Biomedical subjects

Yimin Wang

Publications and source records attributed to Yimin Wang.

At least 19 recordsLinked to original sources

PubMed2026

Effect of renin-angiotensin system inhibitors on survival in glioma patients: A systematic review and meta-analysis.

PURPOSE: To evaluate the effect of renin-angiotensin system inhibitors (RASIs) on the survival outcomes of glioma patients, determine whether using RASIs correlates with survival benefit, and provide evidence-based guidance for the clinical treatment. METHODS: Studies assessing the effects of using RASIs versus non-use in glioma patients were retrieved from the PubMed, Cochrane Library, Web of Science, and Embase databases from inception to April 17, 2024. The included studies reported hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS), as well as the effect on brain edema and steroid dosing in patients. RESULTS: Seven articles involving 2660 patients were included in this study. Pooled results indicated there was no significant difference in OS (HR = 0.89, 95% CI 0.75-1.06, P = 0.204) or PFS (HR = 0.98, 95% CI 0.82-1.18, P = 0.847) between RASIs-treated patients and non-RASIs-treated patients. Sensitivity analysis identified the ACEIs-focused trial reported by Happold et al. as a major contributor to inter-study heterogeneity. Subgroup analyses revealed that in recurrent glioblastoma, pooled OS was significantly longer in RASIs-treated patients than non-RASIs-treated patients (HR = 0.70, 95% CI 0.54-0.92, P = 0.01). Similarly, compared with bevacizumab monotherapy, bevacizumab combined with RASIs significantly extended OS in glioblastoma patients (HR = 0.73, 95% CI 0.63-0.86, P < 0.001). CONCLUSION: The results revealed that treatment with RASIs may show a trend toward prolonged overall survival (OS) in patients with glioma. For patients with glioblastoma, RASI therapy could prolong OS in those with recurrent disease. Furthermore, compared with bevacizumab monotherapy, the combination of RASIs and bevacizumab was associated with improved OS in glioblastoma patients.

Humans↗

PubMed2007

Association of MTHFR C677T and SHMT(1) C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China.

OBJECTIVE: To assess the association between the C to T transition in the methylenetetrahydro folate reductase gene (MTHFR C677T) and the C to T transition in the serine hydroxymethyltransferase ( 1 )gene (SHMT ( 1 ) C1420T) and the increased risk of carcinogenesis of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of high incident region of Northern China. METHODS: The polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism and PCR-confronting two-pair primers analysis respectively among 1051 cancer patients (584 ESCC and 467 GCA) and 540 healthy controls. RESULTS: The MTHFR 677T/T genotype significantly increased susceptibility to both ESCC and GCA compared with the C/C genotype, the adjusted OR was 2.13 (95% CI = 1.50-3.02) and 1.28 (95% CI = 1.07-1.53, respectively. For the SHMT ( 1 ) C1420T polymorphism, the C/C genotype was significantly associated with the increased risk of ESCC and GCA, compared with the C/T genotype (the adjusted OR = 1.43 and 1.35, 95% CI = 1.02-2.00 and 1.11-1.63, respectively). The interactive influence of the MTHFR and SHMT ( 1 ) polymorphisms in the risk of ESCC and GCA was also observed. CONCLUSION: The association between the MTHFR C677T and SHMT ( 1 ) C1420T polymorphisms and the risk of ESCC and GCA was demonstrated.

Adenocarcinoma↗

PubMed2007

The Ca2+-activated K+ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration.

