Cytochrome b5 reductase 2 suppresses tumor formation in nasopharyngeal carcinoma by attenuating angiogenesis / 癌症

<p><b>BACKGROUND</b>Cytochrome b5 reductase 2 (CYB5R2) is a potential tumor suppressor that inhibits cell proliferation and motility in nasopharyngeal carcinoma (NPC). Inactivation of CYB5R2 is associated with lymph node metastasis in NPC. This study aimed to explore the mechanisms contributing to the anti-neoplastic effects of CYB5R2.</p><p><b>METHODS</b>Polymerase chain reaction (PCR) assays were used to analyze the transcription of 84 genes known to be involved in representative cancer pathways in the NPC cell line HONE1. NPC cell lines CNE2 and HONE1 were transiently transfected with CYB5R2, and data was validated by real-time PCR. A chick chorioallantoic membrane (CAM) embryo model was implanted with CYB5R2-expressing CNE2 and HONE1 cells to evaluate the effect of CYB5R2 on angiogenesis. An immunohistochemical assay of the CAM model was used to analyze the protein expression of vascular endothelial growth factor (VEGF).</p><p><b>RESULTS</b>In CYB5R2-transfected NPC cells, PCR assays revealed up-regulated mRNA levels of Fas cell surface death receptor (FAS), FBJ murine osteosarcoma viral oncogene homolog (FOS), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), integrin beta 3 (ITGB3), metastasis suppressor 1 (MTSS1), interferon beta 1 (IFNB1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) and down-regulated levels of integrin beta 5 (ITGB5), insulin-like growth factor 1 (IGF1), TEK tyrosine kinase (TEK), transforming growth factor beta receptor 1 (TGFBR1), and VEGF. The angiogenesis in the CAM model implanted with CYB5R2-transfected NPC cells was inhibited. Down-regulation of VEGF by CYB5R2 in NPC cells was confirmed by immunohistochemical staining in the CAM model.</p><p><b>CONCLUSION</b>CYB5R2 up-regulates the expression of genes that negatively modulate angiogenesis in NPC cells and down-regulates the expression of VEGF to reduce angiogenesis, thereby suppressing tumor formation.</p>

Aberrant promoter hypermethylation of CHFR in nasopharyngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To discover the relationship of transcriptional levels and promoter methylation status of CHFR gene in human nasopharyngeal carcinoma,to discuss the significance and epigenetic mechanism of CHFR inactivation in NPC, and to evaluate the feasibility of detecting methylated CHFR in nasopharyngeal swab as a means for diagnosis of NPC.@*METHOD@#Transcriptional levels of CHFR was evaluated by RT-PCR. Methylation specific PCR was used to detect the methylation status of CHFR in NPC cells, normal nasopharyngeal epithelia, primary tumors and their paired nasopharyngeal swabs. Detailed methylation status was confirmed by bisulfite sequencing. NPC cells were treated by the methyltransferase inhibitor 5-aza-dC and the reactivation of CHFR was evaluated by RT-PCR.@*RESULT@#CHFR transcription was inactivated in NPC. The methylation frequency in NPC primary tumors and their paired swabs were 65.5% and 63.8%, respectively, with a 86.2% concordance. Bisulfite sequencing revealed a dense methylation in NPC cells and primary tumors, but all the normal nasopharyngeal epithelia were unmethylated. CHFR expression were restored after 5-aza-dC treatment.@*CONCLUSION@#CHFR is epigenetically inactivated by promoter methylation in NPC. Detecting methylated CHFR can be served as a useful non-invasive means for diagnosis of NPC.

Expression and significance of tyrosine kinase receptors B in nasopharyngeal carcinoma patients / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#This study was to explore the expression and clinicopathologic features of Tyrosine kinase receptors B (TrkB) and its ligand brain-derived neurotrophic factor (BDNF) in nasopharyngeal carcinoma (NPC).@*METHOD@#Immunohistochemistry was adopted to detect the expression level of TrkB and BDNF in NPC patients.@*RESULT@#Both TrkB and BDNF were expressed in NPC as well as in chronic inflammation. The active expression rate of TrkB in NPC was 82.5% (47/57) and BDNF was 52.6% (30/57), both of which were higher than those in chronic inflammation (P 0.05). There were no statistical significance for degrees of BDNF expression in T stage, clinical stage and lymph node metastasis in NPC (P > 0.05). The expression of TrkB was unrelated to the expression of BDNF (r = 0.049, P > 0.05).@*CONCLUSION@#The high expression rate of TrkB and BDNF maybe plays an important role in development of NPC. It is suggested that TrkB and its ligand BDNF may act as an important index for forecasting the development and metastasis of NPC.

