusitis.

Spindle cell carcinoma of the oral cavity and oropharynx: factors affecting outcome.

BACKGROUND: Spindle cell carcinoma (SpCC) is considered to be a rare variant of squamous cell carcinoma (SCC). The behavior of such tumors is unclear. The aim of this study was to elucidate the treatment and outcome of oral and oropharyngeal SpCC. METHODS: All the medical records of patients with the diagnosis of SpCC in the oral cavity and oropharynx in our hospital from 1994 to 2005 were reviewed. The clinical features, treatments and survival of the patients were evaluated. RESULTS: Within the 11-year study period, 18 patients were diagnosed with oral and oropharyngeal SpCC. There were 3 cases of AJCC (American Joint Committee on Cancer) stage I, 3 of stage II, 2 of stage III, 9 of stage IV, and 1 case without definite staging. Twelve patients died of their diseases. The median overall survival time was 8.89 months. The 1-year overall survival rate was 36.7% and the 3-year overall survival rate was 27.5%. In the early stage group, the 1-year and 3-year survival rates were both 100%. In the late stage group, the 1-year survival rate was 9%, and the 3-year survival rate was 0%. The factors influencing overall survival were tumor grade, lymph nodes, metastasis, stage, vascular invasion and distant recurrence. A high local recurrence rate (73.3%) and distant metastasis rate (33.3%) were observed. CONCLUSION: The behavior of SpCC seems to be more aggressive than that of SCC at a similar stage. Setting wider safety margins (> 2 cm) during surgical intervention is suggested. In the case of locoregional recurrence, salvage operation showed some benefit. Seeking an effective chemotherapy protocol is important for the control of distant recurrence.

Features of a giant cell tumour of the parotid gland: A case report.

A giant cell tumour (GCT) is a benign tumour that commonly arises in the distal end of the long bones. Extraosseous GCTs have been reported in a number of organs, but it is rare for a GCT to present in the parotid gland. Therefore, primary GCTs of the parotid gland (GCTPs) are extremely rare. Although GCTPs have been identified as benign soft-tissue tumours, they have a highly malignant potential and poor prognosis. In the present case, we report a 58-year-old male patient presenting with non-tender mass over the left preauricular area for 11 months. The final pathology report revealed a rare case of a GCTP that was treated by parotidectomy and adjuvant radiation therapy. The patient had no recurrence after 2 years of follow-up.

Effect of m-3m3FBS on Ca2+ handling and viability in OC2 human oral cancer cells.

The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca2+ concentrations ([Ca2+]i) in OC2 human oral cancer cells is unclear. This study explored whether m-3M3FBS changed basal [Ca2+]i levels in suspended OC2 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. M-3M3FBS at concentrations between 10-60 µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. M-3M3FBS-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and SK&F96365, and by the phospholipase A2 inhibitor aristolochic acid. In Ca2+-free medium, 30 µM m-3M3FBS pretreatment inhibited the [Ca2+]i rise induced by the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin and 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with thapsigargin, BHQ or cyclopiazonic acid partly reduced m-3M3FBS-induced [Ca2+]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 did not alter m-3M3FBS-induced [Ca2+]i rise. At concentrations between 5 and 100 µM m-3M3FBS killed cells in a concentration-dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Propidium iodide staining data suggest that m-3M3FBS (20 or 50 µM) induced apoptosis in a Ca2+-independent manner. Collectively, in OC2 cells, m-3M3FBS induced [Ca2+]i rise by causing inositol 1,4,5-trisphosphate-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-sensitive store-operated Ca2+ channels. M-3M3FBS also induced Ca2+-independent cell death and apoptosis.

Upper airway obstruction caused by bilateral giant tonsilloliths.

Tonsilloliths are rare dystrophic calcifications caused by chronic inflammation of the tonsils. They are usually small and occur on one side. Herein, we report a case involving a 75-year-old man presenting odynophagia and progressive dyspnea for days who was found by computed tomography image to have bilateral giant tonsilloliths. Hyperdensity lesions were found over the tonsillar fossa on both sides. Tonsillectomy was performed leading to immediate relief of symptoms. A review of relevant literature revealed that most patients with tonsilloliths are asymptomatic and need only conservative treatment. Severe symptoms such as dyspnea are extremely rare. Although tonsillolith can be easily diagnosed by computed tomography, otolaryngologists should be careful to differentiate this entity.

