[Show abstract][Hide abstract] ABSTRACT: Despite advances in therapy, survival among patients with locally advanced squamous cell carcinoma of tongue (TSCC) and cervical lymph node metastasis remains dismal. Here, we estimated the functional effect of AEG-1 on TSCC metastasis and explored the molecular mechanism by which AEG-1 stimulates epithelial-mesenchymal transition (EMT). We initially found that AEG-1 mRNA levels were much higher in metastatic TSCC than in non-metastatic TSCC and that AEG-1 expression strongly correlates with EMT status. Receiver operating characteristic analysis showed that the combined AEG-1 and EMT statuses are predictive of the survival rate among TSCC patients. In addition, AEG-1 knockdown inhibited EMT in cultured TSCC cell lines and in a xenograft-mouse model. Recombinant AEG-1 activated Wnt/PCP-Rho signaling, and its stimulatory effects on TSCC cell invasiveness and EMT were reversed by an anti-Wnt5a neutralizing antibody or by inhibition of Rac1 or ROCK. These results highlight the critical stimulatory effect of AEG-1 on cancer cell invasiveness and EMT and indicate that AEG-1 may be a useful prognostic biomarker for TSCC patients.
[Show abstract][Hide abstract] ABSTRACT: Recent observations indicate the vital role of heparanase in tumor lymphangiogenesis. Moreover, heparanase is involved in angiogenesis in esophageal cancer through induction of COX-2. However, it is unclear whether heparanase is also associated with COX-2 in lymphangiogenesis of cervical cancer. In this study, heparanase, COX-2 and VEGF-C expression were examined in 80 cervical cancer cases by immunohistochemical staining. We also studied the correlation of heparanase and COX-2 expression with lymphangiogenesis of cervical cancer quantified as lymphatic vessel density. Our results showed that expressions of heparanase and COX-2 were associated with lymphangiogenesis of cervical cancer. Furthermore, a significant correlation was found between the expression of heparanase and COX-2 (P < 0.0001). Heparanase is positively correlated with expressions of COX-2 and VEGF-C. These findings revealed that heparanase may play important function in lymphangiogenesis of cervical cancer via the regulation of COX-2 expression.
No preview · Article · Dec 2014 · Medical Oncology
[Show abstract][Hide abstract] ABSTRACT: Endometrial adenocarcinoma is the most common tumour of the female genital tract in developed countries, and oestrogen receptor (ER) signalling plays a pivotal role in its pathogenesis. When we used bioinformatics tools to search for the genes contributing to gynecological cancers, the expression of Olfactomedin 4 (OLFM4) was found by digital differential display to be associated with differentiation of endometrial adenocarcinoma. Aberrant expression of OLFM4 has been primarily reported in tumours of the digestive system. The mechanism of OLFM4 in tumuorigenesis is elusive. We investigated OLFM4 expression in endometrium, analysed the association of OLFM4 with ER signalling in endometrial adenocarcinoma, and examined the roles of OLFM4 in endometrial adenocarcinoma. Expression of OLFM4 was increased during endometrial carcinogenesis, linked to the differentiation of endometrioid adenocarcinoma, and positively related to the expression of oestrogen receptor-α (ERα) and progesterone receptor. Moreover, ERα-mediated signalling regulated expression of OLFM4, and knockdown of OLFM4 enhanced proliferation, migration and invasion of endometrial carcinoma cells. Down-regulation of OLFM4 was associated with decreased cumulative survival rate of patients with endometrioid adenocarcinoma. Our data suggested that impairment of ERα signal-mediated OLFM4 expression promoted the malignant progression of endometrioid adenocarcinoma, which may have significance for the therapy of this carcinoma.
Preview · Article · Feb 2014 · Journal of Cellular and Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Aim:
Protein 14-3-3γ is an important member of the 14-3-3 family that play important roles in the regulation of various cellular processes. The aim of the study is to investigate the association between 14-3-3γ expression and the clinicopathological features of patients with breast cancer.
The expression of 14-3-3γ was detected by Western blot in both foci of breast cancer and adjacent non-cancerous tissues. In addition, 14-3-3γ expression was analyzed by immunohistochemistry in 60 clinicopathologically characterized breast cancer cases. The association of 14-3-3γ expression with survival of the patients were analyzed.
The expression level of 14-3-3γ protein in breast cancer were significantly higher than that in non-cancerous mammary gland tissues. Moreover, high expression of 14-3-3γ correlated with tumor size and tumor grade (all P<0.05). Patients with high 14-3-3γ expression had worse overall survival rate than that with low expression (P < 0.05). Furthermore, multivariate analysis showed that 14-3-3γ expression was an independent predictor of overall survival (HR, 0.196; 95%CI, 0.043-0.892; P = 0.035).
Our data suggest for the first time that the increased expression of 14-3-3γ in breast cancer is associated significantly with tumor progression and poor prognosis. 14-3-3γ may be a novel and potential prognostic marker for breast cancer.
