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1.
Hepatol Int ; 14(1): 96-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31832976

RESUMO

BACKGROUND: The diagnostic and prognostic values of glypican3 (GPC3) and glutamine synthetase (GS) proteins in hepatocellular carcinoma (HCC) have been reported, but their specificity and sensitivity remain low. Here, we applied RNAscope to improve HCC early pathological and differential diagnosis by estimating GPC3 and GS mRNAs. METHODS: We performed RNAscope and immunohistochemistry (IHC) to detect GPC3 and GS biomarkers on the tissue sections of 194 cases, including high- and low-grade liver dysplastic nodules; highly, moderately, and poorly differentiated HCCs; intrahepatic cholangiocarcinomas (ICCs); metastatic HCC; and carcinomas from other organs. RESULTS: The results showed that all the cases that were negative for GPC3 by RNAscope were also negative for this protein by IHC. The use of RNAscope assay improved the GPC3 and GS specificity and sensitivity by 20-30%. Hence, HCC shows early recognition and upgrades the metastatic HCC differentiation by 23% compared with IHC (p = 0.0001, 0.0064). Meanwhile, all liver cirrhosis, cholangiocytes and non-HCC samples were negative for GPC3 and GS except lymphocytes in lymphomas, and 2 (8.3%) out of the 24 ICC samples but not in the cancer cells. CONCLUSION: RNAscope for GPC3 and GS panel was highly specific and sensitive for the pathological identification of dysplastic nodules, early stages of HCCs, and would differentiate them from HCCs and metastatic tumors compared with IHC.

2.
Ann Transl Med ; 7(18): 488, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31700924

RESUMO

Background: Psoriasis is a common chronic inflammatory skin disease with high recurrence rates and increasing incidence. Patients require long-term medication to reduce symptoms and prevent disease progression. Therefore, the development of treatments with high efficiency and low rate of adverse events is of utmost importance. Traditional Chinese medicine (TCM) plays an outstanding role in reducing disease symptoms and improving quality of life. The aim of this trial is to clarify the treatment efficacy, safety, and control of disease recurrence in patients with psoriasis with blood-stasis syndrome treated with Taodan granules (TDKL). Methods: This trial is a five-center, randomized, double-blind, placebo-controlled study planned to transpire between September 1, 2019, and December 31, 2021. A sample size of 216 participants (108 per group) with mild-to-moderate psoriasis will be randomly assigned to receive TDKL or placebo twice per day, 7 days per week, for 8 weeks. The study duration will be 17 weeks, including a 1-week screening period, 8 weeks of intervention, and another 8 weeks of follow-up. The primary outcomes are improvement in the Psoriasis Area and Severity Index score and recurrence rate after 8 weeks of treatment. Secondary outcomes include body surface area affected and the scores for the Physician Global Assessment, Dermatology Life Quality Index, pain-related quality of life, pain on the visual analogue scale, and TCM syndromes. The number, nature, and severity of adverse events will be carefully recorded. Discussion: The study results will help clarify the safety and efficacy of TDKL as treatment for psoriasis with respect to both disease regression and recurrence rate. We expect that this study will provide high-quality evidence with important public health implications that may alter the approach to psoriasis management in China. Trial registration: The trial has been registered at ClinicalTrials.gov (ID: NCT03942198).

3.
Chin Med J (Engl) ; 132(11): 1305-1313, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31009392

RESUMO

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL. METHODS: We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients' overall survival (OS). RESULTS: Of the 86 patients, 71 (82.6%) experienced invasion of AS, 22 (25.6%) of soft tissue, and 26 (30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ = 4.105, P = 0.043) or brain involvement (Log rank χ = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ = 10.390, P = 0.001) or bones (Log rank χ = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. CONCLUSIONS: Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.


