A clinical and experimental study of the nasopharyngeal flora in nasopharyngitis.
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OBJECTIVE: To evaluate the clinical value of CT scan on the early diagnosis of nasopharyngeal masses. METHOD: The results of CT scans and pathological findings to the 59 cases of localized nasopharyngeal masses were summerized. RESULT: Among the 44 cases diagnosed by CT scan as nasopharyngeal carcinoma, their pathological findings revealed 35 cases of nasopharyngeal carcinoma, 2 cases of non Hodgkin's disease, 3 cases of nasopharyngeal tuberculosis, 3 cases of nasopharyngeal lymphadenosis, and 1 case of nasopharyngeal cyst. Among the 11 cases diagnosed by CT scan as local mucal thicking, their pathological findings demonstrated 2 cases of nasopharyngeal carcinoma, 6 cases of chronic inflammation, 1 case of nasopharyngeal tuberculosis, and 2 case of nasopharyngeal cyst. The other 4 cases diagnosed by CT scan as nasopharyngeal fibrohemangioma were confirmed by pathological examination. CONCLUSION: CT scan can correctly reveal nasopharyngeal diseases, and benefit early diagnosis. It shows distinctive advanteges in detecting early stage of submucal nasopharyngeal carcinoma and diagnosing nasopharyngeal fibrohemangioma. But there is limitation in differentiating common nasopharyngeal diseases.
OBJECTIVES: To evaluate the incidence rate of nasopharyngeal carcinoma with dermatomyositis, the influence of dermatomyositis on clinical course, and complications and survival of patients with nasopharyngeal carcinoma after radiotherapy. DESIGN: A retrospective study of 12 patients with nasopharyngeal carcinoma associated with dermatomyositis, with a maximum follow-up of 228 months. SETTING: Academic tertiary referral center. PATIENTS: There were 6441 new patients with nasopharyngeal carcinoma who were seen at the National Taiwan University Hospital, Taipei, during the period from 1970 through 1993. Twelve patients were found to have dermatomyositis. MAIN OUTCOME MEASURE: Clinical manifestations of nasopharyngeal carcinoma with dermatomyositis. RESULTS: Twenty-seven (26%) of 104 patients with dermatomyositis had an associated malignancy. Twelve of these patients were diagnosed as having nasopharyngeal carcinoma. The typical skin manifestation of dermatomyositis was found in all 12 patients. Myopathy occurred in 10 patients. Three patients died of recurrence of nasopharyngeal carcinoma, one died of a second malignancy, one died of upper gastrointestinal bleeding, and one became unavailable for follow-up. The other six patients have had disease-free survival, with a mean follow-up period of 100.5 months (range, 5 to 228 months). The 1-year survival rate was 83.8%, and the 5-year survival rate was 69.4%. CONCLUSIONS: In Taiwan, dermatomyositis is associated with an increased incidence rate of nasopharyngeal carcinoma. A search for nasopharyngeal carcinoma in patients with dermatomyositis should be performed in areas prevalent for nasopharyngeal carcinoma. If present, nasopharyngeal carcinoma can precede, occur concurrently with, or follow the diagnosis of dermatomyositis. Treatment of nasopharyngeal carcinoma may affect myositic or cutaneous disease. The prognosis and survival rates of nasopharyngeal carcinoma remained unaffected by dermatomyositis. No complications were noted owing to the radiotherapy used to treat dermatomyositis.
