Publications by authors named "Yingfang Li"

16 Publications

  • Page 1 of 1

Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus.

Biochem Biophys Res Commun 2021 Aug 12;567:1-8. Epub 2021 Jun 12.

Department of Virology II, National Institute of Infectious Diseases, 162-8640, Tokyo, Japan. Electronic address:

Natural product-derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compounds threo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted from Crataegus cuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds #106 and #110 specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound #106 also inhibited the replication and production of hepatitis A virus. Our findings suggest that C. cuneate is a new source for novel anti-hepatitis virus drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.06.022DOI Listing
August 2021

Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: Results from a randomized double-blinded placebo-controlled interventional study.

J Cosmet Dermatol 2021 May 31. Epub 2021 May 31.

Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, Tongji University School of medicine, Shanghai, China.

Background: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks.

Aims: In this communication, we aim to demonstrate the effectiveness of a novel cannabidiol (CBD) and aspartame formulation, JW-100, in relieving signs and symptoms of AD.

Patients/methods: We conducted a double-blinded placebo-controlled interventional study randomizing patients to one of three treatment groups: JW-100 (CBD plus aspartame), CBD only, or placebo topical formulations. The Investigator's Static Global Assessment (ISGA) score was used to document any changes in AD resulting from the applied interventions at 14 days.

Results: Fifty-seven patients completed the trial and were included in the final analysis. The ISGA score of the patients at baseline was 2.56, 2.24, and 2.24, for the JW-100, CBD, and placebo groups, respectively. After two weeks of treatment, the ISGA score reduced by 1.28, 0.81, and 0.71, for the JW-100, CBD, and placebo groups, respectively. The JW-100 cohorts demonstrated statistically significant ISGA score reduction (p = 0.042). 50% of patients in the JW-100 group achieved ISGA score of clear or almost clear (0 or 1) with at least a 2-grade improvement from baseline after treatment (p = 0.028). Only 20% and 15% of patients in the CBD only and placebo groups reported ISGA score of clear or almost clear (0 or 1).

Conclusions: JW-100, a novel topical formulation containing CBD and aspartame, was demonstrated to produce statistically significant improvements in AD following 14 days of topical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocd.14263DOI Listing
May 2021

Three-dimensional spatiotemporal evolution of wildfire-induced smoke aerosols: A case study from Liangshan, Southwest China.

Sci Total Environ 2021 Mar 17;762:144586. Epub 2020 Dec 17.

Plateau Atmospheric and Environment Key Laboratory of Sichuan Province, College of Atmosphere Sciences, Chengdu University of Information Technology, Chengdu 610225, China.

Carbonaceous aerosols and gaseous pollutants emitted from wildfires play a crucial role in both the global climate system and regional air quality. Here, using multisource satellite and ground-based observations combined with reanalysis data, we investigate the three-dimensional evolution of biomass-burning emissions from a forest wildfire event in Liangshan, Southwest China, which occurred from 29 March to 1 April 2020. The meteorological field analysis showed that the negative anomaly of relative humidity and precipitation, as well as the positive anomaly of near-surface wind speed, created favourable conditions for the occurrence and spread of this wildfire event. During the fire, satellite observations suggested a maximum fire radiation power of over 100 MW. In addition, there were significant short-term effects of fire activity on regional air quality, with downwind surface PM concentrations at the Xichang site reaching a maximum of approximately 470 μg·m on March 31. Driven by a southwesterly airflow, large amounts of smoke aerosols were transported rapidly to downstream areas, significantly deteriorating air quality, with the maximum value of the aerosol optical depth (AOD) exceeding 2. Moreover, the quantitative evaluation based on Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) reanalysis showed that the instantaneous maximum values of the column mass concentration of black carbon (BC) and organic carbon (OC) reached 9.8 g·m and 1.8 g·m during the fire respectively. Further analysis suggested that the interaction between the lower and upper atmosphere constrained the smoke aerosols to altitudes below approximately 5 km, which was also supported by the vertical distribution of elevated smoke aerosols observed by the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.144586DOI Listing
March 2021

CircRNA-1806 Decreases T Cell Apoptosis and Prolongs Survival of Mice After Cryptococcal Infection by Sponging miRNA-126.

Front Microbiol 2020 13;11:596440. Epub 2020 Nov 13.

