ABSTRACT
Objective:To investigate the influence of endoplasmic reticulum stress (ERS) in the degeneration of cochlear hair cells in the type 2diabetic mice, and to clarify its mechanism.Methods:Twenty clean Kun Ming male mice aged one month were selected and randomly divided into control group and model group (n=10) .The mice in model group were injected with STZ (40 mg·kg-1) to establish the type 2diabetic models.The fasting blood glucose levels of the mice were measured through collecting the vena caudalis blood of the mice.Auditory brain stem response (ABR) was used to detect the ABR threshold of the mice.Otoacoustic emission (OAE) test was used to detect the OAE threshold of mice.The defect rate of mouse cochlear outer hair cells was calculated by the mouse cochlear spreading technique.The expression levels of GRP78, caspase-12, p-ERK and Nrf2proteins were detected by Western blotting method.Results:Compared with control group, the fasting blood glucose levels of the mice in model group at the 7th and the 14th days had no significant differences (P＞0.05) , but the levels were increased significantly at the 21th, 28th and 35th days and the level reached the highest value at the 35th day.The ABR thresholds of the mice in model group at 8, 12, and 24kHZ were increased significantly compared with control group (P＜0.05) .Under the stimulation of low frequency, there was no significant change in the OAE threshold of the mice in model grouop compared with control group.The OAE thresholds of the mice in model group were increased significantly under the medium frequency and high frequency stimulation compared with control group (P＜0.05) .The defects of the cochlear hair cells were mainly concentrated on the bottom of gyrus of the mice, and the defects in middle temporal gyrus and parietal gyrus were less.Compared with control group, the defect rate in the bottom of gyrus of the mice in model group was increased significantly (P＜0.05) ;the defect rates in the middle temporal gyrus and parietal gyrus were increased, but there was no significant difference (P＞0.05) .The expression levels of p-ERK and Nrf2in the cochlear hair cells of the mice in model group were lower than those in control group (P＜0.05) , and the expression levels of GRP78and caspase-12were higher than those in control group (P＜0.05) .Conclusion:ERS can result in the increase of defect rate of cochlear outer hair cells and ABR brainstem hearing threshold of the diabetic mice and decrease the expression levels of p-ERK and Nrf2proteins, suggesting that ERS can promote the degenerative lesions of cochlear hair cells in the type 2diabetic mice.
ABSTRACT
OBJECTIVE@#To investigate the role of Keap1-Nrf2-ARE pathway in laryngeal carcinoma occurrence and development.@*METHOD@#Thirty-five laryngeal carcinoma samples and para-carcinoma tissues were taken from the patients who accepted operation treatment in our hospital from Feb 2012 to Sep 2013. The expression levels of Nrf2 and Keap1 were detected in 35 cases of laryngeal carcinoma with SP immunohistochemical methods. The data were analyzed by the SPSS 13.0 statistical software.@*RESULT@#The expression of Nrf2 in the 35 cases of laryngeal carcinoma was 77.14%, which in the para-carcinoma tissues was 8.57%, the difference between these two groups was statistically significant (P 0.05).@*CONCLUSION@#Keap1-Nrf2-ARE pathway may play an important role in progression of laryngeal squamous cell carcinoma.
Subject(s)
Humans , Biomarkers, Tumor , Metabolism , Carcinoma, Squamous Cell , Metabolism , Head and Neck Neoplasms , Metabolism , Intracellular Signaling Peptides and Proteins , Metabolism , Kelch-Like ECH-Associated Protein 1 , Laryngeal Neoplasms , Metabolism , Lymphatic Metastasis , NF-E2-Related Factor 2 , Metabolism , Neoplasm Staging , Squamous Cell Carcinoma of Head and NeckABSTRACT
OBJECTIVE@#The purpose of this study was to investigate the expression of PKM2 and HIF-1α in laryngeal squamous cell carcinoma and to analyze their correlation in laryngeal squamous cell carcinoma.@*METHOD@#Total 37 laryngeal carcinoma samples and para-carcinoma tissues were taken from the patients who accepted operation treatment in the Second Hospital of HeBei Medical University from 06/2013 to 06/2014. The protein expression levels of PKM2 and HIF-1α were detected with SP immunohistochemical methods. The data were analyzed by the SPSS 13.0 statistical software.@*RESULT@#The positive expression of PKM2 in laryngeal carcinoma tissues and adjacent tissues were 62.16% and 13.15%. The difference was statistically significant (P 0.05). The expression of PKM2 was positively related with HIF-1α in laryngeal squamous cell carcinoma (P < 0.01).@*CONCLUSION@#The expression of PKM2 and HIF-1α are related with the proliferation, invasion and metastasis of laryngeal squamous cell carcinoma. It provides a certain theoretical basis for laryngeal cancer diagnosis and screening to measure the expression of PKM2 and HIF-1α as biological indicators.