Undifferentiated nasopharyngeal carcinoma is a result of environmental factors, in particular EBV infection, affecting genetically susceptible individuals. The familial risk of nasopharyngeal carcinoma is among the highest of any malignancy. Whether this susceptibility is restricted to nasopharyngeal carcinoma is unknown as information on the risk of other cancers in relatives is limited. We did a population-based study of the cancer incidence in nasopharyngeal carcinoma families in Greenland, a nasopharyngeal carcinoma-endemic area. Using population-based registers, a cohort of all persons born in Greenland was followed from 1973 to 2002. In this cohort, 134 individuals developed nasopharyngeal carcinoma and their relatives were identified through registers and interviews. Subsequently, the occurrence of cancer was determined by linkage to the population-based cancer register and the risk of cancer in nasopharyngeal carcinoma relatives and nonrelatives compared by relative risks. Among 766 first-degree relatives, the relative risk of nasopharyngeal carcinoma following the family index case was 8.0 [95% confidence interval (95% CI), 4.1-14.0]. Sex and age of the relative or the index case had no modifying effect on the familial risk of nasopharyngeal carcinoma. The relative risks of carcinoma of the salivary glands, 8.4 (95% CI, 2.7-19.5), and uterine cervix, 2.2 (95% CI, 1.1-3.9), were also significantly increased. In families with multiple cases of nasopharyngeal carcinoma, the risk of other cancers than nasopharyngeal carcinoma was further increased. These results indicate that the increased risk of cancer in nasopharyngeal carcinoma families is not restricted to nasopharyngeal carcinoma, but extends to the virally associated cancers of the salivary glands and cervical uteri.
PURPOSE: Chemokine receptors are implicated in metastasis of several malignant tumors. This study was done to evaluate the contribution of chemokine receptors CXCR4 and CCR7 to metastasis of human nasopharyngeal carcinoma. EXPERIMENTAL DESIGN: Reverse transcription-PCR, immunohistochemistry, and flow cytometry were used to evaluate mRNA and protein expression of CXCR4 and CCR7 in nasopharyngeal carcinoma tumor tissues and cell lines. Chemotaxis assays were used to evaluate the function of CXCR4 in nasopharyngeal carcinoma cells. Antisense CXCR4 was used to inhibit receptor expression and to block metastasis of human nasopharyngeal carcinoma cells in vivo in athymic mice. RESULTS: CXCR4 protein was detected in tumor cells in 31 of 40 primary human nasopharyngeal carcinoma and in 13 of 15 lymph node metastases. CXCR4 transcripts were detected in eight CXCR4 protein-positive primary nasopharyngeal carcinoma tissues and seven nasopharyngeal carcinoma cell lines tested. On the other hand, the transcripts for CCR7 were detected only in four primary nasopharyngeal carcinoma tissues and in none of the nasopharyngeal carcinoma cell lines. In functional experiments, metastatic nasopharyngeal carcinoma cell lines that expressed high levels of CXCR4 were found to migrate in response to the CXCR4 ligand SDF-1alpha. Transfection of antisense CXCR4 in metastatic nasopharyngeal carcinoma cells inhibited the expression of CXCR4 and SDF-1alpha-induced cell migration in vitro and reduced the capacity of the tumor cells to form metastasis in the lungs and lymph nodes when injected in athymic mice. CONCLUSION: The expression of functional CXCR4 but not CCR7 is correlated with the metastatic potential of human nasopharyngeal carcinoma cells. Therefore, CXCR4 may be considered as a potential target for the prevention of nasopharyngeal carcinoma metastasis.
BACKGROUND & OBJECTIVE: Since three-dimensional culture simulates in vivo microenvironment better than planar culture, the biological character of cells in three-dimensional culture model are more similar with that of living tissues. This study was to establish three-dimensional culture models that represent different stages of nasopharyngeal caicinogenesis, and provide information to elucidate the related molecular events. METHODS: Non-tumor nasopharyngeal biopsy specimens were used to culture for normal nasopharyngeal epithelial cells. Early and late passages of normal nasopharyngeal epithelial cell line NPNE2 from nasopharyngeal biopsy specimens, immortalized nasopharyngeal epithelial cell line NP69SV40T, nasopharyngeal carcinoma (NPC) cell line SUNE-1 and its high metastatic subclone 5-8F were cultured in Matrigel to establish three-dimensional models. RESULTS: The cells grew out of non-tumor nasopharyngeal biopsy specimens displayed the morphologic characteristics as epithelia, and could proliferate in vitro for 8-10 passages before senescence. Immunocytochemical staining of cytokeratin revealed that the cells were of epithelial origin. All of the cells, except late passages of NPNE2 cells, could proliferate in the three-dimensional culture system. NPNE2 and NP69SV40T cells mainly developed reticular structures in morphology, and formed few clones with clear and smooth edges as well as tight intercellular junctions. SUNE-1 and 5-8F cells formed clones with irregular morphology, unclear edge, and loose intercellular junctions. In addition, the clones formed by 5-8F cells also developed a lot of pseudopodia, but developed no reticular structure. Late passages of NPNE2 cells formed no clone and reticular structure in the three-dimensional culture. CONCLUSIONS: Normal nasopharyngeal epithelial cells can be successfully cultured in vitro from naspharyngeal biopsy specimens. The three-dimensional culture models, established with normal nasopharyngeal epithelial cells, immortalized nasopharyngeal epithelial cells, and NPC cells, may represent the different stages of nasopharyngeal carcinogenesis.
BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV) closely relates to nasopharyngeal carcinoma (NPC). Whether EBV is a causative viral agent or a by-stander in the carcinogenesis of NPC needs further study. The latent status of EBV during carcinogenesis of NPC remains unknown nowadays. This study was to explore the infectious status of EBV in NPC, and analyze the correlation of EBV to carcinogenesis of NPC. METHODS: Carcinoma tissues,adjacent tissues, and contralateral normal nasopharyngeal tissues from 47 patients with poorly-differentiated nasopharyngeal squamous cell carcinoma were prepared simultaneously. Nasopharyngeal tissues from 10 healthy subjects were used as control. EBV DNA copies levels in the specimens were tested using real-time quantitative polymerase chain reaction (PCR); localization of EBV was detected by in situ hybridization [digoxigenin-labeled EBV-encoded RNA 1 (EBER-1) probe]. RESULTS: Infectious rate of EBV was 80.0% in nasopharyngeal tissues of healthy subjects (mean EBV DNA copies of 6.7x10(2)/microg DNA), 100% in carcinoma tissues and adjacent tissues of NPC patients, and 72.3% in contralateral normal nasopharyngeal tissues of NPC patients (mean EBV DNA copies of 6.9x10(5)/microg DNA, 1.5x10(5)/microg DNA, and 9.8x10(3)/microg DNA, respectively). There was no significant difference in infectious rate and level of EBV between controlateral normal nasopharyngeal tissues of NPC patients and nasopharyngeal tissues of healthy subjects (P>0.05); infectious level of EBV was significantly higher in carcinoma tissues than in adjacent tissues (P<0.05), and significantly higher in adjacent tissues than in contralateral normal nasopharyngeal tissues of NPC patients (P<0.01). Using in situ hybridization, EBER-1 expression signal was not detected in contralateral normal nasopharyngeal epithelia of NPC patients, weak in atypical hyperplastic cells in adjacent tissues, and strong in carcinoma cells. CONCLUSIONS: EBV latent infection is a common phenomenon in nasopharyngeal tissues of both NPC patients and healthy persons. The enhancement of EBV infection plays an important role during carcinogenesis of NPC.
Hemidesmosome (HD) is a transmembrane complex that mediates attachment of epithelial cells to the basement membrane. Abnormal expression of HD components has been reported in several types of human cancers and is believed to play a role in tumor invasion and metastasis. Using differential gene display, we have identified downregulation of BPAG1 expression in nasopharyngeal carcinoma cells. BPAG1 is a major component of hemidesmosome. In the present study, we have extended our work to investigate the expression pattern of other components in the HD complex, namely, BPAG2, ITGalpha6 and ITGbeta4 in three distinct biological groups of nasopharyngeal epithelial cells: (a) non-malignant nasopharyngeal epithelial cells established from primary culture of nasopharyngeal explants, (b) non-malignant nasopharyngeal epithelial cells immortalized by viral oncogenes, SV40 or HPV16E6E7, and (c) nasopharyngeal carcinoma (NPC) cells. Both non-malignant primary cultured nasopharyngeal epithelial cells and immortalized nasopharyngeal epithelial cell lines expressed all the HD components examined, although the immortalized cells expressed a lower level of HD components compared with the non-malignant nasopharyngeal cells established from primary culture. In contrast, downregulation of HD components is commonly observed in nasopharyngeal carcinoma cells. Loss of HD expression in NPC may be associated with the undifferentiated properties of NPC cells and may have prognostic significance.
