To investigate the effects of Biyan Jiedu Capsules on the proliferation and apoptosis of nasopharyngeal carcinoma cells and their molecular mechanism, nasopharyngeal carcinoma cells CNE1 and CNE2 were used. They were divided into control group(30% blank serum medium), low-(10% drug-containing serum + 20% blank serum medium), medium-(20% drug-containing serum + 10% blank serum medium), and high-(30% drug-containing serum medium) concentration group of Biyan Jiedu Capsules according to in vitro experiment. After 24 h of intervention, the effects of Biyan Jiedu Capsules on the proliferation of CNE1 and CNE2 were detected by CCK-8 assay, clonal formation experiment, and EdU staining. The effect of Biyan Jiedu Capsules on apoptosis of CNE1 and CNE2 was detected by flow cytometry. Western blot was used to detect the effect of Biyan Jiedu Capsules on the expression of X-linked apoptosis inhibitor protein(XIAP), survivin, proliferating cell nuclear antigen(PCNA), and PI3K/Akt pathway-related proteins in CNE1 and CNE2. The results showed that compared with the control group, the survival rate of CNE1 and CNE2 in the medium and high concentration groups of Biyan Jiedu Capsules could be decreased in a concentration-dependent way(P<0.05, P<0.01). At the same time, EdU staining and clonal formation experiments showed that the proliferation of CNE1 and CNE2 was significantly inhibited in the medium and high concentration groups of Biyan Jiedu Capsules(P<0.05, P<0.01). Flow cytometry showed that the apoptosis rate of CNE1 and CNE2 was significantly increased in all concentration groups of Biyan Jiedu Capsules(P<0.01), and the apoptosis rate was concentration-dependent. Western blot showed that the expressions of XIAP, survivin, PCNA, p-PI3K, and p-Akt in all concentration groups of Biyan Jiedu Capsules were significantly down-regulated(P<0.05, P<0.01). In conclusion, Biyan Jiedu Capsules can inhibit the proliferation and induce apoptosis of nasopharyngeal carcinoma cells possibly by down-regulating the PI3K/Akt signaling pathway.
Humans ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Capsules ; Carcinoma/drug therapy*

OBJECTIVE: To explore the ways of quantitative and objective evaluation for analyzing the multiple influence factors on middle ear function in the patients with primarily diagnosed NPC, and to analyze the influence factors of middle ear function in the patients with primarily diagnosed nasopharyngeal carcinoma (NPC). METHOD: Three hundred and twenty cases (320 ears) of primarily diagnosed NPC patients were examinated with electric otoscope, acoustic immittance measurement, pure tone audiometry, nasopharynx and middle ear CT or MRI scanning, eustachian tube function examination, and electronic nasopharyngoscope. A series of quantitative methods, as the influence factors including T stage, clinical stage, location, diffusion type and form of tumor, eustachian tube function, pharynx mouth shape, imaging extension (nasal, skull base, pharyngeal recess, parapharyngeal space, tensor veli palatini muscle, levator veli palatini and so on), were used to evaluate the middle ear function. SPSS 13.0 was used to anlyze the single and multiple factors in statistics. RESULT: T stage, clinical stage, location, diffusion type, and form of tumor, pharynx mouth shape, imaging extension (nasal, skull base, pharyngeal recess, parapharyngeal space, tensor veli palatini muscle, levator veli palatini) were the single influence factors on the function of middle ear in primarily diagnosed NPC patients. The gender, age, pathological types, N staging and M staging of NPC patients primarily diagnosed had no effect on middle ear function. The multple factors analysis showed that T stage, tumor location, the function of eustachian tube, tensor veli palatini muscle invasion, and skull base invasion were independent factor of affecting the middle ear function on primarily diagnosed NPC patients. CONCLUSION In this study, the influence factors of middle ear function with primarily diagnosed NPC were related to T stage, location of tumor, the function of eustachian tube, tensor veli palatini muscle invasion, skull base invasion, otitis media and quantitative criteria. The way of quantitative analysis could be used to evaluate objectively the middle ear function in patients with primarily diagnosed NPC.
Adult ; Aged ; Aged, 80 and over ; Carcinoma ; Ear, Middle ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; diagnosis ; physiopathology ; Young Adult

BACKGROUND AND OBJECTIVERadiation usually results in paranasal sinusitis in patients with nasopharyngeal carcinoma (NPC), which influences patients' quality of life. This study aimed to determine the relationships between dose distribution in the nasal cavity and nasal mucous injury in patients with NPC treated by intensity-modulated radiation therapy (IMRT), and to find the tolerable radiation dose for the nasal mucous.

