Genetic Effects on Sensorineural Hearing Loss and Evidence-based Treatment for Sensorineural Hearing Loss / 中国医学科学杂志(英文版)

In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application.

Novel partners of S100A8 identified in laryngeal cancer cell lines / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore mechanism of S100A8 in the oncogenesis and development of laryngeal cancer.</p><p><b>METHODS</b>Proteins interacting with S100A8 were isolated from laryngeal cancer cell lines Hep-2 by immunoprecipitation assay with anti-S100A8 antibody. The target bands were cut out and identified by maxtrix assisted laser desorption/ionization time of flight (MALDI-TOF). The peptide mass fingerprinting data of the proteins identified were analyzed based on the Mascot database. The NF-kappa B binding sites of the proteins were predicted by P-Match software. The binding ability of one of the proteins to S100A8 was confirmed by co-immunoprecipitation and immunocytochemistry methods.</p><p><b>RESULTS</b>Four proteins interacting with S100A8 were obtained, which were hypothetical protein LOC80154, MHC class I HLA-B, similar to T-box 1 isoform C and sarcolemmal associated protein 1. The four genes were predicted to have NF-kappa B binding sites. MHC class I HLA-B, which is one of targets in NF-kappa B pathway, was first confirmed to have the binding ability to S100A8.</p><p><b>CONCLUSION</b>The novel partners of S100A8 identified in the study might be involved in NF-kappa B pathway. The binding ability of MHC class I HLA-B to S100A8 implies that S100A8 might function as a new member with other proteins including HLA-B in NF-kappa B pathway. These findings provide a new clue to further study on the molecular mechanism of S100A8 in the genesis of laryngeal carcinomas.</p>

Study of the SH3-domain GRB2-like 2 gene expression in laryngeal carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Laryngeal carcinoma is a common malignant tumor of the upper respiratory tract, and in 95% of cases the tumor is laryngeal squamous cell carcinoma (LSCC). The abnormity of SH3-domain GRB2-like 2 (SH3GL2) gene was found in LSCC. In order to clarify the relationship between SH3GL2 gene and LSCC, we evaluated the expression of the SH3GL2 gene in LSCC.</p><p><b>METHOD</b>Real-time PCR, immunohistochemistry and Western blotting were used to detect the mRNA and protein expression and find the various rules of SH3GL2 gene in LSCC.</p><p><b>RESULTS</b>The result of real-time PCR showed that the expression level of SH3GL2 mRNA in LSCC tissue was apparently down-regulated; immunohistochemical analysis showed that SH3GL2 protein was mainly located in cytoplasm, the rate of positive cells and SH3GL2 protein expression level were fluctuated with the pathological classification of LSCC; the result of Western blotting showed that SH3GL2 protein was down-regulated significantly in LSCC samples, especially in metastatic lymph nodes.</p><p><b>CONCLUSIONS</b>These results suggest that SH3GL2 is a LSCC related gene and its expression level is fluctuated with the pathological classification which indicate that SH3GL2 participates in the development and progression of LSCC. And it may be considered as a novel tumor marker to find both a new anti-oncogene and relative factors of invasion and metastasis of laryngeal carcinoma.</p>

Decreased expression of DICER1 in gastric cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The role of epigenetics in gene expression regulation and development significantly enhances our understanding of carcinogenesis. All the tumor related genes may be the target of epigenetical or genetic regulation. We selected some epigenetically regulated genes for cDNA array analysis and observed variability in the expression of the DICER1 gene in distinct stages of gastric cancer. The aim of this study was to assess the correlation between the expression of DICER1, an epigenetically regulated gene, and gastric cancer.</p><p><b>METHODS</b>To detect the expression of 506 tumor-associated genes, including DICER1, in the matched cancerous mucosa, pre-malignant lesion (adjacent mucosa), non-cancerous gastric mucosa and distant lymphocyte metastatic lesion in 3 cases of gastric cancers using cDNA array. DICER1 mRNA expression and DICER1 protein expression were further analyzed by Real-time PCR and Western blot in 32 cases of progressive gastric cancer. DICER1 protein expression was also detected in 33 early and 30 progressive gastric cancers by the immunohistochemistry (IHC) method.</p><p><b>RESULTS</b>In 3 cases of gastric cancer cDNA array showed dramatically decreased expression of DICER1 in pre-malignant lesion, cancerous mucosa and distant lymphocyte metastatic lesions compared with matched noncancerous gastric mucosa, pre-malignant lesion and cancerous mucosa. Real-time PCR results showed that the expression level of DICER1 mRNA in gastric cancer was significantly down-regulated compared to normal gastric tissue (P < 0.05). The IHC assay also showed that the expression of DICER1 was significantly decreased in progressive gastric cancer. Among the 63 cases of gastric cancers, 13/33 early (39.4%) and 19/30 (63.3%) progressive cancers showed negative expression of DICER1 (50.8%). The difference in expression of DICER1 between early and progressive gastric cancers was significant (P < 0.01). The result of Western blotting showed that DICER1 protein was down-regulated significantly in advanced gastric cancer (P < 0.05).</p><p><b>CONCLUSIONS</b>DICER1 expression is decreased during the progression of gastric cancer, especially in progressive gastric cancers, which indicating DICER1 may play an important role in the development of cancer and the epigenetical regulation involved.</p>