Nasopharyngeal malignancy accounts for less than 2 per cent of all head and neck cancers. Serous otitis media (SOM) causing deafness is a recognized indicator of nasopharyngeal obstruction and the possibility of a nasopharyngeal malignancy must be considered in all adults. Examination under anaesthesia (EUA) and biopsy of the nasopharynx is routinely undertaken in many centres to rule out nasopharyngeal malignancy in adults with SOM. The purpose of this 10-year retrospective study was to evaluate the case records of all adult cases of SOM, including their presentation, clinical findings, management and nasopharyngeal biopsy results. Eighty-five patients were included in the study. Fifty-nine presented with unilateral SOM and 26 with bilateral SOM. The primary presenting complaint in all cases was hearing loss. A nasopharyngeal mass was documented in 55 patients (69 per cent). Four nasopharyngeal masses were noted to have irregular or exophytic mucosa on flexible nasendoscopy. All patients underwent a EUA of the ears and a nasopharyngeal biopsy. The four patients with suspicious-looking masses were all found to have malignancies (two squamous cell carcinomas, one B-cell non-Hodgkin lymphoma and one adenocarcinoma). Three of these patients presented with unilateral SOM and one with bilateral SOM. All other patients with masses were found to have benign lymphoid hyperplasia. In total, 4.7 per cent of the adults with conductive hearing loss secondary to SOM were found to have a malignancy on nasopharyngeal biopsy. We would advocate a high index of suspicion of a nasopharyngeal tumour in adults presenting with SOM. If a mass is found in the nasopharynx then it should be biopsied. If no mass is found then it is not necessary to biopsy; however, close follow up, with repeat fibre-optic nasendoscopy, is advised.
OBJECTIVES/ HYPOTHESIS: An important tumor suppressor gene, p53, plays a role in the regulation of cell progression and prevention of carcinogenesis. Mutated p53 is related to cell progression and malignancy. We aimed to evaluate the association between nasopharyngeal carcinoma and p53 polymorphism. STUDY DESIGN: Case control study. METHODS: All individuals were divided into two groups: nasopharyngeal carcinoma (n = 50) and non-nasopharyngeal carcinoma groups (n = 59). Their p53 codon 72 polymorphisms (arginine [Arg] homozygotes, heterozygotes, proline [Pro] homozygotes) were detected by polymerase chain reaction. Associations between nasopharyngeal carcinoma and p53 polymorphism were evaluated. RESULTS: Distributions of various p53 polymorphisms significantly differed between the two groups. We noted a dominant presentation of Pro homozygotes in the nasopharyngeal carcinoma population over that in the non-nasopharyngeal carcinoma population. Proportions of Pro homozygotes and heterozygotes and Arg homozygotes were 32%, 28%, and 40% in the nasopharyngeal carcinoma population and were 13.5%, 44.1%, and 42.4% in the non-nasopharyngeal carcinoma population, respectively. CONCLUSIONS: An association exists between nasopharyngeal carcinoma and p53 codon 72 polymorphism. The p53 Pro homozygotes are to a higher risk of development of nasopharyngeal carcinoma.