Department of Dermatology and Venereology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

CircRNAs are a recently well-known regulator that mediates a variety of biological processes. Cryptococcus neoformans is an environmental fungal pathogen that can cause fatal cryptococcal meningitis in immunocompromised individuals. However, the involvement of circRNA in cryptococcal infection remains unclear. In this study, high-throughput microarray was performed to identify the circRNA expression profile in cryptococcal meningitis patients. Circ_0001806 was significantly decreased in cryptococcal meningitis individuals. Then the effects of circ_0001806 and its interaction with miRNAs were explored and . The knock-down of circ_0001806 led to higher fungal infection and shorter survival in an experimental murine cryptococcosis model. Transcriptome analysis showed that decreased circ_0001806 regulated pathways related to the host antimicrobe response in T cells. Furthermore, experiments showed that circ_0001806 positively modulates ADM level, decreasing cell apoptosis and G1S arrest in T cells. Finally, we found circ_0001806 exerted its effects by sponging miRNA-126 in T cells. Taken together, our results reveal the role of circRNA-1806/miRNA-126 in the regulation of cell cycle and apoptosis in cryptococcal infection and can provide a new insights of the pathogenesis of cryptococcal infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.596440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691421PMC
November 2020

Genotypic diversity and antifungal susceptibility of environmental isolates of Cryptococcus neoformans from the Yangtze River Delta region of East China.

Med Mycol 2021 Jul;59(7):653-663

Department of Dermatology, Shanghai Key Laboratory of Medical Mycology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Although cryptococcosis is widely recognized as infection by Cryptococcus neoformans sensu lato from environmental sources, information concerning the characteristics of environmental isolates of C. neoformans s. l. and how they are related to clinical isolates is very limited, especially in East China. In this study, 61 environmental isolates of C. neoformans were recovered from pigeon (Columba livia) droppings from the Yangtze River Delta region of East China. These isolates were genotyped using the ISHAM-MLST consensus scheme and their antifungal drug susceptibilities were determined following the CLSI M27-A3 guidelines. The 61 isolates were found belonging to 13 sequence types (STs), including several novel STs such as ST254 and ST194. The dominant ST in this environmental sample was ST31, different from that of clinical strains (ST5) in this region. Azole-resistance, such as fluconazole (FLU)-resistance, was observed among our environmental C. neoformans isolates. The findings of this study expand our understanding of ecological niches, population genetic diversity, and azole-resistance characteristics of the yeast in East China. Our research lays the foundation for further comparative analysis the potential mechanisms for the observed differences between environmental and clinical populations of C. neoformans in China.

Lay Summary: Cryptococcosis is widely recognized as infection by Cryptococcus neoformans sensu lato from environmental sources. However, there is currently limited information about the genetic diversity and antifungal susceptibility of environmental C. neoformans s. l. isolates, including how they may differ from clinical samples. In this study, we collected 61 environmental C. neoformans isolates from domestic pigeon droppings from the Yangtze River Delta region of East China. These isolates were genotyped using multi-locus sequencing. We found a high genotypic diversity in this population of C. neoformans, with several novel genotypes and a distribution of genotypes different from that of clinical strains in this region. Azole-resistance, such as fluconazole (FLU)-resistance, was observed among our environmental C. neoformans isolates. The findings of this study expand our understanding of ecological niches, genetic diversity, and azole-resistance characteristics of the yeast in East China. Our research lays the foundation for phylogenomic analysis investigating why and how disparate population structures of C. neoformans isolates formed between environmental and clinical sources in the region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/mmy/myaa096DOI Listing
July 2021

MCPIP1 reduces HBV-RNA by targeting its epsilon structure.

Sci Rep 2020 11 27;10(1):20763. Epub 2020 Nov 27.

Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan.

Hepatitis B virus (HBV) is the major causative factor of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. We previously demonstrated that a proinflammatory cytokine IL-1β reduced the level of HBV RNA. However, the mechanism underlying IL-1β-mediated viral RNA reduction remains incompletely understood. In this study, we report that immune regulator Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) can reduce HBV RNA in hepatocytes. MCPIP1 expression level was higher in the liver tissue of HBV-infected patients and mice. Overexpression of MCPIP1 decreased HBV RNA, whereas ablating MCPIP1 in vitro enhanced HBV production. The domains responsible for RNase activity or oligomerization, were required for MCPIP1-mediated viral RNA reduction. The epsilon structure of HBV RNA was important for its antiviral activity and cleaved by MCPIP1 in the cell-free system. Lastly, knocking out MCPIP1 attenuated the anti-HBV effect of IL-1β, suggesting that MCPIP1 is required for IL-1β-mediated HBV RNA reduction. Overall, these results suggest that MCPIP1 may be involved in the antiviral effect downstream of IL-1β.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-77166-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699622PMC
November 2020

EBV-LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer.

Cancer Med 2020 10 20;9(20):7663-7671. Epub 2020 Aug 20.