METHODSSixty-six patients with NPC treated by IMRT between October 2006 and November 2008 were enrolled. The irradiation dose in the nasal cavity was determined by the computer with the IMRT work platform. Mucociliary transport rate (MTR) was detected by modified saccharine test before IMRT, at the end of IMRT, and at 3, 6, and 12 months after IMRT.

RESULTSThe data were available for 129 nasal cavities. The cavities receiving a mean dose below or equal to 37 Gy showed substantial preservation of nasal mucous after IMRT. The MRT decreased to (62.82 ± 38.59)%, (56.78 ± 37.79)%, (64.05 ± 39.37)%, and (71.13 ± 39.55)% of pre-IMRT value at 4 time points after IMRT, with significant differences among the data (P < 0.05). In contrast, when the cavities received a mean dose higher than 37 Gy, no significant differences in MTR among the time points were observed. At 3 months after IMRT, the MTR was the lowest (38.27% of pre-RT value).

CONCLUSIONSA mean radiation dose of ≤ 37 Gy for the nasal cavity is an optimal dose to protect the nasal cavity function.

Adult ; Carcinoma, Squamous Cell ; physiopathology ; radiotherapy ; Female ; Humans ; Male ; Mucociliary Clearance ; radiation effects ; Nasal Cavity ; radiation effects ; Nasopharyngeal Neoplasms ; physiopathology ; radiotherapy ; Quality Control ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated

OBJECTIVE: To investigate the effects of radioactive ray on transmission capability of nose mucociliary. METHOD: Forty-six patients with NPC were selected and saccharin clearance time (SCT) for 7 phases were detected in both pre- and post-radiotherapy respectively. RESULT: Among 46 patients with NPC, the shortest SCT was 247 seconds and the longest 601 seconds in pre-radiotherapy phases; from 4th week of introradiotherapy to 18 months of postradiotherapy, the longest SCT was in 12 months after radiotherapy, which was 903 seconds. There were no significant differences in SCT before radiotherapy and 18 months after radiotherapy. There were significant differences in SCT of preradiotherapy and introdiotherapy, post radiotherapy, after radiotherapy 3 months, 6 months, 12 months after radiotherapy. CONCLUSION Radiotherapy is the important factors in influencing transmission capability of nose cavity and sinus mucociliary and hints that gender and nasal cavity side don't affect SCT. Detection of SCT in different stages of NPC patients can be helpful to protect nasal mucous membrane effectively, and to reduce incidence rate of RNS.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Mucociliary Clearance ; radiation effects ; Nasal Mucosa ; physiopathology ; Nasopharyngeal Neoplasms ; physiopathology ; radiotherapy ; Saccharin ; metabolism ; Young Adult

OBJECTIVETo investigate the Epstein-Barr virus (EBV) BamH I "f" variant in primary nasopharyngeal carcinoma (NPC) and its metastases in lymph nodes (LN).

METHODSIn situ hybridization was used to detect EBV-encoded small RNA (EBER) expression in 21 paired paraffin-embedded tissue from primary NPC and their lymph node metastases and 22 primary NPC without lymph node metastasis. PCR and restriction fragment length polymorphism (RFLP) assay were used to detect EBV BamH I "f" variant in all cases of NPCs, lymph node metastases and 50 cases of chronic inflammation of nasopharynx from Canton.

RESULTSAll cases of NPCs and their lymph node metastases showed EBER expression, indicating a high EBV-positive rate in Cantonese NPC patients. EBV BamH I "f" variant was found in 11 cases (52.4%, 11/21) of primary NPCs with LN metastasis, 12 cases (57.1%, 12/21) of the LN metastases, and 18 cases (81.8%, 18/22) of primary NPCs without LN metastasis. However, of the 50 cases of chronic inflammation of nasopharynx, only one case (2.1%, 1/47) demonstrated BamH I "f" variant. The frequency of BamH I "f" variant in NPC was therefore dramatically higher than that in chronic inflammation of nasopharynx. It is of note that atypical hyperplasia was observed in a few epithelial cells from the case of chronic inflammation of nasopharynx expressing BamH I "f" variant.