Assuntos
Linfoma Extranodal de Células T-NK/patologia , Adolescente , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Músculos Faciais/diagnóstico por imagem , Músculos Faciais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Células Matadoras Naturais/patologia , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Adulto Jovem
4.
Crit Rev Oncol Hematol ; 135: 30-38, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30819444

RESUMO

Epstein-Barr virus (EBV) is believed to be a pathogen causing a number of human cancers, but the pathogenic mechanisms remain unclear. An increasing number of studies have indicated that EBV-encoded microRNAs (EBV miRNAs) are expressed in a latency type- and tumor type-dependent manner, playing important roles in the development and progression of EBV-associated tumors. By targeting one or more genes of the virus and the host, EBV miRNAs are responsible for the deregulation of a variety of viral and host cell biological processes, including viral replication, latency maintenance, immune evasion, cell apoptosis and metabolism, and tumor proliferation and metastasis. In addition, some EBV miRNAs can be used as excellent diagnostic, prognostic and treatment efficacy predictive biomarkers for EBV-associated tumors. More importantly, EBV miRNA-targeting therapeutics have emerged and have been developing rapidly, which may open a new era in the treatment of EBV-associated tumors in the near future.


Assuntos
Infecções por Vírus Epstein-Barr/genética , MicroRNAs/genética , Neoplasias/patologia , Neoplasias/virologia , Infecções Tumorais por Vírus/genética , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Humanos , RNA Viral/genética , Evasão Tumoral/genética , Infecções Tumorais por Vírus/complicações , Latência Viral/genética , Replicação Viral/genética
5.
Int J Ophthalmol ; 12(2): 275-279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809484

RESUMO

AIM: To evaluate the relationship between contrast sensitivity (CS) and corneal shape following overnight orthokeratology (OK). METHODS: We conducted a retrospective clinical study of 80 lens-wearing myopia patients, all of whom had undergone OK and had been evaluated by Orbscan II topography. We measured the surface irregularity index (SIRI) of corneal topography at 3 and 5 mm, the size of the flattened central corneal curvature of OK lens (zone A), the size of the cornea altered by OK lens (zone B), the size of the pupillary area at the corneal level (zone C), the area of crossover between zones A and C (zone AC), the area of crossover between zones B and C (BC), the ratio of BC to B (BC/B), and the ratio of AC to C (AC/C). CS was evaluated using the CSV-1000 with spatial frequencies of 3, 6, 12, and 18 cycles/degree (CPD). RESULTS: Multiple correlation analyses indicated significant negative correlations between CS, zone C, BC/B, and 3-mm SIRI (all P<0.01). There were no significant differences between CS, zone B, AC/A, or 5-mm SIRI (P=0.60, 0.94 and 0.11, respectively). Zone C was negatively correlated with 3, 6, 12, and 18 CPD. 5-mm SIRI were negatively correlated with 6, 12, and 18 CPD. BC/C was negatively correlated with 6 and 18 CPD. AC/C was positively correlated with 3 CPD. CONCLUSION: Zone C, 3-mm SIRI and BC/B affect the CS following overnight OK.

6.
Virology ; 529: 144-151, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30710798

RESUMO

Circular RNAs (circRNAs) are a novel class of non-coding RNA molecules in eukaryotic organisms that have potentially important roles in gene regulation. Nevertheless, whether viruses can encode circRNA is still uncertain. To examine whether large genome DNA viruses can generate circRNA during the infection of human cells, we performed RNA sequencing of ribosomal RNA-depleted total RNA from Epstein-Barr virus (EBV)-infected cell lines, including SNU-719, AGS-EBV, C666-1 and Akata. We identified an EBV-encoded circRNA, ebv_circ_RPMS1, that consists of the head-to-tail splicing of exons 2-4 from the RPMS1 gene. Furthermore, we demonstrated that ebv_circ_RPMS1 was localized in both cytoplasm and nuclei. Given that circRNAs shape gene expression by titrating microRNAs, regulating transcription and/or interfering with splicing, we identified a novel viral regulator of host and/or viral gene expression.


Assuntos
Herpesvirus Humano 4/genética , RNA não Traduzido/genética , RNA Viral/genética , Animais , Linhagem Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Experimentais/virologia
7.
Hum Pathol ; 85: 82-91, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30448221