Division of Otorhinolaryngology and Head and Neck Surgery, Kanazawa University, Kanazawa, Japan.

An Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a principal oncogene that plays a pivotal role in EBV-associated malignant tumors including nasopharyngeal cancer (NPC). Recent genomic landscape studies revealed that NPC also contained many genomic mutations, suggesting the role of LMP1 as a driver gene for the induction of these genomic mutations. Nonetheless, its exact mechanism has not been investigated. In this study, we report that LMP1 alters the expression profile of APOBEC3s(A3s), host deaminases that introduce consecutive C-to-U mutations (hypermutation). In vitro, LMP1 induces APOBEC3B (A3B) and 3F(A3F), in a nasopharyngeal cell line, AdAH. Overexpression of LMP1, A3B, or A3F induces mtDNA hypermutation, which is also detectable from NPC specimens. Expression of LMP1 and A3B in NPC was correlated with neck metastasis. These results provide evidence as to which LMP1 induces A3s and mtDNA hypermutation, and how LMP1 facilitates metastasis is also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571841PMC
October 2020

Different antiviral activities of natural APOBEC3C, APOBEC3G, and APOBEC3H variants against hepatitis B virus.

Biochem Biophys Res Commun 2019 10 7;518(1):26-31. Epub 2019 Aug 7.

Department of Molecular Genetics, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan. Electronic address:

Some APOBEC3 family members have antiviral activity against retroviruses and DNA viruses. Hepatitis B virus (HBV) is a DNA virus that is the major causative factor of severe liver diseases such as cirrhosis and hepatocellular carcinoma. To determine whether APOBEC3 variants in humans have different anti-HBV activities, we evaluated natural variants of APOBEC3C, APOBEC3G, and APOBEC3H using an HBV-replicating cell culture model. Our data demonstrate that the APOBEC3C variant S188I had increased restriction activity and hypermutation frequency against HBV DNA. In contrast, the APOBEC3G variant H186R did not alter the anti-HBV and hypermutation activities. Among APOBEC3H polymorphisms (hap I-VII) and splicing variants (SV-200, SV-183, SV-182, and SV-154), hap II SV-183 showed the strongest restriction activity. These data suggest that the genetic variations in APOBEC3 genes may affect the efficiency of HBV elimination in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2019.08.003DOI Listing
October 2019

Cryptococcosis in patients with diabetes mellitus II in mainland China: 1993-2015.

Mycoses 2017 Nov 30;60(11):706-713. Epub 2017 Aug 30.

Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/myc.12645DOI Listing
November 2017

Molecular characterization of AID-mediated reduction of hepatitis B virus transcripts.

Virology 2017 10 2;510:281-288. Epub 2017 Aug 2.

Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. Electronic address:

Hepatitis B virus (HBV) is the major cause of liver cirrhosis and hepatocellular carcinoma. After entering a hepatocyte, HBV forms a nuclear viral episome and produces pregenomic (pg) RNA with a stem-loop structure called an epsilon, which acts to signal encapsidation. We previously demonstrated that TGF-β upregulates activation-induced cytidine deaminase (AID) expression in hepatocytes, which in turn downregulates HBV transcripts by recruiting the RNA exosome complex. The molecular mechanism underlying AID-mediated HBV RNA reduction remains largely unclear. Here we used a pgRNA reporter system having a reporter gene within pgRNA to identify sis- and trans-acting elements in AID-mediated HBV RNA reduction. We found that the epsilon RNA and C-terminus of AID are required for AID-mediated HBV RNA reduction. Importantly, this reduction was reproduced in a hydrodynamic HBV transfection mouse model. The molecular mechanism of AID-mediated HBV RNA reduction is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2017.07.035DOI Listing
October 2017

Cryptococcosis in Patients with Nephrotic Syndrome: A Pooled Analysis of Cases.

Mycopathologia 2017 Jun 4;182(5-6):517-525. Epub 2017 Jan 4.

Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

Cryptococcosis is an infection that may be lethal in patients with nephrotic syndrome (NS). However, there is relatively limited epidemiological and clinical data about cryptococcosis in NS patients. We performed a pooled analysis to systemically summarize the epidemiology, risk factors, clinical and laboratory characteristics, treatments and outcomes of cryptococcosis in NS patients. Using data pooled from our hospital and studies identified via searches of three literature databases, 17 cases were identified for inclusion in this analysis. The prevalence of cryptococcosis in NS was 0.3%, with a higher rate in more recent years. Most patients were Asian (94%) and from upper-middle to high-income countries (76%). The median time interval from NS diagnosis to cryptococcosis diagnosis among the cryptococcosis patients was 16 months, and 46% of the identified cryptococcal infections were diagnosed within the first year of NS diagnosis. Cutaneous cryptococcosis was frequently diagnosed among the included patients (35%), 58% received an erroneous diagnosis and inappropriate treatment, 90% of whom had a cryptococcal infection mistaken for a bacterial infection. The mortality rate was 35%. Standard therapeutic strategies should be emphasized for both antifungal treatment and renal disease control. Further studies conducted in various medical centers are warranted to confirm our conclusions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11046-016-0101-9DOI Listing
June 2017

Methylation of S100A8 is a promising diagnosis and prognostic marker in hepatocellular carcinoma.

Oncotarget 2016 Aug;7(35):56798-56810

Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, China.

The abnormality of DNA methylation is one of the major epigenetic alterations in the human hepatocellular carcinoma (HCC). We have assessed the global genomic DNA methylation profiles in human HCC patients by using the Infinium Human Methylation27 BeadChip. A CpG loci of S100A8 was found to be significantly hypomethylated in HCC.Pooled meta-analysis of five validation public datasets demonstrated its methylation level was significantly lower for HCC compared to paired adjacent normal tissues. Quantitative pyrosequencing analysis also showed that the S100A8 methylation level was decreased in cancer tissues (31.90%±13.31%) than that in the paired adjacent normal tissues (65.33%±3.64%, p<0.01). The area under the ROC curve (AUC) value was 0.950 (p<0.01). Kaplan-Meier survival curves revealed that hypomethylation of S100A8 was associated with shortened overall survival (OS) and progression-free survival (PFS) (log rank p<0.05). Multivariate Cox proportional hazards model also indicated significantly shorter OS (HR, 1.709; 95 % CI, 1.127-2.591) and PFS (HR, 1.767; 95 % CI, 1.168-2.974) were observed in the low-methylation-level group compared to the high-methylation-level group. Furthermore, S100A8 overexpression in Huh7 and MHCC-97H hepatoma cell lines led to increased cell proliferation, migration, invasion, and tumor growth. These findings suggested S100A8 methylation to be served as potential diagnosis and prognosis marker for HCC. S100A8 also may play as a tumor promoter in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.10792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302953PMC
August 2016

Renoprotective effect of atorvastatin on STZ-diabetic rats through attenuating kidney-associated dysmetabolism.

Eur J Pharmacol 2014 Oct 5;740:9-14. Epub 2014 Jul 5.

Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin 541001, China. Electronic address:

Atorvastatin (AT) has been alternatively used for managing diabetic complications in clinic. However, AT-related therapeutic potentiality remains relatively unexplored, especially in diabetic nephropathy. This study aimed to investigate the underlying potentiality that AT exerted on anti-diabetic nephropathy role against streptozotocin (STZ)-induced kidney injury in rats. STZ-diabetic rats were intragastrically administered with AT (10, 20 mg/kg/d) for consecutive 8 weeks. The effects of AT on body weight, levels of blood glucose, lipometabolism, redox state, cellular metabolism, regulator factor and kidney morphological changes were monitored by routine measurement, biochemistry assay, PT-PCR analysis, ultrastructural and pathological observations, respectively. Compared with the diabetic nephropathy rats, AT elevated the body weight of diabetic nephropathy rats (P<0.01), effectively reduced the blood glucose level (P<0.01), increased the levels of insulin and high-density lipoprotein cholesterol (HDL-C) in plasma (P<0.01), and decreased the 24 h urine protein content and serum concentrations of low-density lipoprotein cholesterol (LDL-C) (P<0.01). Meanwhile, increase in kidney tissue, the intrarenal activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced, while the malonaldehyde (MDA) content was reduced (P<0.01). In addition, the expression of transforming growth factor beta 1 (TGF-β1) mRNA in kidney tissue was notably down-regulated (P<0.01). Furthermore, AT contributed to alleviating STZ-induced nephritic damages in rats. These results demonstrate that atorvastatin exerts the effective protective role against kidney injuries of STZ-induced diabetic nephropathy rat, which the underlying mechanisms are associated with ameliorating glyco, lipometabolism, enhancing antioxidant ability, and mitigating renal damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2014.06.055DOI Listing
October 2014

A retrospective study of treatment efficacy of 65 children with ametroic amblyopia.

Eye Sci 2012 Jun;27(2):85-8

Shaoguan Hygienic Hospital of Women and Children, China.

Purpose: To investigate relationship between treatment efficacy and the severity of ametropic amblyopia, the type of anisometropia and patient age.