The analysis of plasma Urokinase-type plasminogen activator and Urokinase-type plasminogen activator receptor which unknown factor nosebleed patients / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the pathogenesis of unknown nosebleed patients.@*METHOD@#The ELISA test were used to detected plasma Urokinase-type plasminogen activator (uPA) and Urokinase-type plasminogen activator receptor (uPAR) level in 19 cases unknown factor nosebleed patients and 36 health persons.@*RESULT@#The results showed uPAR and uPA level in nosebleed group (before treatment) uPAR (0.14 +/- 0.04) microg/L, uPA (0.24 +/- 0.09) microg/L; (after treatment) uPAR (0.08 +/- 0.02) microg/L, uPA (0.18 +/- 0.07) microg/L. And normal group uPAR (0.07 +/- 0.03) microg/L, uPA (0.17 +/- 0.05) microg/L. The uPAR and uPA level in nosebleed group before treatment is higher than that in normal group (P 0.05).@*CONCLUSION@#The reasons of uPAR and uPA level high in unknown factor nosebleed patients were not clear, maybe relation to vascular endothelial cell, smooth muscle cell and neutrophil-monocytic release more uPAR and uPA. So uPAR and uPA density of nostril accumulation is more high in its microenvironment, that fibrinolytic system activated increase and result in its hyperactivity, and happened nosebleed when blood be in hypocoagulable state.

Effects on distant metastasis of misdiagnosis of nasopharyngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the effects of situation of misdiagnosis of nasopharyngeal carcinoma (NPC) on distant metastasis.@*METHOD@#The history of diagnosis and treatment of 85 newly diagnosed cases with nasopharyngeal carcinoma were studied by using itemized questionnaire purposely; 433 patients with different prognosis were analyzed retrospectively for the misdiagnoses and mistreatment, including surgical biopsy in the neck.@*RESULT@#(1) The rate of misdiagnosis of 85 patients was 72.64%, and the percentage decreased as the level of the hospitals increased; the majority of the patients (77.36%) were diagnoses within 1 month after the first symptom had appeared; the number of diseases misdiagnosed was 20, most common of which were lymphnoditis, tuberculosis of lymph node and secretory tympanitis; (2) Our data showed that among 433 patients analysed retrospectively, 60 cases had undergone surgical biopsy in the neck, 75% of whom had never received nasopharyngeal biopsy; 43 cases had underwent nasopharyngeal biopsy after the pathological diagnosis as metastatic carcinoma of neck biopsy (71.67%) and the rest (20.0%) received radiotherapy directly or after negative nasopharyngeal biopsy for merely 1 to 4 times; of those 43 cases who were diagnosed as NPC by nasopharyngeal biopsy, 79.17% got positive results at first sampling. (3) Rate of misdiagnosis and mistreatment including surgical biopsy in the neck of patients who had been tumor-free for 5 years or above was significantly lower than that of those who experienced distant metastasis after or before treatment (P < 0.05).@*CONCLUSIONS@#Misdiagnosis and mistreatment including biopsy by surgery of neck is common even in high-grade hospitals; it is doctor that is responsible for this situation; the high occurrence rate of misdiagnosis and mistreatment, biopsy by neck surgery, especially the delayed treatment after the neck biopsy are the factors that contribute to distant metastasis of NPC.

Correlation between expression of TIAM1 gene and carcinomas of larynx / 临床检验杂志

Objective To study the relation between Tiam1 gene(T lymphoma invasion/metastasis 1)and carcinomas of larynx metastasized to lymph node.Method Using reverse transcription polymerase chain (RT-PCR) mRNA overexpression of Tiam1 gene in 30 cases of carcinoma of larynx tissue,12 lymph nodes and 10 cases of normal larynx tissue was studied.Result The frequency of TIAM1 overexpression was 75% (6/8) in primary carcinomas of larynx with metastasis but only 18.7%(4/22) in those without metastasis(P=0.0072).Overexpression of TIAM1 in metastasized lymph nodes was observed in 100% (8/8) of lymph nodes with metastasis but in only 25%(1/4) of the lymph nodes without metastasis of carcinoma(P=0.0182).The frequency of TIAM1 overexpression was 33.3% (10/30) in primary carcinomas of larynx.Conclusion Our data suggest that the overexpression of the TIAM1 gene correlates with lymph node metastasis of carcinomas of larynx.

Following-up study on radiation-induced retinopathy in nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To investigate the frequency of ocular complication and the quality of patient's life after radiation therapy in nasopharyngeal carcinoma ( NPC ) . Methods 254 NPC patients who initially received radiation were followed and analysed. Visual acuity, automational visual field, slit-lamp microscopic findings, pattern visual evoked potential ( P-VEP ) and fundal findings were determined before, during and after radiation therapy. The severity of retinal impairment was assessed according to the international criteria on late tissue effects. Results The radiation dose was more than 70 Gy in 241 (94.9%)NPC patients, giving a radiation retinopathy incidence of 8. 7 % (22) patients after a mean of 46. 8 ? 14. 4 months. After being diagnosed as radiation retinopathy, 16 patients received combined-modality therapy of the modern medicine and Chinese traditional medicine. The disease condition was controlled in 56% (9) patients but progressed into optic neuropathy in 7 patients, 3 of whom developed radiation encephalopathy in 14 to 20 months after onset of retinopathy. The morbidity of radiation retinopathy was not associated with the patient' s age, but was related to the radiation dose. The retinopathy rate was as high as 13.6% in the 75-79 Gy group, which is significantly higher than 5.6% in the 70-74 Gy group ( P