RESUMO

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously inflammatory infiltration compared with EBV-negative gastric carcinoma. To date, the local immune status in EBVaGC and its relationship with patient prognosis and apoptosis of tumor cells are largely unknown. In this study, we evaluated the density of different types of tumor-infiltrating lymphocytes (TILs) in 53 EBVaGCs and 67 EBV-negative gastric carcinomas and analyzed its relationship with patient outcomes and apoptosis of tumor cells in EBVaGC. The average number of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, CD56+ natural killer cells, Fascin+ dendritic cells (DCs), and FoxP3+ Tregs and the average proportions of Ki-67, interleukin 1ß, granzyme B, interferon γ, and interleukin 10 in TILs were higher in EBVaGC, and CD8+ T cells were the predominant constituent cells of TILs in EBVaGC. Patients with higher numbers of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs survived longer in EBVaGC, and CD8+ T cells and Fascin+ DCs were independent prognostic factors for patient survival. Besides, CD8+ T cells were positively correlated with apoptotic index of tumor cells. However, the apoptosis of tumor cells was lower, and the expression of survivin and NF-κBp65 in tumor cells was up-regulated in EBVaGC. These findings suggested that CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs predict a better prognosis in EBVaGC; CD8+ T cells might through a nonapoptotic pathway eliminate tumor cells, thereby improving the patient prognosis.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Gástricas/imunologia , Apoptose , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4 , Humanos , Linfócitos do Interstício Tumoral/patologia , Linfócitos do Interstício Tumoral/virologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia , Taxa de Sobrevida
8.
Pathology ; 50(6): 613-621, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30149990

RESUMO

About 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV), which are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are usually accompanied by massive lymphocytes infiltration, among which CD8+ T cells are predominant. To date, the apoptosis of the infiltrating CD8+ T cells in EBVaGC has not been investigated. In the present study, we assessed the immunophenotype and apoptosis of tumour infiltrating lymphocytes (TILs) in both EBVaGC and EBV-negative gastric carcinoma (EBVnGC). We found that CD8+CCR7+ T lymphocytes were increased in EBVaGC compared to EBVnGC [60.53 ± 28.41/high power fields (HPF) vs 19.63 ± 15.97/HPF; p < 0.001]. Moreover, the apoptosis index of TILs was lower in EBVaGC than that in EBVnGC (1.34 ± 0.90 vs 5.94 ± 3.77; p < 0.001). Given that the CCL21-CCR7 axis is reported to be potentially involved in apoptosis, we examined the expression of CCL21 in both EBVaGC and EBVnGC. We found that CCL21 expression was higher in EBVaGC than in EBVnGC (p < 0.001). We also showed that the expression of CCL21 by EBVaGC cells protected CD8+CCR7+ T lymphocytes from apoptosis. Furthermore, the up-regulation of Bcl-2 contributed to the inhibition of apoptosis in CD8+CCR7+ T cells. Collectively, these findings suggest that expression of CCL21 by EBVaGC cells protects CD8+CCR7+ T lymphocytes from apoptosis via the mitochondria-mediated pathway. To our best knowledge, this is the first study to investigate the apoptosis of CD8+ T cells in EBVaGC.


Assuntos
Adenocarcinoma , Linfócitos T CD8-Positivos/imunologia , Quimiocina CCL21/biossíntese , Infecções por Vírus Epstein-Barr/complicações , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Gástricas , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Apoptose/imunologia , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia
9.
Zhonghua Bing Li Xue Za Zhi ; 42(9): 580-3, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24314241

RESUMO

OBJECTIVE: To use array-based comparative genomic hybridization (aCGH) technology to study the molecular cytogenetic abnormalities of anaplastic large cell lymphoma (ALCL) at genome level. METHODS: ALK protein expression and molecular genetic abnormalities were detected by immunohistochemistry and fluorescence in situ hybridization, respectively, in 25 cases of ALCL. Any chromosomal gains/losses were detected by aCGH and correlated with ALK status. RESULTS: aCGH showed that chromosomal alterations in all 25 ALCL cases, and the frequency of chromosomal gains was higher than that of the losses. Chromosomal gains at 5p13.2, 3q21.1, 2q21.3, 3p25.1, 14q32.33, and 17q21.2 regions were detected in more than 50% of the ALCL cases; gains at 4q27, 6p22.1, 20p11.21, 2q22.3, 4q35.1, 1p36.22, 8p23.1, 8p12, 11q14.1, 12q13.13, and 19p13.3 regions were detected in 30%-50% of the ALCL cases; chromosomal losses at 3q26.1 and 3q26.31 regions were detected in 36.0% (9/25) and 24.0% (6/25) of the ALCL cases, respectively. Chromosomal gains at 2q21.3, 6p22.1 and 3p25.1 regions showed significant differences between ALK (+) and ALK (-) ALCL groups (P < 0.05). CONCLUSIONS: aCGH demonstrates complex molecular genetic variations in all ALCL cases. Gains at 2q21.3, 6p22.1 and 3p25.1 regions are significantly different between ALK (+) and ALK (-) ALCL groups, suggesting that the pathogenesis of ALK (+) and ALK (-) ALCL may involve different signaling pathway.