Methods: A total of 65 children with ametropic amblyopia undergoing clinical treatment in the ophthalmology department of Shaoguan Hygienic Hospital of Women and Children between June 2005 and November 2011 were enrolled in this study. The treatment efficacy for those subjects with different severities of ametropic amblyopia, types of anisometropia and ages was recorded.

Results: The near-recovery/recovery rate, improvement rate and ineffectiveness rate were 70.8%, 16.9% and 12.3%, respectively. The recovery rates in mild-, moderate- and severe amblyopia groups were 97.1%, 61.1% and 8.3% respectively (P<0.05). The recovery rate for patients with hyperopic-, astigmatic- and myopic anisometropia were 75.8%, 78.3% and 33.3% respectively. The recovery rates did not differ between hyperopic- and astigmatic- anisometropia children (P>0.05), whereas a statistically significant difference was noted between myopic children compared with their hyperopic and myopic-anisometropia counterparts (all P<0.05). The recovery rate for patients aged 3 to 6 years was 86.8% and 48.1% for those aged between 7 and 10 years (P<0.05).

Conclusion: The treatment efficacy in ametropic amblyopia is associated with the severity of amblyopia, type of anisometropia and patient's age. Older patients with more severe amblyopia had poorer treatment efficacy. The efficacy in patients with hyperopic and astigmatic anisometropia was better than that for myopic anisometropia subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3969/j.issn.1000-4432.2012.02.007DOI Listing
June 2012

Epstein-Barr virus infected lymphoepithelial carcinomas of the salivary gland in the Russia-Asia area: a clinicopathologic study of 160 cases.

Arkh Patol 2003 Mar-Apr;65(2):35-9

Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

In order to determine the prevalence of the Epstein-Barr virus (EBV) infection in salivary gland lymphoepithelial carcinomas (LEC), we have collected 160 cases from Asian countries and Russia. All the cases examined by PCR for EBV DNA BamHI fragment and in-situ hybridization for EBER-1, EBV encoded small RNA, showed positivity for EBV infection in LEC cells, while no positive signals were found in any other salivary neoplasm examined. The incidence of LEC was highest in Guanzhou, followed by Shanghai and Chengdu and lowest in the northern parts of China, Seoul, Niigata, and Moscow. The mean age of the patients with LEC was 43.9 years with no sex predilection. The Chinese patients were of the Han race, only including minor races. There were ninety-five cases found with LEC in the parotid gland (75%), 20 in the submandibular gland (5%), and 28 in the minor salivary gland (20%). Histologically, the LECs were classified into two types: small nest type and large nest type. The latter type consisted of large-sized tumor cell nests and dense lymphocytic stromata and more frequently occurred in the minor salivary gland. The former consisted of small-sized tumor cell nests with fibrous and lymphocyte-depleted stromata, which were more frequently found in the parotid gland. The results indicated that EBV infection and certain geographic factors play important roles in the pathogenesis of the salivary LEC.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2004

Mutational events in LMP1 gene of Epstein-Barr virus in salivary gland lymphoepithelial carcinomas.

Int J Cancer 2003 Jul;105(5):654-60

Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan.

It is still unknown what kinds of roles Epstein-Barr virus (EBV) infection that are highly specific to salivary gland lymphoepithelial carcinomas (LECs) play in their tumorigenesis. To clarify the significance of EBV in LECs, we paid particular attention to the LMP1 gene, which is responsible for triggering several pathways for activating transcription factors. Sixty-one cases of EBV positive LECs confirmed by PCR and in-situ hybridization were collected from various areas of the world and studied immunohistochemically for latent membrane protein-1. Furthermore, PCR for the LMP1 carboxyl (C)-terminus region was performed, and the PCR products were sequenced for detection of other mutational events. LMP1 gene products were immunohistochemically demonstrated in 51% of the cases, while PCR amplification of the LMP1 gene was successful in 41 cases (67%). Among them, a 30 bp deletion in the C-terminus of the LMP1 gene, which had been shown to be characteristic to EBV in Chinese nasopharyngeal carcinomas, was found in 20 cases (32%). Most of them were from Guangzhou, Chengdu and Taiwan, while most of the cases from Shanghai and other areas exhibited no 30 bp deletion. In addition, several point mutations including codon 338 of LMP1 were commonly shared by the cases with or without the 30 bp deletion. These results indicate that there are 2 major genomic variations of EBV infecting salivary gland LECs. The frequent mutational events in the C-terminus in addition to the 30 bp deletion also seem to be critical for the pathogenesis because such mutational events may possibly promote cellular proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.11100DOI Listing
July 2003
-->