Subject(s)
Humans , Biomarkers, Tumor , Metabolism , Carcinoma, Squamous Cell , Metabolism , Carrier Proteins , Metabolism , Head and Neck Neoplasms , Metabolism , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Laryngeal Neoplasms , Metabolism , Lymphatic Metastasis , Membrane Proteins , Metabolism , Squamous Cell Carcinoma of Head and Neck , Thyroid Hormones , MetabolismABSTRACT
OBJECTIVE@#To investigate the functional mechanism of metadherin (MTDH), hypoxia-inducible factor-1 alpha (HIF-1α) and transketolase-like gene 1 (TKTL1) and their interaction with each other in laryngeal carcinoma development.@*METHOD@#Thirty laryngeal carcinoma samples and 20 samples of para-carcinoma tissue were taken from the patients received operation treatment. The expression levels of MTDH, HIF-1α and TKTL1 were detected in all the samples by SP immunohistochemical methods. The data were analyzed by the SPSS13.0 statistical software.@*RESULT@#The positive expression rate of MTDH, HIF-1α and TKTL1 in the 30 cases of laryngeal carcinoma was 56.67%, 60.00% and 63.33%, respectively, which was 20.00%,10.00% and 15.00% respectively in the para-carcinoma tissue, the difference of the positive expression rate of the tested objects between these two groups was statistically significant (P 0.05). The Spearman's rank correlation analysis showed that the positive expression rates of MTDH and HIF-1α in laryngeal carcinoma had positive correlation (r = 0.384, P 0.05).@*CONCLUSION@#It suggested that these three proteins may have close relationship with the occurrence, invasion and metastasis of the laryngeal carcinoma. MTDH and TKTL1 may be expected to be new clinical targets for laryngeal carcinoma treatment and it could offer theoretical basis for the prognosis of the laryngeal carcinoma.
Subject(s)
Humans , Carcinoma, Squamous Cell , Diagnosis , Metabolism , Cell Adhesion Molecules , Metabolism , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Laryngeal Neoplasms , Diagnosis , Metabolism , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Transketolase , MetabolismABSTRACT
OBJECTIVE@#To explore the expression of phospholipase Cgamma-2 (PLCgamma-2), lipoxygenase-12 (12-LOX) and arachidonic acid (AA) in laryngeal squamous cell carcinoma and to study the the relationship between lipid metabolism and laryngeal squamous cell carcinoma.@*METHOD@#In 30 cases of carcinoma tissue and peritumoral laryngeal mucosa tissues (confirmed to be normal laryngeal tissues by pathology), immunohistochemical method (Streptavidin-peroxidase method, SP method) was used for the detection of expression of PLCgamma-2 and 12-LOX, and gas chromatography/mass spectrometry (GC/MS) for the content of the arachidonic acid in carcinoma tissue and peritumoral normal laryngeal mucosa tissues.@*RESULT@#The positive rates of PLCgamma-2 and 12-LOX in carcinoma tissue were higher than in peritumoral normal laryngeal mucosa tissues with statistically significance differences (P 0.05). Both the expression of PLCgamma-2 and 12-LOX and the content of arachidonic acid had no statistically significant correlation with age (P > 0.05).@*CONCLUSION@#PLCgamma-2, AA and 12-LOX play important roles in laryngeal squamous cell carcinoma. It may be meaningful to the treatment of laryngeal carcinoma by suppressing this passway.