Assuntos
Aberrações Cromossômicas , Hibridização Genômica Comparativa/métodos , Linfoma Anaplásico de Células Grandes/enzimologia , Linfoma Anaplásico de Células Grandes/genética , Receptores Proteína Tirosina Quinases/metabolismo , Adolescente , Quinase do Linfoma Anaplásico , Feminino , Perfilação da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Inclusão em Parafina , Receptores Proteína Tirosina Quinases/genética
10.
Zhonghua Bing Li Xue Za Zhi ; 42(5): 299-304, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-24004585

RESUMO

OBJECTIVE: To investigate the molecular genetic abnormalities of N-myc and C-myc, and their clinical pathological implications in pediatric neuroblastic tumors (NTs). METHODS: Abnormalities of N-myc were detected by interphase fluorescence in situ hybridization (FISH) technique in 246 cases of NTs, including neuroblastoma (NB,188 cases), ganglioneuroblastoma (GNB, 52 cases), ganglioneuroma (GN, 6 cases), and their association with the histological typing of the tumors and prognosis was analyzed. Abnormalities of C-myc were detected by FISH in 133 cases of NTs. RESULTS: Of the 246 cases of NTs, N-myc amplification was only found in 27 cases (11.0%, 27/246) of NB, but not in any cases of GNB or GN (P < 0.05). 89.0% (219/246) N-myc non-amplification were found in NTs, and it included N-myc gain in 175 cases (71.1%, 175/246) and normal N-myc in 44 cases (17.9%, 44/246). Univariate analysis indicated significantly (P = 0.012) poorer outcome in patients with N-myc amplification than N-myc non-amplification. However no significant difference was observed between N-myc gain cases and normal N-myc cases (P = 0.057). C-myc gain was found in 74 of 133 cases (55.6%) of NTs; no C-myc amplification or translocation was detected. Forty percent (6/15) of cases with N-myc amplification and 57.6% (68/118) of cases with N-myc non-amplification were accompanied by C-myc gain. The difference between N-myc amplification and non-amplification with C-myc gain was not significant (P > 0.05). Univariate analysis indicated that the outcome difference was not statistically significant between C-myc gain cases and normal C-myc cases (P = 0.357). CONCLUSIONS: The incidence of N-myc amplification only found in NB is low in pediatric NTs in China. Patients with N-myc amplification predict poorer outcome. No amplification or translocation of C-myc is detected in NTs, whereas C-myc gain is relatively common in NTs. There is no obvious association between N-myc amplification and C-myc gain.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Amplificação de Genes , Genes myc , Neuroblastoma/patologia , Neoplasias das Glândulas Suprarrenais/genética , Criança , Pré-Escolar , Feminino , Seguimentos , Ganglioneuroblastoma/genética , Ganglioneuroblastoma/patologia , Ganglioneuroma/genética , Ganglioneuroma/patologia , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/patologia , Neuroblastoma/genética , Taxa de Sobrevida
11.
Diagn Cytopathol ; 41(6): 515-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22715132

RESUMO

The aim of this study was to determine the translocation and copy number change of the C-MYC gene in patients with laryngeal dysplasia and laryngeal squamous cell carcinoma (LSCC), and to evaluate the prevalence of such expression in relation to the normal-dysplasia-carcinoma sequence. Fluorescent in situ hybridization (FISH) was applied on formalin-fixed paraffin-embedded blocks of 93 laryngeal lesion specimens (14 normal epithelium, 15 mild dysplasia, 18 moderate dysplasia, 16 severe dysplasia, 9 carcinoma in situ, and 21 invasive carcinoma). C-MYC translocation was not observed in all laryngeal tissue. The high frequency for C-MYC copy-number increased (100%) in invasive carcinoma: 57.14% amplifications and 42.86% gains, and the positive rate of C-MYC amplification and copy-number change increased with the increasing severity of laryngeal lesions (P < 0.0001). The results suggest that C-MYC may be activated by gain/amplification in LSCC and precancerous lesions. Thus, C-MYC may play an important role in promoting LSCC progression, and early FISH detection of C-MYC may be exploited to set a screening test for laryngeal dysplasia.


