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Title: Identification of acid-sensing ion channels in adenoid cystic carcinomas

Abstract

Tissue acidosis is an important feature of tumor. The response of adenoid cystic carcinoma (ACC) cells to acidic solution was studied using whole-cell patch-clamp recording in the current study. An inward, amiloride-sensitive Na{sup +} current was identified in cultured ACC-2 cells while not in normal human salivary gland epithelial cells. Electrophysiological and pharmacological properties of the currents suggest that heteromeric acid-sensing ion channels (ASICs) containing 2a and 3 may be responsible for the proton-induced currents in the majority of ACC-2 cells. Consistent with it, analyses of RT-PCR and Western blotting demonstrated the presences of ASIC2a and 3 in ACC-2 cells. Furthermore, we observed the enhanced expression of ASIC2a and 3 in the sample of ACC tissues. These results indicate that the functional expression of ASICs is characteristic feature of ACC cells.

Authors:
 [1];  [2];  [3];  [2];  [4];  [1];  [5];  [6]
  1. Department of Oral and Maxillofacial Surgery, School of Stomatology, Affiliated Ninth People's Hospital, Shanghai Jiaotong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China)
  2. (China)
  3. Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)
  4. Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Research Institute of Stomatology, Nanjing 210029 (China)
  5. Department of Oral and Maxillofacial Surgery, School of Stomatology, Affiliated Ninth People's Hospital, Shanghai Jiaotong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China). E-mail: yjh98001@sjtu.edu.cn
  6. Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China). E-mail: tlxu@ion.ac.cn
Publication Date:
OSTI Identifier:
20979888
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 355; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.02.061; PII: S0006-291X(07)00342-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; CYSTS; POLYMERASE CHAIN REACTION; SALIVARY GLANDS; SODIUM IONS