Brain damage and disease involve activation of microglia and production of potentially neurotoxic molecules, but there are no treatments that effectively target their harmful properties. We present evidence that the small-conductance Ca2+/calmodulin-activated K+ channel KCNN4/ KCa3.1/SK4/IK1 is highly expressed in rat microglia and is a potential therapeutic target for acute brain damage. Using a Transwell cell-culture system that allows separate treatment of the microglia or neurons, we show that activated microglia killed neurons, and this was markedly reduced by treating only the microglia with a selective inhibitor of KCa3.1 channels, triarylmethane-34 (TRAM-34). To assess the role of KCa3.1 channels in microglia activation and key signaling pathways involved, we exploited several fluorescence plate-reader-based assays. KCa3.1 channels contributed to microglia activation, inducible nitric oxide synthase upregulation, production of nitric oxide and peroxynitrite, and to consequent neurotoxicity, protein tyrosine nitration, and caspase 3 activation in the target neurons. Microglia activation involved the signaling pathways p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB), which are important for upregulation of numerous proinflammatory molecules, and the KCa3.1 channels were functionally linked to activation of p38 MAPK but not NF-kappaB. These in vitro findings translated into in vivo neuroprotection, because we found that degeneration of retinal ganglion cells after optic nerve transection was reduced by intraocular injection of TRAM-34. This study provides evidence that KCa3.1 channels constitute a therapeutic target in the CNS and that inhibiting this K+ channel might benefit acute and chronic neurodegenerative disorders that are caused by or exacerbated by inflammation.

Animals↗

PubMed2006

Association between the functional polymorphism in the matrix metalloproteinase-7 promoter and susceptibility to adult astrocytoma.

To study the association between the A to G transition at the -181-bp position in the promoter of matrix metalloproteinase-7 gene (MMP-7-181A/G) and susceptibility to adult astrocytoma, the MMP-7-181A/G polymorphism was genotyped by PCR-RFLP analysis among 221 adult astrocytoma patients and 366 healthy controls in a population of northern China. The result showed that the overall distribution of the MMP-7 genotypes among astrocytoma patients and healthy controls was significantly different (P<0.001). Compared with the A/A genotype, the G/G genotype significantly increased the risk to the development of astrocytoma (age and gender adjusted OR=2.77, 95% CI=1.27-6.02), while the MMP-7 A/G genotype only marginally increased the risk of developing this cancer (age and gender adjusted OR=1.66, 95% CI=0.99-2.84). Stratification analysis showed that the G/G genotype significantly increased the risk of astrocytoma only among male subjects (age adjusted OR=3.24, 95% CI=1.12-9.41) and individuals younger than 45 years (age and gender adjusted OR=3.16, 95% CI=1.09-9.16). When stratified by histological grades, a significant higher risk for developing grade II astrocytoma was observed among individuals harboring the A/G genotype (age and gender adjusted OR=2.06, 95% CI=1.05-4.05), while an about 3-fold elevation of risk to develop grades II, III, and IV astrocytomas was observed among individuals with the G/G genotype. The present result, for the first time, suggested that the MMP-7-181A/G polymorphism might be associated with the susceptibility to adult astrocytoma.

Adult↗

PubMed2005

The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma.

An A to G transition at the 181 base pair position upstream of the transcription initiation site of the matrix metalloproteinase-7 (MMP-7) gene (-181A/G) may modify the development and progression of some diseases via influencing the transcription activity of the promoter. To assess the effects of the functional single nucleotide polymorphism on cancer susceptibility and progression, the MMP-7 -181A/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis among 258 patients with esophageal squamous cell carcinoma (ESCC), 201 patients with gastric cardiac carcinoma (GCA), 243 patients with non-small cell lung carcinoma (NSCLC) and 350 healthy individuals without cancer. The result showed that the frequency of the -181G allele in ESCC, GCA and NSCLC patients was significantly higher than that in healthy controls (P = 0.019, 0.023 and 0.004, respectively). Compared with the A/A genotype, genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to all three tumors, with adjusted odds ratio of 1.83 (95% CI = 1.12-2.99) for ESCC, 1.96 (95% CI = 1.17-3.29) for GCA and 2.00 (95% CI = 1.23-3.24) for NSCLC. Stratification analysis showed that smoking did not significantly influence the association between the MMP-7-181A/G and GCA or NSCLC, while the -181G allele only significantly increased susceptibility to ESCC among smokers. In addition, association between the -181G allele and susceptibility to ESCC and GCA showed significance only among individuals with family history of upper gastrointestinal cancer. The correlation of the MMP-7-181A/G polymorphism with potential of lymphatic metastasis was not observed in all three tumors. The study suggested that, the MMP-7-181A/G polymorphism might be a candidate marker for predicting individuals who are at higher risk to certain tumors but might not be used to predict potential of lymphatic metastasis in ESCC, GCA and NSCLC.

Adenocarcinoma↗

PubMed2005

Overexpression, purification and crystallographic analysis of a unique adenosine kinase from Mycobacterium tuberculosis.

