Midline versus paramedian mandibulotomy for tongue cancer surgery: analysis of complications.

Midline and paramedian mandibulotomies both have distinct anatomical and surgical strengths. A retrospective study was performed at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2019 to investigate how the osteotomy site (midline (n = 221) or paramedian (n = 44)) and type (straight, notched, or stair-stepped) affect postoperative and post-radiotherapy complications in patients undergoing wide excision of tongue cancer with flap reconstruction. Midline mandibulotomies were predominantly of the straight osteotomy type, while paramedian mandibulotomies were mostly notched type (P < 0.001). Comparably low elective tooth extraction rates were found in both approaches (P = 0.556). Paramedian mandibulotomy showed a higher osteoradionecrosis rate (P = 0.026), but there was no significance in the sub-analysis of individual types. Paramedian sites were associated with more early infection (P = 0.036) and plate exposure (P = 0.036) than midline sites with the straight osteotomy type, but complication rates did not differ significantly for the notched and stair-stepped types. Paramedian sites (P = 0.020) and notched types (P = 0.006) were associated with higher odds of osteoradionecrosis in the univariable logistic regression analysis, but only the notched type remained significant in the multivariable analysis (P = 0.048). In conclusion, paramedian sites increased the rate of osteoradionecrosis, and correlation with the osteotomy type resulted in more osteoradionecrosis in notched types and more complications in straight paramedian mandibulotomies.

Ptychographic amplitude and phase reconstruction of bichromatic vortex beams.

We experimentally demonstrate that ptychographic coherent diffractive imaging can be used to simultaneously characterize the amplitude and phase of bichromatic orbital angular momenta-shaped vortex beams, which consist of a fundamental field, together with its copropagating second-harmonic field. In contrast to most other orbital angular momentum characterization methods, this approach solves for the complex field of a hyperspectral beam. This technique can also be used to characterize other phase-structured illumination beams, and, in the future, will be able to be extended to other complex fields in the extreme ultraviolet or X-ray spectral regions, as well as to matter waves.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

Single nucleotide polymorphism variants within tva and tvb receptor genes in Chinese chickens.

Avian leukosis is an immunosuppressive neoplastic disease caused by avian leukosis viruses (ALV), which causes tremendous economic losses in the worldwide poultry industry. The susceptibility or resistance of chicken cells to subgroup A ALV and subgroup B, D, and E ALV are determined by the receptor genes tumor virus locus A (tva) and tumor virus locus B (tvb), respectively. Four genetic resistant loci (tva(r1), tva(r2), tva(r3), and tva(r4)) in tva receptor gene and a genetic resistant locus tvb(r) in the tvb receptor gene have been identified in inbred lines of White Leghorn. To evaluate the genetic resistance to subgroup A, B, D, and E ALV, genetic variations within resistant loci in tva and tvb genes were screened in Chinese local chicken breeds and commercial broiler lines. Here, the heterozygote tva(s1/r1) and the resistant genotype tva(r2/r2), tva(r3/r3), and tva(r4/r4) were detected in Chinese chickens by direct sequencing. The heterozygote tva(s1/r1) was detected in Huiyang Bearded chicken (HYBC), Rizhaoma chicken, and commercial broiler line 13 to 15 (CB13 to CB15), with the frequencies at 0.08, 0.18, 0.17, 0.25, and 0.15, respectively. The resistant genotype tva(r2/r2) was detected in Jiningbairi chicken (JNBRC), HYBC, and CB15, with the frequencies at 0.03, 0.08, and 0.06, respectively, whereas tva(r3/r3) and tva(r4/r4) were detected in 19 and 17 of the 25 Chinese chickens tested, with the average frequencies at 0.13 and 0.20, respectively. Furthermore, the resistant genotype tvb(r/r) was detected in JNBRC, CB07, CB12, CB14, and CB15 by pyrosequencing assay, with the frequencies at 0.03, 0.03, 0.11, 0.09, and 0.15, respectively. These results demonstrated that the potential for genetic improvement of resistance to subgroup A, B, D, and E ALV were great both in Chinese local chickens and commercial broilers. This study provides valuable insight into the selective breeding for chickens genetically resistant to ALV.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.

BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research.

BACKGROUND: We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-). METHODS: A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis. RESULTS: A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates. CONCLUSIONS: Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.

Association of HPV infections with second primary tumors in early-staged oral cavity cancer.

OBJECTIVE: The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. MATERIALS AND METHODS: The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests. RESULTS: Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. CONCLUSIONS: There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.

Preoperative circulating C-reactive protein levels predict pathological aggressiveness in oral squamous cell carcinoma: a retrospective clinical study.