Citation Formats

Ye Jinhai, Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Research Institute of Stomatology, Nanjing 210029, Gao Jun, Model Animal Research Center and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210061, Wu Yunong, Hu Yongjie, Zhang Chenping, and Xu Tianle. Identification of acid-sensing ion channels in adenoid cystic carcinomas. United States: N. p., 2007. Web.
Ye Jinhai, Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Research Institute of Stomatology, Nanjing 210029, Gao Jun, Model Animal Research Center and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210061, Wu Yunong, Hu Yongjie, Zhang Chenping, & Xu Tianle. Identification of acid-sensing ion channels in adenoid cystic carcinomas. United States.
Ye Jinhai, Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Research Institute of Stomatology, Nanjing 210029, Gao Jun, Model Animal Research Center and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210061, Wu Yunong, Hu Yongjie, Zhang Chenping, and Xu Tianle. Fri . "Identification of acid-sensing ion channels in adenoid cystic carcinomas". United States. doi:.
@article{osti_20979888,
title = {Identification of acid-sensing ion channels in adenoid cystic carcinomas},
author = {Ye Jinhai and Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Research Institute of Stomatology, Nanjing 210029 and Gao Jun and Model Animal Research Center and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210061 and Wu Yunong and Hu Yongjie and Zhang Chenping and Xu Tianle},
abstractNote = {Tissue acidosis is an important feature of tumor. The response of adenoid cystic carcinoma (ACC) cells to acidic solution was studied using whole-cell patch-clamp recording in the current study. An inward, amiloride-sensitive Na{sup +} current was identified in cultured ACC-2 cells while not in normal human salivary gland epithelial cells. Electrophysiological and pharmacological properties of the currents suggest that heteromeric acid-sensing ion channels (ASICs) containing 2a and 3 may be responsible for the proton-induced currents in the majority of ACC-2 cells. Consistent with it, analyses of RT-PCR and Western blotting demonstrated the presences of ASIC2a and 3 in ACC-2 cells. Furthermore, we observed the enhanced expression of ASIC2a and 3 in the sample of ACC tissues. These results indicate that the functional expression of ASICs is characteristic feature of ACC cells.},
doi = {},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 355,
place = {United States},
year = {Fri Apr 20 00:00:00 EDT 2007},
month = {Fri Apr 20 00:00:00 EDT 2007}
}
  • In 1978, Pratt challenged the otolaryngology community to identify an incidence of malignancy in individuals who have previously received radium therapy to the nasopharyngeal lymphoid tissues. This case report is a direct response to that quest and presents a well documented adenoid cystic carcinoma evolving 23 years after radium applicator treatment to the fossa of Rosenmuller. Although a cause-and-effect relationship cannot be scientifically proven, the case history raises several important questions concerning the stimulating effects of radiation on the later onset of frank malignancy.
  • Between 1949-1977, 74 patients with adenoid-cystic carcinoma of various head and neck sites were treated by radiation therapy at Memorial Sloan-Kettering Cancer Center. Radiation therapy alone was employed in 49 patients for recurrent, unresectable disease, and in 25 patients it was given as an adjunct to surgical resection. Among the 49 patients treated with radiation therapy alone, tumor regression was seen in 47 (96%). However, 44 of the 47 (93.5%) subsequently relapsed locally. Relapse occurred within 18 months in one-half of the patients and within 5 years in all of them. Of the 25 patients who received adjunctive radiation therapymore » about one-half relapsed locally within five years. There were 9 patients in this group, however, whose field size exceeded 8x8 cm and the dose of radiation also exceeded 4500 rad: 88% of these patients remained relapse-free at 5 years, compared with only 22% of the other 16 whose dose, or field size, or both, were inadequate by comparison. These data suggest that when irradiation is employed for advanced, inoperable adenoid-cystic carcinoma, it offers useful palliation but is rarely, if ever, curative. Postoperative irradiation, on the other hand, might improve the local control and the survival in patients with operable adenoid-cystic carcinoma who are at high risk for relapse, but only if the field size and the dose are adequate.« less
  • Purpose: This study sought to review a single-institution experience with the management of adenoid cystic carcinoma of the head and neck. Methods and Materials: Between 1960 and 2004, 140 patients with adenoid cystic carcinoma of the head and neck were treated with definitive surgery. Ninety patients (64%) received postoperative radiation to a median dose of 64 Gy (range, 54-71 Gy). Distribution of T stage was: 26% T1, 28% T2, 20% T3, and 26% T4. Seventy-eight patients (56%) had microscopically positive margins. Median follow-up was 66 months (range, 7-267 months). Results: The 5- and 10-year rate estimates of local control weremore » 88% and 77%, respectively. A Cox proportional hazards model identified T4 disease (p = 0.0001), perineural invasion (p = 0.008), omission of postoperative radiation (p = 0.007), and major nerve involvement (p = 0.02) as independent predictors of local recurrence. Radiation dose lower than 60 Gy (p = 0.0004), T4 disease (p 0.005), and major nerve involvement (p = 0.02) were predictors of local recurrence among those treated with surgery and postoperative radiation. The 10-year overall survival and distant metastasis-free survival were 64% and 66%, respectively. Conclusion: Combined-modality therapy with surgery followed by radiation to doses in excess of 60 Gy should be considered the standard of care for adenoid cystic carcinoma of the head and neck.« less
  • Purpose: To analyze the recent experience of patients with adenoid cystic carcinoma treated with radiation therapy at Memorial Sloan-Kettering Cancer Center. Methods and Materials: From 1990 to 2004, a total of 59 patients with a diagnosis of primary adenoid cystic carcinoma of the head and neck received radiation therapy at our institution. The subsite distribution was oral cavity, 28% (n = 17); paranasal sinuses, 22% (n = 13); parotid, 14% (n = 8); submandibular, 14% (n = 8); oropharynx, 10% (n = 6); sublingual, 3% (n = 2); nasopharynx, 3% (n = 2); and other, 5% (n = 3). Tmore » Stage distribution was T1, 34% (n = 20); T2, 19% (n = 11); T3, 14% (n = 8); and T4, 34% (n = 20). Twenty-nine percent of patients (n = 17) were treated with intensity-modulated radiation therapy; 25% (n =15), with three-dimensional conformal therapy, and the remainder, with conventional techniques. Ninety percent (n = 53) of patients received treatment including the base of skull. Results: Median follow-up for surviving patients was 5.9 years. Five-year and 10-year rates of local control and distant metastases-free survival were 91%/81% and 81%/49%, respectively. Five-year and 10-year rates of disease-free and overall survival were 76%/40% and 87%/65%, respectively. On univariate analysis, stage T4 (p = 0.004) and gross/clinical nerve involvement (p = 0.002) were associated with decreased progression free survival, whereas stage T4 and lymph node involvement were associated with decreased overall survival (p = 0.046 and p < 0.001, respectively). Conclusions: Radiation therapy in combination with surgery produces excellent rates of local control, although distant metastases account for a high proportion of failures. Routine treatment to the base of skull reduces the significance of histologic perineural invasion, but major nerve involvement remains an adverse prognostic factor.« less