Adenosine kinase from Mycobacterium tuberculosis is the only prokaryotic adenosine kinase that has been isolated and characterized. The enzyme catalyzes the phosphorylation of adenosine to adenosine monophosphate and is involved in the activation of 2-methyladenosine, a compound that has demonstrated selective activity against M. tuberculosis. The mechanism of action of 2-methyladenosine is likely to be different from those of current tuberculosis treatments and this compound (or other adenosine analogs) may prove to be a novel therapeutic intervention for this disease. The M. tuberculosis adenosine kinase was overexpressed in Escherichia coli and the enzyme was purified with activity comparable to that reported previously. The protein was crystallized in the presence of adenosine using the vapour-diffusion method. The crystals diffracted X-rays to high resolution and a complete data set was collected to 2.2 A using synchrotron radiation. The crystal belonged to space group P3(1)21, with unit-cell parameters a = 70.2, c = 111.6 A, and contained a single protein molecule in the asymmetric unit. An initial structural model of the protein was obtained by the molecular-replacement method, which revealed a dimeric structure. The monomers of the dimer were related by twofold crystallographic symmetry. An understanding of how the M. tuberculosis adenosine kinase differs from the human homolog should aid in the design of more potent and selective antimycobacterial agents that are selectively activated by this enzyme.

Adenosine Kinase↗

PubMed2005

Ultrahigh-resolution optical coherence tomography with a fiber laser source at 1 microm.

We report a compact, high-power, fiber-based source for ultrahigh-resolution optical coherence tomography (OCT) near 1 microm. The practical source is based on a short-pulse, ytterbium-doped fiber laser and on generation of a continuum spectrum in a photonic crystal fiber. The broadband emission has an average power of 140 mW and offers an axial resolution of 2.1 microm in air (<1.6 microm in biological tissue). The generation of a broad bandwidth is robust and efficient. We demonstrate ultrahigh-resolution, time-domain OCT imaging of in vitro and in vivo biological tissues.

Equipment Design↗

PubMed2005

No association between the C-1562T polymorphism in the promoter of matrix metalloproteinase-9 gene and non-small cell lung carcinoma.

The matrix metalloproteinases (MMPs) are a family of highly conserved metal-dependent proteolytic enzymes, their main function is to degrade different components of extracellular matrix (ECM). Moreover, they play roles in regulation of cell growth, apoptosis, angiogenesis and immune surveillance. Natural sequence variations in the MMP genes may result in differential expression of MMPs in different individuals and therefore may be associated with the development and progression of diseases. The aim of this study is to assess the effects of the C-1562T polymorphism in the MMP-9 promoter on the risk of occurrence and lymphatic metastasis of non-small cell lung carcinoma (NSCLC). The MMP-9 genotyping was performed in 243 pathologically diagnosed NSCLC patients and 350 healthy controls without overt cancer by using polymerase chain reaction-restriction fragment length polymorphism analysis. The distribution of the MMP-9 genotypes in NSCLC patients and healthy controls was in consistent with Hardy-Weinberg equilibrium. The frequency of the C/C, C/T and T/T genotypes in healthy controls was 79.4, 20.6 and 0%, respectively. Neither the overall genotype nor allelotype distribution in NSCLC patients showed significant difference from that in healthy controls (P=0.21 and 0.43, respectively). Compared with the C/C genotype, genotypes with the T allele did not show significant influence on the risk of NSCLC development (age and gender adjusted OR=1.13, 95% CI=0.76-1.68). Stratification by onset age, smoking status and tumor histological type also showed no association between the MMP-9 polymorphism and the risk of NSCLC. Furthermore, the genotype distribution between NSCLC patients with and without lymphatic metastasis was not significantly different. Therefore, the present study suggests that the MMP-9 C-1562T polymorphism may not be used as a useful marker to predicate susceptibility and lymphatic metastasis in NSCLC.

Adenocarcinoma↗

PubMed2005

Surgical correction of orbital and periorbital deformities using lamella and complex osteotomies in both orbital rim and wall.