BACKGROUND: Juvenile nasopharyngeal angiofibroma is a rare nasopharyngeal tumor that occurs exclusively in adolescent boys. It is a histologically benign but locally persistent growth of stromal and vascular tissue. Although male hormones and some growth factors, such as transforming growth factor beta1 (TGF-beta1), insulin-like growth factor II (IGF-II), and, lately, the proto-oncogene beta-catenin, have been implicated in the histogenesis of the tumor, the biologic signaling pathways that drive this peculiar fibrovascular proliferation are still nuclear. OBJECTIVE: To evaluate immunoexpressions of beta-catenin, c-Kit, p130Cas, TGF-beta3, bone morphogenic protein 4, nerve growth factor (NGF), and the IGF receptor (IGF-1R) in a series of juvenile nasopharyngeal angiofibromas and to compare to that of a group of nasal polyps. DESIGN: A standard immunohistochemical technique was used on paraffin sections of 12 sporadic juvenile nasopharyngeal angiofibromas and 15 nasal polyps with microwave or steam antigen retrieval. Immunoreactivity was analyzed semiquantitatively in stromal cells and endothelial cells of each case. RESULTS: The expressions of beta-catenin (nuclear), c-Kit (cytoplasmic), and NGF (cytoplasmic) were higher and more frequent in stromal cells of juvenile nasopharyngeal angiofibromas than those of nasal polyps. Both juvenile nasopharyngeal angiofibromas and nasal polyps showed similarly frequent and strong immunoreactivity for p130Cas and TGF-beta3 and weak immunoreactivity for bone morphogenic protein 4 in both stromal cells and endothelial cells. No IGF-1R immunoreactivity was detected in any case of either group. CONCLUSIONS: Our results support the role of beta-catenin in juvenile nasopharyngeal angiofibromas and suggest a potential involvement of c-Kit and NGF signaling pathways in the juvenile nasopharyngeal angiofibromas. Although the biologic significance of c-Kit in juvenile nasopharyngeal angiofibromas has yet to be defined, the finding of frequent and high c-Kit expression might have therapeutic importance for patients with juvenile nasopharyngeal angiofibromas.
This review is to summarize the main achievements of studying the biological characteristics of nasopharyngeal carcinogenesis performed by the authors' research team and the recent advancement in this field during the past 5 years as well as to explain the authors' viewpoints concerning the nasopharyngeal carcinogenesis. In order to study the nasopharyngeal carcinogenesis, more than 20,000 nasopharyngeal carcinoma biopsies and more than 600 nasopharyngeal biopsies of Epstein-Barr virus seropositive persons who had been got follow-up over 12 years, were collected. In addition, nude mice and cell lines were also to be utilized. Besides histopathological staining, methods of molecular biology, including in-situ hybridization, PCR etc. were applied. Up to date, 26 papers concerning this subject had been formally published in the medico-biological journals at home and abroad. The results and conclusions were as follows. (1) The squamous metaplasia, epithelial dysplasia, carcinoma in-situ and microinvasive carcinoma are the morphogenetic sequence found in nasopharyngeal carcinogenesis. (2) This morphogenetic sequence is frequently observed in a restricted area of nasopharyngeal mucosal epithelium, representing as an appearance of field carcinogenesis. (3) EB virus may play a critical role in nasopharyngeal carcinogenesis, since EB virus DNA and small RNAs could be detected in epithelial dysplasia first and several viral encoded products, especially LMP1, might be expressed in dysplasia, carcinoma in-situ and microinvasive carcinoma. (4) The multigenic mechanisms, including interactions between EB viral genes encoded products and the products abnormally expressed step by step from genes related to cell-cycle regulation, are the molecular events involved in nasopharyngeal carcinogenesis. (5) The cellular immunity of individuals should also be considered as an important factor influencing nasopharyngeal carcinogenesis, because EB virus specific cytotoxic T-lymphocytes could not only be observed in carcinoma nests but also detected in peripheral blood.
Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC. Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16(INK4A) locus and downregulation of RASSF1A expression. The deletion of the p16(INK4A) locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16(INK4A) locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-kappaB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development.