Assuntos
Carcinoma de Células Escamosas/genética , Dosagem de Genes , Genes myc , Neoplasias Laríngeas/genética , Lesões Pré-Cancerosas/genética , Translocação Genética , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Epitélio/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Neoplasias Laríngeas/diagnóstico , Masculino , Pessoa de Meia-Idade
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(6): 1447-51, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23257451

RESUMO

This study was purposed to analyze the relation of N-myc gene copy number with clinical staging, pathological types and tumor biological factors in children with neuroblastoma (NB), and to investigate the influence of chemotherapy on N-myc gene expression and explore the relationship of N-myc gene copies with prognosis of NB children. The newly diagnosed children with NB from 1 March 2007 to 31 January 2011 were enrolled in this study. The treatment was carried out by BCH-NB-2007 based on Hongkong NB-07 protocol, and the patients were follow up to 31 January 2012. The N-myc gene in NB children was detected by FISH. According to number of N-myc gene copies, the NB children were divided into 3 groups. A group (N-myc gene negative) had less than 2 copies, B group (N-myc gene gains) had 3 to 9 copies, and C group (N-myc amplification) had more than 10 copies. The results showed that the N-myc gene expression in 58 cases of NB was observed. There were 36 males and 22 females. NB children aged from 6.5 to 138 months (median age 47.5 months), all patients were followed up for 11 - 57 months with an average of 31.5 months. INSS stages I-IV were 1, 5, 8 and 44 cases, respectively. Twenty-five cases had primary post mediastinal tumor, thirty-three cases had retroperitoneal and pelvic tumor, three of which also companied with post mediastinal tumor. Thirty-five cases had bone metastasis (60.3%), thirty-two cases had bone marrow metastasis (55%). Of the 54 patients with fully known biologic features, seventeen cases had ganglioneuroblastoma, thirty-seven cases had neuroblastoma (15 displayed differentiated, 7 poorly differentiated or undifferentiated, 15 with pathological changes after chemotherapy), four cases had bone marrow metastasis only detected by bone marrow biopsy. Eleven cases had N-myc gene negative, forty-three had N-myc gains, four had N-myc amplification. The average copy number of N-myc gene copies in 58 cases was 5.96 ± 7.81 in which 28 children were non chemotherapy cases, their average copy number was 4.00 ± 1.88, thirty cases out of 58 cases received preoperation chemotherapy (chemotherapy group), and their average copy number was 7.80 ± 10.46, the difference is significant (P = 0.064). The clinic stage, the location of primary tumor, pathological classification, urine VMA and serum neurogenic specific enolase had no effects on the N-myc gene expression, but the serum LDH level had influence (P < 0.01). Single factor Kaplan-Meier analysis showed that the number of N-myc gene copies in NB patients were closely related with the poor prognosis. The more copies of N-myc gene, the more poor prognosis, the difference is statistically significant (P < 0.05). It is concluded that the number of N-myc gene copies correlates with the rapid growth of NB and its poor prognosis, detecting the N-myc amplification can help to estimate the prognosis and decide the program of treatment. Serum LDH, which correlated with the rapid growth of NB, had effect on the N-myc gene expression and is closely related with the poor prognosis of NB.


Assuntos
Genes myc , Neuroblastoma/genética , Neuroblastoma/patologia , Criança , Pré-Escolar , Feminino , Amplificação de Genes , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Neuroblastoma/diagnóstico , Prognóstico
13.
Zhonghua Bing Li Xue Za Zhi ; 40(4): 227-34, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21615995

RESUMO

OBJECTIVE: To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD). METHODS: Twenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected. RESULTS: There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene. CONCLUSIONS: ASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Células Matadoras Naturais/patologia , Transtornos Linfoproliferativos/patologia , Linfócitos T/patologia , Adulto , Idoso , Complexo CD3/metabolismo , Feminino , Seguimentos , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Granzimas/metabolismo , Herpesvirus Humano 4/isolamento & purificação , Humanos , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/metabolismo , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a Poli(A)/metabolismo , RNA Viral/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Antígeno-1 Intracelular de Células T , Adulto Jovem
15.
Zhonghua Bing Li Xue Za Zhi ; 40(3): 169-72, 2011 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21575387