PURPOSE: For dealing with the problems in orbital and periorbital deformities. METHODS: In orbital deformities such as hypertelorism, orbital dystopia, radiated orbit, and secondary deformities of traumatic orbit, the authors used lamella osteotomies of either orbital rim and wall or complex osteotomies in both adjacent orbital rims and walls with bicoronal incision and galea aponeurotica dissection. In most of the cases, the fragments of complex osteotomies were repositioned with rigid fixation. RESULTS: Best results with nearly normal orbital volumes, better contour of orbit and midface, and improved eyelids and vision were achieved in 44 cases. There were 5 cases of supraorbital osteotomy (intracranial routine), 8 cases of medial orbital osteotomy, 3 cases of inferior orbital osteotomy, and 28 cases of both lateral and inferior orbital osteotomy in the series. No complications occurred. Clinical measurement was achieved in both pre- and postoperative osteotomies. According to comparative recordings, such as cephalometric measurement of the interorbital distance, exophthalmic measurement with Hertel exophthalmometer, the angle between orbital horizontal level and bilateral tragus linkage, and the linear distance between lateral canthus and tragus, the gap difference between pre- and postoperative data were achieved. The orbital and midface appearance has improved significantly. CONCLUSIONS: Lamella and complex osteotomies of orbital rim and wall were proved to be save and effective for correction of most deformities of the orbital and periorbital region.

Adolescent↗

PubMed2005

Low-noise broadband light generation from optical fibers for use in high-resolution optical coherence tomography.

Broadband light generation from a single-mode optical fiber was developed for high-resolution optical coherence tomography (OCT). No noise amplification was observed for light broadened by self-phase modulation. The investigation showed that the intensity noise of light broadened by self-phase modulation in a single-mode optical fiber was much lower than that of continuum light from a microstructure fiber (MSF). The spectral width of a femtosecond input laser pulse was successfully broadened by a factor of 11, and a coherence length of 3.7 microm was achieved with this source. The application of light broadened by a single-mode optical fiber and MSF was compared for use in OCT imaging. The results showed that a single-mode fiber with a small core diameter is a useful way to generate low-noise, broadband light for high-resolution OCT imaging.

Algorithms↗

PubMed2005

Promoter hypermethylation and inactivation of O(6)-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines.

The purpose of this study was to characterize the role of DNA hypermethylation in the loss of expression of O(6)-methylguanine-DNA methyltransferase (MGMT) during the development of esophageal squamous cell carcinoma (ESCC) and to investigate its reactivation in cell lines. Samples were collected from Linzhou City of the Henan province in northern China, a high-risk area of this disease. The hypermethylation of promoter CpG islands of the MGMT gene was examined by methylation-specific PCR in ESCC and neighboring non-tumorous tissues, as well as in laser capture microdissected samples with normal epithelium, basal cell hyperplasia (BCH), and dysplasia (DYS). The MGMT mRNA and protein expression were determined with RT-PCR and immunohistochemistry, respectively. Five of 17 (29%) normal, 10 of 20 (50%) BCH, 8 of 12 (67%) DYS, and 13 of 18 (72%) ESCC samples had DNA hypermethylation in the MGMT promoter region, showing a gradual increase with the progression of carcinogenesis. The frequency of the loss of MGMT mRNA and protein expression progressively decreased from normal to BCH, DYS, and ESCC, and it was highly correlated with MGMT promoter hypermethylation according to Fisher's exact tests. When each individual sample was considered, good concordance between DNA hypermethylation and the loss of expression of MGMT was also observed. In samples from the same patient, if hypermethylation was detected in earlier lesions, it was usually observed in more severe lesions. In the ESCC cell line KYSE 510, treatment with a DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine partially reversed the CpG hypermethylation status and restored mRNA expression of the MGMT gene. Similar reactivation of MGMT gene by dietary polyphenols, (-)-epigallocatechin-3-gallate and genistein, has also been observed. The results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing in the development of ESCC, and this epigenetic event may be prevented or reversed by these polyphenols for the prevention of carcinogenesis.