OBJECTIVES: Previous studies have demonstrated a relationship between elevated serum C-reactive protein (CRP) levels and shorter survival in cancer patients. Few studies, however, have investigated the role of serum CRP levels in oral squamous cell carcinoma. The present study was conducted to analyze the relationship between preoperative CRP levels, clinicopathologic factors, and prognosis in oral squamous cell carcinoma patients. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PARTICIPANTS: Eighteen oral cavity leukoplakia and 59 oral squamous cell carcinoma patients between November 2006 and November 2009 from the Chang Gung Memorial Hospital. OUTCOME MEASURES: Clinicopathologic parameters, disease-free survival and overall survival were correlated with CRP levels. METHODS: Serum CRP levels were measured preoperatively, and all oral cavity cancer patients underwent curative intent radical surgery with or without postoperative adjuvant therapy. RESULTS: The CRP levels in leukoplakia patients were used to analyze if factors (including diabetes and liver cirrhosis, smoking, alcohol drinking and areca quid chewing) influence CRP levels, and the results demonstrated they were not associated with CRP elevation (> 5.0 mg/L) (P > 0.05). In oral cancer patients, elevated CRP levels were associated with tumor status (P = 0.005), tumor stage (P = 0.054), bone invasion (P = 0.033), lymph node metastasis (P = 0.004) and lymph node extra-capsular spread (P = 0.018). Patients with higher CRP levels showed poorer disease-free survival (log rank test, P < 0.001) and overall survival (log rank test, P = 0.013). CONCLUSIONS: Preoperative serum CRP levels are associated with advanced tumor stage, bone invasion, lymph node metastasis, lymph node extra-capsular spread and patients' survival. CRP is thus potentially a prognostic indicator, but studies with longer follow-up will be needed to confirm its reliability.

Statistical inference for the within-device precision of quantitative measurements in assay validation.

Intermediate precision is one of the most important characteristics for evaluation of precision in assay validation. The current methods for evaluation of within-device precision recommended by the Clinical Laboratory Standard Institute (CLSI) guideline EP5-A2 are based on the point estimator. On the other hand, in addition to point estimators, confidence intervals can provide a range for the within-device precision with a probability statement. Therefore, we suggest a confidence interval approach for assessment of the within-device precision. Furthermore, under the two-stage nested random-effects model recommended by the approved CLSI guideline EP5-A2, in addition to the current Satterthwaite's approximation and the modified large sample (MLS) methods, we apply the technique of generalized pivotal quantities (GPQ) to derive the confidence interval for the within-device precision. The data from the approved CLSI guideline EP5-A2 illustrate the applications of the confidence interval approach and comparison of results between the three methods. Results of a simulation study on the coverage probability and expected length of the three methods are reported. The proposed method of the GPQ-based confidence intervals is also extended to consider the between-laboratories variation for precision assessment.

DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis.

To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer (HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription-polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P=0.009), N stage (P=0.047), overall stage (P=0.011), tumor depth (P=0.009) and extracapsular spread in lymph nodes (P=0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57-21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30-48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.

p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan.

The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) = 1.98; 95% confidence interval (CI), 1.10-3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR = 10.56; 95% CI, 1.23-234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.

Fluoroscopically guided percutaneous gastrostomy with modified gastropexy and a large-bore balloon-retained catheter in patients with head and neck tumors.

PURPOSE: To report on fluoroscopically guided percutaneous gastrostomy (FPG) using a modified gastropexy technique with the insertion of a large-bore balloon-retained gastrostomy catheter in patients with head and neck tumors. MATERIAL AND METHODS: Thirty-four patients with head and neck tumors underwent a modified gastropexy with two T-fasteners followed by the insertion of a 14-F ballooon-retained catheter through a peel-away introducer. The success rate and the complications of the procedures were evaluated at 14 days, 30 days, and 60 days. The complications were classified as: major complications that necessitated intensive and/or surgical treatment; minor complications that could be treated conservatively; and tube-related complications manageable by tube exchange. RESULTS: FPG was technically successful in all cases. There were no major complications, two minor complications where superficial stoma infection was controlled by antibiotics, three minor tube-related complications, all three easily managed by catheter replacement via the original tract. CONCLUSION: FPG with insertion of a large-bore balloon-retained catheter using a modified gastropexy technique is a safe and effective method that creates a feeding access for patients with head and neck tumors and esophageal obstruction. Minor complications can be managed conservatively. FPG may be a good alternative to surgical or percutaneous endoscopic gastrostomy.

Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area cancer prognosis.