BACKGROUND: Nonresponsive acute otitis media (NR-AOM) is reported in > 10% of children with AOM treated with antibiotics. Drug-resistant Streptococcus pneumoniae is currently considered the leading cause of antibiotic failures in AOM. Nasopharyngeal colonization with S. pneumoniae was found to increase significantly during episodes of AOM. OBJECTIVES: To investigate the nasopharyngeal colonization with S. pneumoniae during NR-AOM and compare it with that found in AOM not recently treated with antibiotics (NT-AOM); to assess the predictive value of nasopharyngeal pneumococcal cultures results for the bacteriologic assessment of NR-AOM. MATERIALS AND METHODS: Patients age 3 to 48 months with NT-AOM and NR-AOM were prospectively studied. Simultaneous nasopharyngeal cultures for S. pneumoniae and middle ear fluid cultures were obtained at enrollment. Antibiotic susceptibility testing was performed in all S. pneumoniae isolates. Penicillin and ceftriaxone MICs for S. pneumoniae were determined by E-test. The sensitivity, specificity and positive and negative predictive values of positive or negative nasopharyngeal cultures for the presence of S. pneumoniae in middle ear fluid were calculated. RESULTS: We studied 362 and 217 children with NT-AOM and NR-AOM, respectively. Of the children with NT-AOM and NR-AOM, 95 and 97%, respectively, were younger than 2 years of age. S. pneumoniae was isolated in the nasopharynx of 66 and 58% of children with NT-AOM and NR-AOM, respectively. Penicillin-nonsusceptible S. pneumoniae was isolated more frequently from the nasopharynx of patients with NR-AOM than from those with NT-AOM (84% vs. 47%; P < 0.01). Antibiotic susceptibility patterns were similar for S. pneumoniae isolates recovered from the nasopharynx and those from the middle ear fluid in both NT-AOM and NR-AOM. A positive nasopharyngeal culture had only little predictive value for the presence of S. pneumoniae in middle ear fluid (41 and 51% for NT-AOM and NR-AOM, respectively). However, the negative predictive value of nasopharyngeal cultures for recovery of S. pneumoniae in NR-AOM was high and significantly higher in NR-AOM than in NT-AOM (91% vs. 78%, respectively; P = 0.009). The negative predictive value of nasopharyngeal cultures for recovery of antibiotic-resistant S. pneumoniae was 95 and 93% in NT-AOM and NR-AOM, respectively. Conclusions. A significantly higher nasopharyngeal colonization rate with antibiotic-resistant S. pneumoniae was found in patients with NR-AOM than in those with NT-AOM. Negative nasopharyngeal culture for antibiotic-resistant S. pneumoniae practically rules out its presence in middle ear fluid.
Nasopharyngeal carcinoma, a malignancy associated closely with Epstein-Barr virus (EBV), is prevalent among Chinese of Southern China origin. Epidemiological studies indicate a high prevalence of EBV in Asia with viral isolates having typical characteristics of the putative viral oncogene, latent membrane protein 1 (LMP-1), such as the loss of the Xho1 restriction site in Exon 1 and the 30-bp deletion in Exon 3. The EBV LMP-1 gene from throat washings of 120 nasopharyngeal carcinoma patients and 14 healthy individuals were analyzed. Similar analyses were also carried out on 30 and 12 postnasal space biopsies from nasopharyngeal carcinoma patients and healthy individuals, respectively. The 30-bp deletion was detected in 20% of nasopharyngeal carcinoma throat washes and in 100% of nasopharyngeal carcinoma postnasal space biopsies. Interestingly, 16% of the nasopharyngeal carcinoma biopsies possessed both the deleted and the undeleted variants, suggestive of dual infections. The notion of dual infections in nasopharyngeal carcinoma was further supported by the coexistence of both "F" and "f" (BamH1F region) EBV variants in 11% of the nasopharyngeal carcinoma biopsies. All of the throat washes and biopsies from the healthy controls showed the undeleted variant. The loss of the Xho1 restriction site was found with higher frequency both in throat washes and biopsies from patients with nasopharyngeal carcinoma. The discrepancy in the frequency of the 30-bp deletion between throat washes (20%) and postnasal space biopsies (100%) was an indication that this deletion is specific for viral isolates from primary tumour sites.