Carcinoma, Squamous Cell↗

PubMed2004

Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that regulate various cell behaviors in cancer biology, via their basic function of degradation of proteins. Genetic variations in several MMP promoters may influence transcription and expression of MMPs. The aim of this study is to assess the effects of the two single nucleotide polymorphisms (SNPs), the guanine insertion polymorphism in the MMP1 promoter and the adenosine insertion polymorphism in the MMP3 promoter, on risk of the development and lymphatic metastasis of non-small cell lung carcinoma (NSCLC). The MMP1 and MMP3 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 243 NSCLC patients and 350 control subjects in North China. The overall genotype and allelotype distribution of both the variants in cancer patients and controls was not significantly different (all P values are above 0.05). However, stratification analysis showed that smoking individuals with the MMP3 5A allele had a >1.5-fold increased risk to develop NSCLC, compared with those harboring the 6A homozygous [the age and gender adjusted odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.04-2.70]. In addition, the frequency of the MMP3 5A homozygote in NSCLC patients with lymphatic metastasis was significantly higher than that in lymph node negative ones (5.7 versus 0%, P = 0.04). Moreover, the MMP 1G/5A haplotype significantly increased the risk of lymphatic metastasis (OR = 3.36, 95% CI = 1.42-7.94), compared with the 2G/6A haplotype. The present result suggested that the MMP3 promoter polymorphism may modify susceptibility to NSCLC, and the MMP 1G/5A haplotype may predicate the risk of lymphatic metastasis of this tumor.

Adult↗

PubMed2004

The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastasis in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma.

The matrix metalloproteinases (MMPs), a family of proteolytic enzymes that degrade different components of the extracellular matrix, play important roles in tumor development and invasion. A single adenine insertion/deletion polymorphism (6A/5A) in the MMP3 promoter region causes transcriptional elevation. The aim of this study was to assess the effects of this single nucleotide polymorphism (SNP) on the development and clinical staging of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). The MMP3 SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 417 cancer patients (234 ESCC and 183 GCA) and 350 controls in north China. The overall distribution of the MMP3 SNP in ESCC and GCA patients was not significantly different from that in healthy controls. However, smoking individuals with the 5A/5A or 5A/6A genotype were significantly more common in ESCC patients than in controls (37.5 versus 23.3%, xi(2) = 5.13, P = 0.02). Thus, smokers with at least one 5A allele had a significantly increased risk of ESCC, compared with 6A homozygotes (age and sex adjusted OR = 1.95, 95% CI = 1.08-3.53). The significant difference in the SNP distribution between ESCC patients, GCA patients and controls was not observed when stratified by family history of upper gastrointestinal cancer. In addition, the frequency of the 5A/5A + 5A/6A genotypes in ESCC patients with and without lymphatic metastasis was significantly different (45.8 versus 27.8%, xi(2) = 4.56, P = 0.03). Therefore, patients with at least one 5A allele were significantly more prone to lymphatic metastasis of ESCC. In contrast, no significant difference in the SNP distribution between patients with and without lymphatic metastasis was observed in GCA. The present study suggests that the MMP3 promoter SNP might be associated with a risk of development and lymphatic metastasis in ESCC but not in GCA.

Adenocarcinoma↗

PubMed2004

Second-harmonic optical coherence tomography.

Second-harmonic optical coherence tomography, which uses coherence gating of second-order nonlinear optical responses of biological tissues for imaging, is described and demonstrated. Femtosecond laser pulses were used to excite second-harmonic waves from collagen harvested from rat tail tendon and a reference non-linear crystal. Second-harmonic interference fringe signals were detected and used for image construction. Because of the strong dependence of second-harmonic generation on molecular and tissue structures, this technique imparts contrast and resolution enhancement to conventional optical coherence tomography.

Animals↗

PubMed2004

[Clinical analysis of 15 cases of Paget's disease of the scrotum].

OBJECTIVE: To study the clinicopathologic features and treatment of Paget's disease of the scrotum. METHODS: Fifteen cases of Paget's disease of the scrotum, pathologically diagnosed and successfully treated by surgery from 1987 to 2003, were studied retrospectively. RESULTS: Typical pathological features were observed in all the patients. Thirteen cases were followed up for 0. 5 approximately 13 years, of whom 1 case relapsed within 3 years, 2 died of metastasis after 2 years, and 3 died of cardiovascular diseases, with no recurrence in the others. CONCLUSION: Early biopsy and extensive excision of the scrotal lesion is the first choice of treatment for Paget's disease, with good operative effect and satisfactory prognosis. A 2nd operation could be considered for patients of local relapse.