Although several studies have found overexpression of epidermal growth factor receptor (EGFR) proteins EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies. We examined the expression and clinical association of these molecules with oral squamous cell carcinoma in an area where betel chewing is prevalent. EGFR and Her-2 proteins were measured in 59 paired (grossly normal and cancer) tissues by an enzyme immunoassy method. The cutoff value for gene overexpression was defined as the level of mean expression in normal tissue plus two s.d. A total of 59% of the patients consumed alcohol, 90% smoked tobacco, and 90% chewed betel quid. Of the patients assayed, 34 (58%) and 24 (41%) had EGFR and Her-2 overexpression, with average 3.5- and 1.5-fold elevations. EGFR overexpression has been shown to be statistically associated with T stage, N stage, overall TMN stage, primary tumour depth, lymph node extra-capsular spread, and poor survival. Her-2 overexpression, however, did not demonstrate a similar association with clinicopathological parameters or therapeutic outcome. On multivariant analysis, EGFR overexpression (P=0.041) and N stage (P=0.024) were the only independent factors for overall survival. These results indicate that the molecular targeting therapy to EGFR may be a treatment for oral cavity cancer in the betel quid-chewing prevalent area.

Characteristics of mutations in the p53 gene in oral squamous cell carcinoma associated with betel quid chewing and cigarette smoking in Taiwanese.

p53 mutations are etiologically associated with the development of oral squamous cell carcinomas (OSCCs) or are associated with exposure to specific carcinogens. In this study, we used PCR-single strand conformation polymorphism and DNA sequencing to analyze the conserved regions of the p53 gene (exons 5-9) in OSCC tumor specimens from 187 patients with varied histories of betel quid, tobacco and alcohol use. Ninety-one of the 187 OSCCs (48.66%) showed p53 gene mutations at exons 5-9. The incidence of p53 mutations was not associated with age, sex, TNM stage, status of cigarette smoking or betel quid chewing. However, alcohol drinkers exhibited a significantly higher incidence (57/101, 56.44%) of p53 mutations than non-users (39.53%, 34/86) (P = 0.02). The effect of alcohol on the incidence of p53 mutations was still statistically significant (RR = 2.24; 95% CI, 1.21-4.15) after adjustment for cigarette smoking and betel quid (BQ) chewing. G:C to A:T transitions were the predominant mutations observed and associated with BQ and tobacco use. Alcohol drinking could enhance these transitions. After adjustment for cigarette smoking and BQ chewing, alcohol drinking still showed an independent effect on G:C to A:T transitions (RR = 2.41; 95% CI, 1.01-5.74). These findings strongly suggest an important contributive role of tobacco carcinogens to p53 mutation in this series of Taiwanese OSCCs and alcohol might enhance these mutagenic effects. As safrole-DNA adducts have been detected in 77% (23/30) of the OSCC tissues from Taiwanese oral cancer patients with a BQ chewing history, we cannot rule out the possibility that safrole or other carcinogens present in the BQ may cause a similar pattern of mutagenesis. Determination of the role of safrole and other carcinogens present in BQ on the pattern of p53 gene mutation in OSCC will require further study.

Physiological adaptation of crop plants to flooding stress.

When crop plants are subjected to soil waterlogging, or an anaerobic condition, their root and shoot systems respond differently. A variety of morphological and anatomical alterations develop in the root system. Reduction of the root respiration rate has been reported in both flooding-tolerant and intolerant species. Besides alcoholic fermentation, several diverse fermentative bypasses take place, which ameliorate the poisoning through excessive accumulation of specific metabolic intermediates. Root systems starved of oxygen are also poor providers of mineral nutrients for both themselves and the shoot systems. Stomatal closure and non-stomatal metabolic alterations are responsible for the reduction of leaf CO2 incorporation. Plant hormones are much involved in regulation of these physiological adaptations.

US-guided needle aspiration and catheter drainage as an alternative to open surgical drainage for uniloculated neck abscesses.

PURPOSE: To prospectively evaluate the effectiveness of ultrasound (US)-guided needle aspiration and catheter drainage as an alternative to open surgical drainage of uniloculated neck abscesses. MATERIALS AND METHODS: Fifteen consecutive patients (11 female, four male; age range from 18 days to 78 years, mean 42.5 y +/- 22.4) diagnosed with deep neck infections associated with uniloculated neck abscesses were treated. The patients were originally scheduled for surgical incision and drainage after a period of unsuccessful treatment with antibiotics. US-guided needle aspiration (in 10 patients) and US-guided catheter drainage (in five patients) were performed under local anesthesia. Open surgical drainage was performed when US-guided drainage procedures failed. RESULTS: Surgical open drainage was avoided in 13 of the 15 patients (87%). An average of 6 mL of pus was obtained in patients in the needle aspiration group and 140 mL of pus was drained by catheter. One patient had a recurrent pyogenic lymphadenitis at the same location and was treated successfully by repeated needle aspiration. No complications occurred in this study. CONCLUSION: In a selected group of patients without imminent airway obstruction, most uniloculated neck abscesses may be managed initially by US-guided needle aspiration and catheter drainage before resorting to open surgical drainage.