Telomeres are specialized structures at the ends of eukaryotic chromosomes which are composed of simple repetitive G-rich hexameric sequences. Activation of telomerase, a ribonucleoprotein that synthesizes telomeric DNA, is found in most malignant tumors. However, little data is available concerning the correlation between telomerase activity and NPC (nasopharyngeal carcinoma). In this study, telomerase activation was determined using the TRAP (telomerase repeat amplification protocol) assay in 62 nasopharyngeal biopsies (25 NPC, 25 non-malignant nasopharyngeal lymphoid tissues, 12 post-irradiated nasopharyngeal tissues). The results showed that strong telomerase activity was present in both NPC and non-malignant nasopharyngeal biopsies. Post-irradiated nasopharyngeal samples had a significantly lower telomerase activity than NPC and non-malignant nasopharyngeal lymphoid tissues. It is well known that nasopharyngeal tissue is infiltrated by numerous lymphocytes, which might retain telomerase activity. Therefore, the finding that the telomerase activation was lowest in post-irradiated nasopharyngeal tissues is reasonable because of the destruction of activated lymphocytes and NPC by radiation. NPC biopsies with positive lymph node involvement exhibited higher levels of telomerase compared to those without lymph node involvement. Our data indicate a positive association between telomerase activity and tumor potential for lymphatic spreading in limited local tumors. In addition, telomerase activity may be useful as a diagnostic marker in the detection of tumor cells in recurrent NPC, but not in primary NPC.
OBJECTIVE: To investigate the expression of tumor suppressor gene PTEN in nasopharyngeal carcinomas and the relationship between PTEN and the progression of nasopharyngeal cancer. METHOD: The SABC immunohistochemistry method was employed to detect the expression of PTEN in paraffin-embedded nasopharyngeal carcinoma tissues. The relationship between the geneexpression and clinicopathological features was analyzed. RESULT: Loss of PTEN expression in normal cases (13.3%) was lower than that in nasopharyngeal carcinoma cases (47.8%). Of nasopharyngeal cancer cases, loss of PTEN expression in squama cell nasopharyngeal (58.1%) was higher than that in others tissue type (30.8%); loss of PTEN expression in squama cell nasopharyngeal had correlation with pathological stage, which increased gradually from poorly differentiated to well differentiated squama cell nasopharyngeal; loss of PTEN expression of clinical III-IV stage (78.1%) was higher than that of clinical I-II stage (21.6%). CONCLUSION: It is presumed that PTEN gene deletion may be involved in carcinogenesis and progression of nasopharyngeal carcinoma, and relates to the tissue type, the pathological grade and clinical stage.
OBJECTIVE: To determine the effectiveness of nasopharyngeal cooling for selective brain cooling and neuroprotection from ischemia. DESIGN: Prospective animal study. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Male Wistar rats (n = 28). INTERVENTIONS: In study 1, hippocampal temperature was decreased to 31 degrees C under spontaneous circulation. In the nasopharyngeal cooling group, physiologic saline (5 degrees C) was infused to the bilateral nasal cavities at the rate of 100 mL.min-1.kg weight-1. In the whole body cooling group, a fan and a water blanket (5 degrees C) were used. In study 2, ischemia and resuscitation were performed in normothermic and nasopharyngeal cooling (initiated with resuscitation after 5 mins of ischemia and continued for 20 mins) groups. MEASUREMENTS AND MAIN RESULTS: The hippocampal temperature was decreased to 31 degrees C in 7 +/- 2 mins without any change in the rectal temperature in the nasopharyngeal cooling group, whereas a decrease in hippocampal temperature to 31 degrees C took 33 +/- 1 mins in the whole body cooling group. Although skull base region was cooled by nasopharyngeal cooling, the epidural temperature of the parietal region was lower than the hippocampal temperature, indicating that brain temperature was hematogenously lowered. There was no difference between changes in cerebral blood flow or between the ratios of oxygen extraction from arterial blood in the head region in the nasopharyngeal cooling and whole body cooling groups. In the second study, all animals were successfully resuscitated, and the times required for recovery of mean arterial blood pressure (60 mm Hg) after resuscitation in the nasopharyngeal cooling and normothermic groups were the same. The histologic damage was significantly attenuated in the nasopharyngeal cooling group (33 +/- 21% cell death in the hippocampus) compared with that in the normothermic group (73 +/- 11%). CONCLUSIONS: Nasopharyngeal cooling enables rapid and selective reductions in cortical and subcortical temperatures without disturbing the recovery of systemic circulation after resuscitation.