Proteomic analysis of the ankle joint bone, ankle joint tissue and spinal cord of clubfoot-like deformity in rat fetuses / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the etiology of idiopathic talipes equinovarus (ITEV) in all-trans retinoic acid (ATRA) induced clubfoot-like deformity in rat fetuses with two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS).</p><p><b>METHODS</b>Clubfoot-like deformity model in rat fetuses was induced with ATRA (135 mg/kg) in gestation day (GD10) pregnant Wistar rats. 2-DE was applied to separate the total proteins of ankle joint tissue, ankle joint bone and spinal cord of the animal models. The Coomassie Brilliant Blue staining gels were analyzed by 2-DE software PDQuest 7.1.0. Selected differential protein spots were identified with peptide mass fingerprinting based on matrix-assisted laser adsorption/ionization time-of-flight mass spectrometry and database searching. xiap, tnnt1 and col2 alpha 1, three genes of the differential proteins, were identified furthermore. Apoptosis study was made in terminal deoxynucleotidyl transferase nick end labeling.</p><p><b>RESULTS</b>There were many differential expressed proteins in the clubfoot-like deformity model. Out of the differentially expressed proteins,16 protein spots were identified to be differentially expressed in the clubfoot-like deformity model with MS. Three of the 16 protein spots, xiap, tnnt1 and col2 alpha 1 were confirmed to be significantly down-regulated by the RT-PCR, and Xiap was further confirmed to be significantly down-regulated with immunohistochemistry. Another randomly selected gene, ngfr, did not express differently in ATRA-induced clubfoot-like deformity in rat fetuses. The rates of the apoptosis in the spinal, bone of the clubfoot-like deformity fetuses was 5.4 and 10 times of those of the normal fetuses respectively.</p><p><b>CONCLUSION</b>The results suggest that there are certain differently expressed proteins in ankle joint tissue, ankle joint bone and spinal cord of the ATRA-induced clubfoot-like deformity in rat fetuses, and Xiap, sTnT, and Col2 alpha 1 show a significant correlation with ITEV. Ngfr is not correlation with ITEV. Apoptosis plays a key role in the development of ITEV and related to the decreased expression of the Xiap.</p>

Analysis of chromosome aberrations in the cell derived from primary cell culture of laryngeal carcinoma and the Hep-2 cell line / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To search for characteristic chromosome changes in primary laryngeal squamous cell carcinoma (LSCC) and Hep-2 cell line and to realize the relationship between the cytogenetic abnormality and the pathogenetic mechanism in LSCC.</p><p><b>METHODS</b>The fresh resulted samples of LSCC were analyzed with an improved primary cell culture for chromosome preparation and G-banding technique. Hep-2 cell line was analyzed by high resolution banding technique. Molecular cytogenetics analysis was made by chromosome 6 painting probe.</p><p><b>RESULTS</b>Four primary LSCC succeeded in primary cell culture and obtained metaphases, one was tetraploid, the other three were triploid. The chromosome mode of Hep-2 cell line was from 68 to 75 and fifteen marker chromosomes were found. The most structural abnormalities of chromosome in primary LSCC and HEP-2 cell line were unbalance translocation, terminal deletion and isochromosome. The complicate aberration in chromosome 6 was common in LSCC and Hep-2.</p><p><b>CONCLUSION</b>6q-, I(5p), 17p-, 5q- are considered as characteristic chomosome changs in LSCC. Fluorescence in situ hybridization (FISH) may enhance the ability of detecting complicated chromosome rearrangements and marker chromosomes, which could provide more value data to verify the chromosome characteristic aberration in LSCC.</p>

Average-12.9 chromosome imbalances coupling with 15 differential expression genes possibly involved in the carcinogenesis, progression and metastasis of supraglottic laryngeal squamous cell cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>With the objective of discovering novel putative chromosomal regions and special genes involved in the carcinogenesis, progression and metastasis of laryngeal squamous cell cancer (LSCC).</p><p><b>METHODS</b>DNA copy profile of LSCC were obtained and analyzed by comparative genomic hybridization (CGH) and a computerized digital image analysis system. cDNA microarray of LSCC was performed and the profile was analyzed by Hierarchical clustering.</p><p><b>RESULTS</b>CGH analysis showed average-12.9 gains and losses of chromosomes in LSCC. Relatively high frequencies of gains were found at 3q15-21 (14/18), 5p12-13 (11/18), 8q22-24 (6/18), 11q12-13 (8/18), 15q21-23 (7/18) and 18p11 (8/18), while those of losses at 1p13-21 (8/18), 3p21-23 (14/18), 5q21-22 (14/18), 9p12-pter (11/18) and 13q21-31 (8/18). Hierarchical clustering analysis showed that the differentially expressed genes were segregated into three groups. Three genes differentially expressed in process I (normal tissue to cancer) and process II (cancer to lymph node metastasis), and the Cy5/Cy3 ratios of twelve genes were either higher than 5.0 or lower than 0.2 in process I or process II. The fifteen special genes were first reported possibly to be the relationships with LSCC. In particular, 4 genes of them, which were cytochrome C oxidase Va, PPBP, EPHX2 and PON1, were first reported to correlate with tumorigenesis. SH3GL2, which was one of the 15 special genes, was located at one of the special chromosome regions, 9p12-pter.</p><p><b>CONCLUSION</b>The important genes and special chromosomal aberrances might provide us a clue for further investigation of carcinogenesis, progression and metastasis in LSCC.</p>