Poor prognosis in nasopharyngeal cancer patients with low glucose-6-phosphate-dehydrogenase activity.

Nasopharyngeal carcinoma (NPC) is endemic among well-defined ethnic groups in several world regions, such as Southeastern China and Taiwan. Glucose-6-phosphate-dehydrogenase (G6PD)- deficiency, a sex-linked disorder, is one of the most common enzymopathies in Taiwan. The major role of G6PD is to generate NADPH to protect cells from oxidative damage, which is a major contributing factor to certain degenerative diseases, such as aging and cancer. In view of the coincidence of epidemic distribution of NPC and G6PD deficiency, as well as the house-keeping function of G6PD in cellular oxidative defense, we investigated the correlation of G6PD activity with NPC. The stage of NPC was classified by AJCC (1997) criteria. G6PD levels were determined in 108 NPC male patients and 75 healthy male individuals. The mean G6PD level of NPC patients was 218.9 U/10(12) RBC or 7.53 U/g hemoglobin (Hb), being much lower than in normal individuals (260.6 U/10(12) erythrocytes (RBC) or 8.92 U / gHb). The level of G6PD activity had no correlation with tumor stage or lymph node or distant metastasis, but was significantly correlated with tumor recurrence (P = 0.004 when using G6PD = 130 U/10(12) RBC as cutoff value). These results indicated that low G6PD activity in patients with NPC is associated with poor prognosis.

Structural and functional properties of a Bacillus subtilis temperature-sensitive sigma(A) factor.

Bacillus subtilis DB1005 is a temperature-sensitive (Ts) sigA mutant containing double-amino-acid substitutions (I198A and I202A) on the hydrophobic face of the promoter -10 binding helix of sigma(A) factor. We have analyzed the structural and functional properties of this mutant sigma(A) factor both in vivo and in vitro. Our data revealed that the Ts sigma(A) factor possessed predominantly a multimeric structure which was prone to aggregation at restrictive temperature. The extensive aggregation of the Ts sigma(A) resulted in a very low core-binding activity of the Ts sigma(A) factor and a markedly reduced sigma(A)-RNA polymerase activity in B. subtilis DB1005, suggesting that extensive aggregation of the Ts sigma(A) is the main trigger for the temperature sensitivity of B. subtilis DB1005. Partial proteolysis, tryptophan fluorescence and 1-anilinonaphthalene-8-sulfonate-binding analyses revealed that the hydrophobic face of the promoter -10 binding helix and also the hydrophobic core region of the Ts sigma(A) factor were readily exposed on the protein surface. This hydrophobic exposure provides an important cue for mutual interaction between molecules of the Ts sigma(A) and allows the formation of multimeric Ts sigma(A). Our results also indicate that Ile-198 and Ile-202 on the hydrophobic face of the promoter -10 binding helix are essential to ensure the correct folding and stabilization of the functional structure of sigma(A) factor.

Telomerase activity is frequently found in metaplastic and malignant human nasopharyngeal tissues.

Telomerase is a specialized ribonucleoprotein polymerase that directs the synthesis of telomere repeats at chromosome ends. Accumulating evidence has indicated that telomerase is stringently repressed in normal human somatic tissues but reactivated in cancers and immortal cells, suggesting that reactivation of telomerase plays an important role in carcinogenesis. In this study, the status of telomerase activity in diseased human nasopharyngeal lesions was determined by the telomeric repeat amplification protocol (TRAP). Fifty-four patients participated including 17 inflammation or hyperplasia, eight with squamous metaplasia, and 29 with different stages of carcinomas. Telomerase activity was detected in 1 of 17 (5.9%) inflammatory or lymphoid hyperplastic tissues, 3 of 8 (37.5%) squamous metaplastic, and 25 of 29 (86.2%) carcinoma tissues. The differences in telomerase expression in these groups is statistically significant (P < 0.001). Levels of telomerase activity correlated with tumour stage (P = 0.024). These results suggest that telomerase reactivation plays a role in the carcinogenesis of nasopharyngeal cancer. Since telomerase activity is found in the majority of nasopharyngeal cancers and a subset of metaplasia, this enzyme may be served as a reference to monitoring the status of abnormal nasopharyngeal tissues.