[Show abstract][Hide abstract] ABSTRACT: Recent studies have emphasized causative links between aberrant microRNA expression patterns and cancer progression. miR-183 is dysregulated in certain types of human cancers. The expression pattern, clinical significance, and biological role of miR-183 in osteosarcoma, however, remain largely undefined. In this paired analysis, we found that miR-183 was markedly down-regulated in osteosarcoma cells and tissues compared with matching normal bone tissues using RT-qPCR. Statistical analyses revealed that the expression levels of miR-183 significantly correlated with lung metastasis as well as with local recurrence of osteosarcoma. miR-183 expression was inversely correlated with Ezrin mRNA and protein expression levels in osteosarcoma cells as well as in a subset of primary osteosarcoma. Ectopically expressed miR-183 inhibited migratory and invasive abilities of osteosarcoma cells, whereas knockdown of endogenous miR-183 significantly enhanced these abilities. Using a luciferase reporter carrying the 3'-untranslated region (3'-UTR) of Ezrin, we identified Ezrin as a direct target of miR-183. Moreover, ectopic expression of Ezrin could significantly rescue miR-183-suppressed migration and invasion. Of interest, suppression of Ezrin by miR-183 caused a reduction of phosphorylated p44/42 (p-p44/42). Finally, suppression of Ezrin by RNAi mimicked miR-183 action in the suppression of migration and invasion, which was associated with down-regulation of p-p44/42. Taken together, these results suggest that as a tumor suppressor miRNA, miR-183 plays an important role in the aggressiveness of osteosarcoma.
No preview · Article · Apr 2012 · American Journal Of Pathology
[Show abstract][Hide abstract] ABSTRACT: Previous studies have demonstrated that the expression of prostate-specific membrane antigen (PSMA) is restricted to endothelium from tumor-associated neovasculature. But the expression of PSMA in osteosarcoma and its clinical significance are unknown. Using immunohistochemical analysis and quantum dot probes, we found that 46.7% (21/45) of the osteosarcoma showed positive staining for PSMA while no PSMA staining in osteofibrous dysplasia. The expression and localization of PSMA was confirmed by CD34 staining. More importantly, the expression of PSMA is correlated with tumor size, pulmonary metastasis and worse survival (survival rate 63.2% in the PSMA-negative group versus 36.6% in the PSMA-positive group). Thus, PSMA could be used as an independent prognostic marker for the osteosarcoma patients, and PSMA staining in tumor-associated neovasculature may be a potential target for antineovasculature-based therapy in osteosarcoma.
No preview · Article · Oct 2011 · Medical Oncology
[Show abstract][Hide abstract] ABSTRACT: Olfactomedin 4 (OLFM4) is expressed in gastrointestinal cancers and related to progression and differentiation of these malignancies. However, whether OLFM4 contributes to tumorigenesis of other tissues has not been thoroughly investigated. The purpose of the study was to investigate OLFM4 expression in cervical epithelium and its association with progression of cervical neoplasia and differentiation of cervical carcinomas.
Immunohistochemistry and real-time reverse transcription-polymerase chain reaction were used to evaluate the expression and distribution of OLFM4 in cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinomas (ISCCs).
The overall positive OLFM4 staining levels in normal cervical epithelia, CIN I, CIN II, CIN III, and ISCCs are 22.0%, 94.2%, 93.7%, 94.6%, and 96.7%, respectively. The intensity of OLFM4 staining was enhanced according to increased pathologic grade of cervical squamous intraepithelial lesion. The immunoreactivity to OLFM4 was stronger in well-differentiated ISCCs than in poorly differentiated ISCCs.
Olfactomedin 4 expression has been associated with progression of CIN and differentiation of cervical cancer. The results provide new evidence that OLFM4 plays an important role in tumorigenesis in the female reproductive tract.
No preview · Article · Feb 2011 · International Journal of Gynecological Cancer
[Show abstract][Hide abstract] ABSTRACT: Osteogenesis imperfecta (OI) is an inherited bone disease caused by mutations in collagen genes. Because these mutations occur at a wide variety of sites in the genes and differ among populations, we studied the COL1A1 gene in Chinese with OI and compared the results with findings form other populations.
COL1A1 gene mutations were detected by polymerase chain reaction and sequencing from 3 unrelated families and 1 sporadic case in Chinese.
Four COL1A1 mutations that were novel were found. The patients' clinical characteristics were variable, even within the same family. Notably, some of the novel COL1A1 variants were at the same nucleotide positions as previously described but with different nucleotide changes. In addition, we also found 1 patient with OI with 2 mutations in the same haplotypes.
We discuss the differences in phenotype related to the specific mutation sites. Although there have been many reports on mutations of COL1A1 and COL1A2, few cases have been reported in Chinese. Our data showed that the COL1A1 gene mutation might also play an important role in OI among Chinese. The Han Chinese represent a quarter of the world's population, and we believe that our new data contributes to fill in the type I collagen mutation map. We thought that the patient with OI could have 2 mutations in the same haplotypes, without limit to 1 mutation.
No preview · Article · Jul 2009 · Journal of Investigative Medicine
[Show abstract][Hide abstract] ABSTRACT: To study the gene mutation of collagen, type I, alpha 1 (COL1A1) associated with the clinical characterization of a Chinese family with type I osteogenesis imperfecta (OI).