Gene expression patterns in gastric cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify gene expression patterns in distinct stages of intestinal-type gastric cancer(GC).</p><p><b>METHODS</b>Gene expression patterns of distinct stages of intestinal-type GC samples from 3 patients were compared with cDNA microarray, which contained 576 genes. There were 506 target genes, which included 51 genes identified from our previous experiment with suppression subtractive hybridization(SSH) and other 455 genes chosen for their important roles in cancers. Hierarchical clustering was performed to clarify genes in association with distinct stages of GC.</p><p><b>RESULTS</b>One hundred and eighty-one differentially expressed genes with average Cy5:Cy3 ratios higher than 2.0 or lower than 0.5 in at least one stage of GC were identified by cDNA microarray. Among them, 48 genes were up-regulated and 133 down-regulated. Hierarchical clustering analysis separated the differentially expressed genes in different stages of GC into 5 main characteristic groups. Some important differentially expressed genes in different stages of GC were identified, such as SEC23IP, LIPF, ES(BQ291520), SLC5A1, PG(encoding similar to pepsin A precursor), CXCR4, DICER1, SH3GL2, and IGF2R.</p><p><b>CONCLUSION</b>The differentially expressed gene patterns and some important genes were identified, which might be useful in further study on carcinogenesis, progression and metastasis of intestinal-type GC.</p>

The investigation of STK15 gene amplification and overexpression in laryngeal squamous cell carcinoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the role of STK15 gene amplification and overexpression to genesis and development of laryngeal squamous cell carcinoma (LSCC).</p><p><b>METHODS</b>STK15 gene amplification in 40 cases carcinoma tissues and normal tissues as control was detected by differential PCR approach. STK15 mRNA and protein levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry method.</p><p><b>RESULTS</b>In 40 LSCC cases, STK15 gene amplification was found in 14 tumor tissues(35%), mRNA overexpression in 27 tumor tissues(67.5%), and protein upregulated in 29 tumor tissues(72.5%). Statistics analysis showed that STK15 gene amplification and mRNA overexpression were obviously associated to differentiation degree of LSCC, and protein overexpression was closely associated with both differentiation degree and pathological grades of LSCC.</p><p><b>CONCLUSION</b>This research results suggest that STK15 gene amplification contributes to its mRNA and protein overexpression through affecting the exact replication of centrosome and separation of chromosomes. STK15 gene thus plays a role in LSCC oncogenesis and malignant progression.</p>

Mutation of p53 and overexpression of STK15 in laryngeal squamous-cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship between p53 gene mutations and STK15 abnormal expression in the development of human laryngeal squamous-cell carcinoma (LSCC).</p><p><b>METHODS</b>LSCC tissues and matched normal tissues were taken during operation from 55 patients without previous chemotherapy or radiotherapy. Following polymerase chain reaction amplification direct sequencing single strand conformational polymorphism (PCR-SSCP) combined with silver staining were used to detect mutations of p53 gene in exons 7 and 8 (p53E7 and p53E8) using genomic DNA from 110 specimens including 55 LSCC tissues and 55 matched normal tissues. STK15 expression were evaluated by RT-PCR with beta-actin as internal control.</p><p><b>RESULTS</b>The mutation rate of p53E7 was 30.9% (compared to normal tissues, chi(2) = 8.66, P < 0.01). There was no mutation in p53E8. In 38 of the 55 cases (69.1%), the STK15 mRNA expression level was higher than that of the paired normal tissue. The STK15 to beta-actin ratio of average density value was 1.22 +/- 0.49 in the cancer tissue, and 0.99 +/- 0.54 in the normal tissues (t = 4.539, P < 0.01). In 14 of the 17 cases (82.4%) with p53E7 mutations, the STK15 expression was higher than that of normal tissue. In the 38 cases with STK15 over-expression, p53E7 mutation was found in 14 cases (36.8%). The rate of concurrence of p53E gene mutations and STK15 over-expression (25.5%) was higher than that of only p53E gene mutations (chi(2) = 26.025, P < 0.01).</p><p><b>CONCLUSION</b>There is significant association between p53 gene mutation and STK15 over-expression in laryngeal squamous-cell carcinoma.</p>