Subject(s)
Aged , Humans , Male , Middle Aged , Arachidonate 12-Lipoxygenase , Metabolism , Arachidonic Acid , Metabolism , Carcinoma, Squamous Cell , Metabolism , Pathology , Head and Neck Neoplasms , Metabolism , Pathology , Laryngeal Neoplasms , Metabolism , Pathology , Neoplasm Staging , Phospholipase C gamma , Metabolism , Squamous Cell Carcinoma of Head and NeckABSTRACT
OBJECTIVE@#To explore the expression and significance of survivin and proliferating cell nuclear antigen (PCNA) on the occurrence, proliferation, recurrence and carcinogenesis of the sinonasal inverted papilloma (SNIP).@*METHOD@#Immunohistochemical method was used to detect the expression of survivin and PCNA in 10 cases of nasal cavity mucosal (NM), 45 cases of SNIP and 9 cases of canceration SNIP.@*RESULT@#The positive expression of survivin and PCNA increased gradually in NM,SNIP and canceration PCNA group, and there were significant difference between the three groups. But there was no correlation between survivin and PCNA in the tissue of SNIP (r = 0.135, P > 0.05).@*CONCLUSION@#Survivin and PCNA are involved in the growth and carcinogenesis of SNIP.
Subject(s)
Humans , Inhibitor of Apoptosis Proteins , Metabolism , Nose Neoplasms , Metabolism , Pathology , Papilloma, Inverted , Metabolism , Pathology , Paranasal Sinus Neoplasms , Metabolism , Pathology , Proliferating Cell Nuclear Antigen , Metabolism , Repressor Proteins , Metabolism , SurvivinABSTRACT
OBJECTIVE@#To explore the expression of Smac(second mitochondria-derived activator of caspase)and survivin on the growth, development, recurrence and carcinogenesis of the sinonasal inverted papilloma(NIP).@*METHOD@#Immunohistochemical method was used to detective the expression of Smac and survivin in 10 cases of (nasal cavity mucosae, NM), 45 cases of NIP. The NIP group including 25 cases of NIP without dysplasia, 11 cases of NIP with dysplasia, and 9 cases of NIP with malignant transformation to squamous cell carcinoma(SCC).@*RESULT@#The intensity of the positive expression of Smac in NIP was lower than NM, the intensity of the positive expression decreased with the decreasing degree of histological differentiation. There was significantly difference between NIP without dysplasia and SCC. The expression of survivin was negative in the control group, the expression intensity of NIP was enhanced. The degree of histological differentiation was lower, the intensity of the positive expression was higher. The expression between NIP without dysplasia and SCC had significantly differences. Smac negatively correlated with survivin(rs = -0.403, P<0.01).@*CONCLUSION@#Smac and survivin were associated with the growth and carcinogenesis of NIP.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Inhibitor of Apoptosis Proteins , Metabolism , Intracellular Signaling Peptides and Proteins , Metabolism , Mitochondrial Proteins , Metabolism , Nasal Mucosa , Metabolism , Pathology , Nose Neoplasms , Metabolism , Pathology , Papilloma, Inverted , Metabolism , Pathology , SurvivinABSTRACT
OBJECTIVE@#To explore the expression and significance of second mitochondria derived activator of caspase (Smac), X-linked inhibitor of apoptosis protein (XIAP)and cysteine containing aspartate specific protease 3 (caspase-3) in the growth, development and carcinogenesis of the nonnasal inverted papilloma (NIP).@*METHOD@#Immunohistochemical method was used to detect the expression of Smac, XIAP, caspase-3 in 10 cases of nasal cavity mucosae (NM) and 45 cases of NIP, the group of NIP including 25 cases of NIP without dysplasia, 11 cases of NIP with dysplasia, and 9 cases of NIP with malignant transformation to squamous cell carcinoma (SCC).@*RESULT@#The intensity of the positive expression of Smac, Caspase-3 in NIP were lower than NM, the intensity of the positive expression decreased with the decreasing degree of histological differentiation. There was a significant difference between NIP without dysplasia and SCC. It was presented with a progressive tendency for the expression of XIAP in the group of NM and NIP. The lower degree of histological differentiation, the higher intensity of the positive expression. The expression between NIP without dysplasia and SCC had a significant difference. Smac negatively correlated with XIAP (r(s) = -0.323, P < 0.05), XIAP negatively correlated with caspase-3 (r(s) = -0.408, P < 0.01), Smac positively correlated with caspase 3 (r(s) = 0.424, P < 0.01).@*CONCLUSION@#Smac, XIAP, caspase 3 might be associated with the growth and carcinogenesis of NIP.