CONCLUSIONSThe frequency of EBV BamH I "f" variant in NPC is significantly higher than that in chronic inflammation of nasopharynx. It is the first demonstration that the BamH I "f" variant is also present in the LN metastases of NPC. The frequency of BamH I "f" variant in metastatic NPC of the lymph node is almost equal to that of primary NPCs.

Epithelial Cells ; drug effects ; Epstein-Barr Virus Infections ; classification ; complications ; virology ; Herpesvirus 4, Human ; classification ; genetics ; Humans ; In Situ Hybridization ; Lymph Nodes ; drug effects ; pathology ; virology ; Lymphatic Metastasis ; physiopathology ; Nasopharyngeal Neoplasms ; genetics ; pathology ; virology ; Nasopharynx ; virology ; RNA, Viral ; analysis ; pharmacology

It is well known that the Epstein-Barr virus (EBV) contributes directly to tumourigenesis in nasopharyngeal carcinoma (NPC), primarily in the undifferentiated form of NPC (WHO type III; UNPC or UC), which is commonly found in South East Asia. Unfortunately, research in NPC has been severely hampered by the lack of authentic EBV-positive (EBV+) human NPC cell lines for study. Since 1975, there have been more than 20 reported NPC cell lines. However, many of these NPC-derived cell lines do not express EBV transcripts in long-term culture, and therefore that finding may dispute the fundamental theory of NPC carcinogenesis. In fact, currently only one EBV+ human NPC cell line (C-666) in long-term culture has been reported. Hence, most of the NPC cell lines may not be representative of the disease itself. In order to better understand and treat NPC, there is an urgent need to develop more EBV+ human NPC cell lines. In this review, we discuss the authenticity of existing NPC cell lines and the impact of our understanding of NPC biology on the treatment of the disease and the relationship of EBV to NPC in the context of cell lines.
Cell Line, Tumor ; virology ; Herpesvirus 4, Human ; pathogenicity ; Humans ; Nasopharyngeal Neoplasms ; physiopathology ; virology

OBJECTIVE: To determine the effect of radiotherapy on the thyroid of patients with nasopharyngeal cancer. METHODS: Thyroid dynamic imaging was performed on 51 patients with nasopharyngeal cancer who had the metastasis of the jugular lymph node before and after the radiotherapy. The peak time of the thyroid artery perfusion and the constant K were obtained. The levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in the blood serum were measured at the same time. RESULTS: The peak time of the left and right thyroid artery perfusion before the radiotherapy was (14.5+/-2.1)s and (15.1+/-1.9)s, respectively, while that after the radiotherapy was (19.3+/-3.2)s and (20.2+/-3.5)s, respectively. There was significant difference between the pre- and post-radiotherapy (P<0.001). The constant K of the left and right thyroid before the radiotherapy was significantly higher than that after the radiotherapy (0.0265+/-0.0074 vs. 0.0173+/-0.0062; 0.0249+/-0.0065 vs. 0.0167+/-0.0053, P<0.001, respectively). The level of FT3 and FT4 was significantly higher than that after the radiotherapy, but the TSH level had no obvious change[(4.76+/-0.95) pmol/L vs. (3.85+/-0.71) pmol/L,P<0.001; (18.63+/-3.84) pmol/L vs. (15.69+/-3.27) pmol/L,P<0.001; (1.17+/-0.52) mU/L vs. (1.22+/-0.76)mU/L ,P>0.05, respectively]. CONCLUSION The peak time of the thyroid artery perfusion and the constant K which reflect blood stream status after the radiotherapy are all damaged in patients with nasopharyngeal cancer. The level of FT3 and FT4 in the blood serum is dropped but the TSH level has no obvious change.
Adult ; Aged ; Female ; Humans ; Hypothyroidism ; blood ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; physiopathology ; radiotherapy ; Thyroid Function Tests ; Thyroid Gland ; radiation effects ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood ; Young Adult

Adult ; Female ; Humans ; Male ; Middle Aged ; Mucociliary Clearance ; Nasal Mucosa ; pathology ; physiopathology ; Nasopharyngeal Neoplasms ; pathology ; physiopathology ; radiotherapy

OBJECTIVETo evaluate the radiation induced parotid dysfunction in nasopharyngeal carcinoma (NPC) patients who had received different methods of radiotherapy.