RESUMO

OBJECTIVE: To study clinicopathologic and genetic features of anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL). METHODS: Light microscopy, EliVision immunohistocheimical method and fluorescence in-situ hybridization were used to evaluate three ALK + LBCL cases recently diagnosed accompanied with a literature review. RESULTS: All three cases were male adult patients (mean age = 36.3 years) with nodal involvement by lymphoma. Histologic evaluation revealed a diffuse effacement of the nodal architecture by the infiltration of tumor cells. Sinusoidal infiltration was seen. The neoplastic cells were large and exhibited the immunoblastic/plasmablastic morphology. By immunohistochemistry, all the cases showed a cytoplasmic granular staining of ALK. They were positive for CD45, CD138, and epithelial membrane antigen (EMA), but were negative for CD3, CD20, CD79a and CD30. Fluorescence in situ hybridization (FISH) demonstrated the presence of ALK gene translocation in all of the cases. CONCLUSIONS: ALK + LBCL represents a distinct variant of diffuse large B-cell lymphoma, usually involving lymph node of middle-aged men. The tumor has a immunoblastic/plasmablastic morphology along with a distinct immunophenotypic profile and ALK gene rearrangement.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Translocação Genética , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Quinase do Linfoma Anaplásico , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígenos Comuns de Leucócito/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Mucina-1/metabolismo , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia
16.
Zhonghua Bing Li Xue Za Zhi ; 39(4): 235-9, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20654121

RESUMO

OBJECTIVE: To study the clinicopathologic features of 66 cases of primary systemic anaplastic large cell lymphoma (ALCL), with emphasis on the differences between ALK-positive and ALK-negative cases. METHODS: The clinical data of 66 cases of ALCL was analyzed. The histologic features were reviewed. Immunohistochemical study for CD30, ALK protein, epithelial membrane antigen, CD2, CD3, granzyme B and TIA-1 was carried out. In-situ hybridization for small mRNA of Epstein-Barr virus (EBER) was also performed. The chromosomal abnormalities were studied by fluorescence in-situ hybridization (FISH). The differences between ALK-positive and ALK-negative cases were statistically analyzed. RESULTS: There were 48 cases of ALK-positive ALCL and 18 cases of ALK-negative ALCL. The patients with ALK-positive ALCL were younger than those with ALK-negative ALCL (P < 0.05), with the median age being 18 years and 36 years, respectively. Fever, especially hyperpyrexia, was more commonly observed in ALK-positive ALCL patients than in ALK-negative ALCL patients (33 cases versus 4 cases, P < 0.05). The overall survival rate and median duration of survival in patients with ALK-positive ALCL were higher and longer than those in patients with ALK-negative ALCL (80% versus 71%; 21 months versus 12.5 months, P > 0.05). There were however no significant differences in histology between ALK-positive ALCL and ALK-negative ALCL. Histologically, most cases showed diffuse growth pattern. Nodular pattern was demonstrated in a minority of cases. "Hallmark" cells were seen in most of the ALCL cases. Focal necrosis and myxomatous stroma were identified in a few cases. Most ALK-positive cases belonged to the common variant (35 cases). A small number represented lymphohistiocytic variant (8 cases). Small cell variant and sarcomatoid subtype were found only in few cases (3 cases and 2 cases, respectively).On the other hand, common variant (17 cases) constituted the majority of ALK-negative ALCL. Lymphohistiocytic variant was seen in only 1 case. Immunohistochemical study showed that ALK-positive ALCL always expressed CD30 and epithelial membrane antigen. ALK-positive ALCL more often expressed epithelial membrane antigen (100% versus 72%; P < 0.05) but less so for T-cell markers (including CD2, CD3, CD43 and CD45RO). Cytotoxic molecules were more commonly expressed in ALK-positive ALCL (P > 0.05). EBER was negative in all cases studied. FISH showed that in ALK-positive ALCL, 1 case had normal ALK gene, 1 had deletion and multicopy and 2 had deletion. On the other hand, 1 case of ALK-negative ALCL had normal ALK gene. CONCLUSIONS: While there are no significant morphologic differences between ALK-positive ALCL and ALK-negative ALCL, the clinical features, immunophenotypes and genetic features of both groups vary. These differences are helpful in guiding the differential diagnosis.