Aged↗

PubMed2003

Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines.

Hypermethylation of CpG islands in the promoter regions is an important mechanism to silence the expression of many important genes in cancer. The hypermethylation status is passed to the daughter cells through the methylation of the newly synthesized DNA strand by 5-cytosine DNA methyltransferase (DNMT). We report herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells. With nuclear extracts as the enzyme source and polydeoxyinosine-deoxycytosine as the substrate, EGCG dose-dependently inhibited DNMT activity, showing competitive inhibition with a K(i) of 6.89 microM. Studies with structural analogues of EGCG suggest the importance of D and B ring structures in the inhibitory activity. Molecular modeling studies also support this conclusion, and suggest that EGCG can form hydrogen bonds with Pro(1223), Glu(1265), Cys(1225), Ser(1229), and Arg(1309) in the catalytic pocket of DNMT. Treatment of human esophageal cancer KYSE 510 cells with 5-50 microM of EGCG for 12-144 h caused a concentration- and time-dependent reversal of hypermethylation of p16(INK4a), retinoic acid receptor beta (RARbeta), O(6)-methylguanine methyltransferase (MGMT), and human mutL homologue 1 (hMLH1) genes as determined by the appearance of the unmethylation-specific bands in PCR. This was accompanied by the expression of mRNA of these genes as determined by reverse transcription-PCR. The re-expression of RARbeta and hMLH1 proteins by EGCG was demonstrated by Western blot. Reactivation of some methylation-silenced genes by EGCG was also demonstrated in human colon cancer HT-29 cells, esophageal cancer KYSE 150 cells, and prostate cancer PC3 cells. The results demonstrate for the first time the inhibition of DNA methylation by a commonly consumed dietary constituent and suggest the potential use of EGCG for the prevention or reversal of related gene-silencing in the prevention of carcinogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Hypermethylation-associated inactivation of retinoic acid receptor beta in human esophageal squamous cell carcinoma.

PURPOSE: The purpose of this study was to investigate the mechanism of altered retinoic acid receptor beta (RARbeta) expression during esophageal squamous carcinogenesis. EXPERIMENTAL DESIGN: Samples were collected from Linzhou, China. The hypermethylation of CpG islands in the promoter region of the RARbeta gene was examined by methylation-specific PCR in human esophageal squamous cell carcinoma (ESCC) samples, as well as in neighboring tissues with normal epithelium, basal cell hyperplasia, and dysplasia. RARbeta mRNA expression was determined by in situ hybridization. The DNA methyltransferase inhibitor 2'-deoxy-5-azacytidine was used to treat the ESCC cell line, and the DNA hypermethylation status and mRNA expression level were examined. RESULTS: Two of 17 (12%) normal, 9 of 21 basal cell hyperplasia (43%), 7 of 12 dysplasia (58%), and 14 of 20 ESCC (70%) samples had hypermethylation of the RARbeta promoter region. The loss of RARbeta mRNA expression was highly concordant with RARbeta promoter CpG island hypermethylation when individual samples were considered in the correlation analysis. Good statistical correlation between hypermethylation and loss of RARbeta expression was revealed. Frequencies of hypermethylation appeared to increase with the progression of carcinogenesis. In samples from the same patients, if hypermethylation was detected in earlier lesions, it was usually observed in more severe lesions. In the ESCC cell line KYSE 510, 2'-deoxy-5-azacytidine partially reversed CpG island hypermethylation and restored RARbeta mRNA expression. CONCLUSIONS: The results suggest that hypermethylation of RARbeta promoter region is an important mechanism for RARbeta gene silencing in esophageal squamous carcinogenesis.

Carcinoma, Squamous Cell↗

PubMed2003

Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber.

We have developed an ultrahigh-resolution optical coherence tomographic system in which broadband continuum generation from a photonic crystal fiber is used to produce high longitudinal resolution. Longitudinal resolution of 1.3-microm has been achieved in a biological tissue by use of continuum light from 800 to 1400 nm. The system employed a dynamic-focusing tracking method to maintain high lateral resolution over a large imaging depth. Subcellular imaging is demonstrated.

Animals↗