METHODSFrom January 1996 to January 2000, 380 NPC patients were divided into conventional fraction (CF-175 patients), late-course accelerated hyperfractionation (LCAF-63 patients) and intensity modulated radiation therapy (IMRT-142 patients) groups. Conventional radiotherapy was given with a total dose of 70 Gy. Patients in the LCAF group were treated with the same fractionation as CF group until the dose of 36 - 40 Gy, then followed by LCAF radiotherapy to a total dose of 75 Gy. IMRT in the form of full-course was given to a total dose of 72 Gy. Acute parotiditis was observed during the treatment. The parotid secretory function was examined 2 years after radiotherapy.

RESULTSThe dose of parotid in IMRT was much lower than those in the other 2 groups. Extreme damage rates of parotid secretory function in CF, LCAF and IMRT groups were 81.7%, 81.0% and 69.7% (P < 0.05); acute parotiditis rates were 23.4%, 20.4% and 41.3% respectively, with the differences among the 3 groups significant (P < 0.05).

CONCLUSIONThe radiation parotid functional damage differs in the various methods of radiotherapy. IMRT, being able to improve the tumor target coverage and spare the adjacent critical structures, is indicated for NPC.

Adolescent ; Adult ; Carcinoma, Squamous Cell ; radiotherapy ; Dose Fractionation ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Parotid Gland ; physiopathology ; radiation effects ; Parotitis ; etiology ; Radiation Injuries ; physiopathology ; Radiotherapy, Intensity-Modulated ; methods

BACKGROUNDNasopharyngeal carcinoma (NPC) shows highly invasive and metastatic features. This study aims to investigate macrophage migration inhibitory factor (MIF)-induced invasion of NPC cells in vitro and the effects on matrix metalloproteinases (MMPs) and interleukin-8 (IL-8), and to study the mechanism of tumor cell invasion and metastasis in the early stage of NPC.

METHODSTwo nasopharyngeal carcinoma cell lines, CNE-1 and CNE-2, were adopted in this study. The NPC cell invasion and migration were evaluated by microinvasion assay. The variation of expression percentages of MMP2- or MMP9-positive cells was detected by flow cytometry in two cell lines with or without MIF treatment. Western blotting and RT-PCR were used to assay the protein and mRNA expressions of MMP2 and MMP9. The IL-8 concentration secreted by NPC cells was compared with the cells with different treatments using ELISA.

RESULTSAfter treating with MIF for 48 hours, the cell numbers of CNE-1 and CNE-2 which went through the 8-microm filter membrane were increased. Compared with non-MIF treated NPC cells, significant difference could be found both in CNE-1 (P = 0.005) and CNE-2 cells (P = 0.001). The percentages of MMP9-positive cells were significantly increased in both CNE-1 [from (28.5 +/- 2.5)% to (82.4 +/- 3.5)%, P = 0.001] and CNE-2 [from (32.8 +/- 3.5)% to (86.1 +/- 1.6)%, P = 0.002]. The relative intensity of MMP9 protein expression was also enhanced in both cell lines (CNE-1: from 83.1 +/- 6.0 to 242.9 +/- 22.9, P = 0.002; CNE-2: from 84.4 +/- 4.3 to 278.9 +/- 29.7, P = 0.003). Correspondingly, the increased MMP9 mRNA expression level was significantly detectable in both cell lines. The concentration of IL-8 in the supernatant of CNE-2 was higher [(1201.8 +/- 593.3) pg/ml] after treatment. It was also remarkably higher than that in the supernatant of CNE-2 without treatment (P = 0.026). However, there was no significant difference in the concentration variation of IL-8 in CNE-1 (P = 0.581), while the IL-8 mRNA level was only enhanced in CNE-2.

CONCLUSIONSMIF can induce potent invasion of NPC cell lines in vitro, and the infiltrating lymphocytes in NPC might be responsible for the invasion and metastasis of tumor cells. MIF cytokine which is secreted by these infiltrating lymphocytes might contribute to the invasion as well as metastasis of NPC in the early stages by induction of MMP9 and IL-8 in an indirect pathway.

Blotting, Western ; Cell Line, Tumor ; Electrophoresis, Polyacrylamide Gel ; Humans ; Interleukin-8 ; analysis ; Macrophage Migration-Inhibitory Factors ; pharmacology ; Matrix Metalloproteinase 2 ; analysis ; Matrix Metalloproteinase 9 ; analysis ; Nasopharyngeal Neoplasms ; pathology ; Neoplasm Invasiveness ; physiopathology ; Reverse Transcriptase Polymerase Chain Reaction