Polymerase chain reaction, DNA sequencing and restriction endonuclaese analysis were used to check all the members in the family with OI and 50 normal control people for detecting the mutation of COL1A1 gene.
A 2461G>A (G821S) mutation was found and identified in COL1A1 gene of OI patients, to whom the individual clinical characterization was displayed, however. And the other members in the family with OI and the control did not have such gene mutation as 2461G>A.
The mutation of COL1A1 gene is one of the OI etiologic causes in China. There is no simple universal linkage between such gene changes and OI phenotype, but which not only involved in the OI genotype but the genetic background as well.
No preview · Article · Apr 2006 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics
[Show abstract][Hide abstract] ABSTRACT: Osteogenesis imperfecta (OI) is a congenital disease of connective tissue of increased bone fragility and low bone mass, most often caused by single amino acid substitution of glycine residues in the collagen, type I, alpha 1 protein (COL1A1) gene or the collagen, type I, alpha 2 protein (COL1A2) gene, encoding type I procollagen chains. We describe here the clinical, biochemical, and molecular characterization of a family with type I OI in China and would like to explore whether the biochemical characterization of OI in China is different from that in other countries.
Through clinical research, we study the clinical characteristic of the OI household. Genomic DNA was isolated from peripheral blood lymphocytes of the proband and his family members by saturation hydroxybenzene-chloroform methods; amplification of target COL1A1 gene by Polymerase chain reaction with 23 pairs of different primers; purification; direct sequencing of the Polymerase chain reaction product. According to the mutation site, we took restriction enzyme analysis to 50 normal control people.
We found a G and A heterozygosis mutation at the exon 48 causing an a1 (I) p. G1157D substitution in the proband and his sister who is also a sufferer of OI. At the same time, other normal people in the family and other normal control people do not have this change.
This is the first delineation of an aspartic acid substitution in new site of the a1 (I) chain causing nonlethal osteogenesis imperfecta. Only nine aspartic acid substitution in type I collagen has been fully reported in the world. Now we revealed a new nosogenesis of OI. Since only few of nucleotide changes in type I collagen glycine codons would result in an aspartic acid substitution, these are predicted to be infrequent. Furthermore, it is possible to suggest that nosogenesis of OI in china is different from other countries.
No preview · Article · Feb 2006 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: To observe the changes in histopathology and clinical effect after the treatment of superficial scars in human faces and exposed parts of human extremities with crystallitic dermabrasion.
The machine made in Italy can produce the high speed crystallite to the surface of the scar, resulting in the alveolate wounds. At the same time the crystallitic drill make the accidental scar smooth.
Two thousands and five hundreds and thirty eight suffers were treated for 2-10 times. The appearance of the scars was improved. Six patients complicated with milium, Eleven got hypopigmentation, eight got hypomelanotation. Eighty percent patients of this groups got pigmentation after the treatment. This signs disappeared or improved after 2-6 months. Histopathology demonstrated the scar area became small, the fibroblasts increased remarkably and the collagenous fiber arranged regularly. The cells in the stratum spinosum proliferated actively.
Crystallitic dermabrasion is a simple and safe method for the treatment of skin superficial scars.
No preview · Article · Jun 2005 · Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery
[Show abstract][Hide abstract] ABSTRACT: Endothelial dysfunction is the earliest marker for age-related abnormalities in vascular function, and examination of endothelial function has important clinical relevance. The present study was performed to evaluate effects of aging on arterial elasticity by using pulse waveform analysis and to investigate whether the changes in arterial elasticity might be used as a noninvasive measure for endothelial dysfunction.
A total of 24 healthy male volunteers were divided into young (n = 12) and elderly (n = 12) groups. Endothelial function was evaluated by delivering acetylcholine (Ach) and sodium nitroprusside (SNP) to the forearm vessels using iontophoresis, respectively, and measured blood flow using laser Doppler fluximetry. Large and small artery elasticity indices were noninvasively assessed using pulse wave analysis.
Basal blood flow was similar between the young and elderly groups (14.58 +/- 3.4 v 13.52 +/- 3.41 PU, P = NS). Peak blood flow induced by Ach was significantly reduced in the elderly group compared with the young group (83.4 +/- 11.9 v 93.75 +/- 10.87 PU, P < .05). However, peak blood flow induced by SNP was similar in the two groups (119.17 +/- 16.76 v 128.33 +/- 21.29 PU, P = NS). In parallel, C1 large artery elasticity and C2 small artery elasticity indices were significantly reduced in the elderly group compared with the young group (11.42 +/- 1.67 v 16.75 +/- 2.09 mL/mm Hg x 10, P < .001; and 7.67 +/- 1.56 v 10.75 +/- 1.86 mL/mm Hg x 100, P < .001, respectively). The Ach-induced peak blood flow correlated with C1 large and C2 small artery elasticity indices.
Advancing age is associated with endothelial dysfunction and reduced arterial elasticity. Reduced arterial elasticity parallels changes in impaired endothelium dependent vasodilation. It appears that reduced arterial elasticity may be used as a noninvasive measure for the determination of endothelial function.
No preview · Article · Sep 2004 · American Journal of Hypertension