Subglottic stenosis induced by extranodal mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma is usually associated with a chronic inflammatory disease or autoimmune disorders from which lymphoid tissue of MALT type arises as a prerequisite for lymphoma proliferation. Primary hematopoietic neoplasms of the larynx are rare. MALT lymphomas of the larynx are believed to arise from preexisting or acquired lymphoid tissue of the upper airway which is documented in the supraglottic region. Therefore, these are mainly located in the supraglottic and glottic areas, with only a few reported in the subglottic region. We report on a 50-year-old woman with a hoarseness, stridor, and developing exertional dyspnea. On indirect laryngoscope, multiple nodular lesions with smooth surface over the subglottis with subglottic steonsis was found. The biopsy confirmed the diagnosis of a MALT lymphoma. We hope to promote awareness and consideration of MALT lymphoma in the differential diagnosis in subglottic steonsis.

The mechanism of sertraline-induced [Ca2+]i rise in human OC2 oral cancer cells.

Effect of sertraline, an antidepressant, on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in human cancer cells is unclear. This study examined if sertraline altered basal [Ca(2+)](i) levels in suspended OC2 human oral cancer by using fura-2 as a Ca(2+)-sensitive fluorescent probe. At concentrations of 10-100 µM, sertraline induced a [Ca(2+)](i) rise in a concentration-dependent fashion. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+) indicating that Ca(2+) entry and release both contributed to the [Ca(2+)](i) rise. Sertraline induced Mn(2+) influx, leading to quench of fura-2 fluorescence suggesting Ca(2+) influx. This Ca(2+) influx was inhibited by suppression of phospholipase A2, inhibition of store-operated Ca(2+) channels or by modulation of protein kinase C activity. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) nearly abolished sertraline-induced Ca(2+) release. Conversely, pretreatment with sertraline greatly reduced the inhibitor-induced [Ca(2+)](i) rise, suggesting that sertraline released Ca(2+) from the endoplasmic reticulum. Inhibition of phospholipase C did not change sertraline-induced [Ca(2+)](i) rise. Together, in human oral cancer cells, sertraline induced [Ca(2+)](i) rises by causing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx via store-operated Ca(2+) channels.

Effect of methoxychlor on Ca2+ handling and viability in OC2 human oral cancer cells.

The effect of the insecticide methoxychlor on the physiology of oral cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) in human oral cancer cells (OC2) by using the Ca(2+)-sensitive fluorescent dye fura-2. Methoxychlor at 5-20 µM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by 70% by removing extracellular Ca(2+). Methoxychlor-induced Ca(2+) entry was not affected by nifedipine, econazole, SK&F96365 and protein kinase C modulators but was inhibited by the phospholipase A2 inhibitor aristolochic acid. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished methoxychlor-induced [Ca(2+)](i) rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 did not alter methoxychlor-induced [Ca(2+)](i) rise. At 5-20 µM, methoxychlor killed cells in a concentration-dependent manner. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that methoxychlor (10 and 20 µM) evoked apoptosis in a concentration-dependent manner. Together, in human OC2, methoxychlor induced a [Ca(2+)](i) rise probably by inducing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via phospholipase A(2)-sensitive channels. Methoxychlor induced cell death that may involve apoptosis.

NAT2 slow acetylation haplotypes are associated with the increased risk of betel quid-related oral and pharyngeal squamous cell carcinoma.

BACKGROUND: NAT2, the most important phase II metabolic enzyme for betel quid (BQ), might modify the risk of BQ-related oral and pharyngeal squamous cell carcinoma (OPSCC) in Taiwan. STUDY DESIGN: PCR-RFLP and TaqMan assay were conducted for genotyping of NAT2 in 172 OPSCC cases and 170 healthy controls who habitually chewed BQ. RESULTS: The genotypic and allelic type of T341C and C481T in NAT2 are associated with the risk of OPSCC. There were linear trends between increased risk of OPSCC and slowness of NAT2 acetylation haplotypes (P = .017), especially for young subjects (P < .001), light BQ chewers (P = .005), light smokers (P = .023), and alcohol drinkers (P = .001). The interactions on risk of OPSCC were found for NAT2 acetylation haplotypes with status of age, BQ chewing, and alcohol drinking. CONCLUSIONS: The NAT2 acetylation haplotypes might be genetic markers for risk of BQ-related OPSCC.