Assuntos
Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Proteínas Tirosina Quinases/metabolismo , Adolescente , Adulto , Fatores Etários , Quinase do Linfoma Anaplásico , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Seguimentos , Deleção de Genes , Humanos , Antígeno Ki-1/metabolismo , Linfoma Anaplásico de Células Grandes/complicações , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/genética , Masculino , Hipertermia Maligna/etiologia , Pessoa de Meia-Idade , Mucina-1/metabolismo , Recidiva Local de Neoplasia , Proteínas Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases , Taxa de Sobrevida , Adulto Jovem
17.
Zhonghua Bing Li Xue Za Zhi ; 39(12): 819-24, 2010 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21215097

RESUMO

OBJECTIVE: To investigate the molecular genetic features and diagnostic aspects of sporadic Burkitt's lymphoma (BL) in children. METHODS: Tissue microarray was constructed to include 64 cases of pediatric BL and 6 cases of pediatric diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry and fluorescence in-situ hybridization for c-myc, bcl-2, bcl-6, IgH, myc/IgH and bcl-2/IgH gene were performed. Cases of pediatric Burkitt's lymphomas were subclassified into three groups based on their cellular orgins: the germinal center (GC) group, the late-germinal center (late-GC) group and the post-germinal center (post-GC) group. RESULTS: Among 64 Burkitt's lymphomas studied, expression of CD20, CD10, bcl-6, bcl-2 and MUM1 by immunohistochemistry were 100% (64 cases), 98.4% (63 cases), 96.9% (62 cases), 0 (0 cases) and 23.4% (15 cases), respectively. Various gene rearrangements were found involving the c-myc 93.1% (54/58 cases) and IgH 82.8% (48/58 cases). Detailed rearrangements are as follows: 46 cases (85.2%) myc/IgH gene translocation along with c-myc and IgH gene rearrangement; 4 cases (7.4%) c-myc gene rearrangement without IgH and myc/IgH abnormality; 4 cases (7.4%) without c-myc, IgH or myc/IgH gene rearrangement. No case showed bcl-2 gene abnormality (100%). Fifty nine cases showed normal bcl-6 gene status. One case had bcl-6 gene rearrangement and amplification with the pathologic and immunophenotypic characteristics of BL, leading to a revised pathological diagnosis of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (DLBCL/BL). Two cases showed c-myc gene rearrangement. Two cases showed bcl-6 gene amplification and 6 DLBCL cases had a normal status of bcl-2/IgH. CONCLUSIONS: A majority of pediatric sporadic BL arise from the germinal center B cells, most of which have c-myc gene rearrangement. It is useful to distinguish BL and DLBCL by multiple genes detection.


Assuntos
Antígenos CD20/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Cadeias Pesadas de Imunoglobulinas/genética , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Genes myc/genética , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Neprilisina/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Translocação Genética
18.
Zhonghua Bing Li Xue Za Zhi ; 38(8): 513-8, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-20021960

RESUMO

OBJECTIVE: To study the role of pathogenic microorganisms commonly associated with chronic eye disease, including Chlamydia psittaci, Chlamydia trachomatis, Chlamydia pneumoniae, herpes simplex virus (HSV) type 1 and type 2, and adenovirus type 8 and type 19, in the development of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma in Chinese patients. METHODS: Sixty-eight archival cases of primary ocular adnexal lymphoproliferative lesions, including 38 cases of MALT lymphoma, 3 cases of non-MALT lymphoma and 27 cases of chronic inflammation, were enrolled into the study. DNA was extracted from the paraffin-embedded tissue samples. The presence of DNA of C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 were analyzed by multiplex touchdown enzyme time-release polymerase chain reaction (TETR-PCR). RESULTS: All of the specimens yielded PCR products of over 100 base pairs and were thus suitable for TETR-PCR screening of infectious agents. The prevalence of DNA of C. psittaci, C. trachomatis and adenovirus type 19 were 0 in MALT lymphoma, non-MALT lymphoma and chronic inflammation. There were 2 cases positive for C. pneumoniae DNA, amongst the 38 cases of MALT lymphoma studied (5.3%, 2/38). HSV type 1, HSV type 2 and adenovirus type 8 DNA was found in each of the 3 patients with chronic inflammation. CONCLUSION: The study indicates that C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 probably play little role in the pathogenesis of ocular adnexal MALT lymphoma in Chinese patients.


Assuntos
DNA Bacteriano/análise , DNA Viral/análise , Infecções Oculares , Neoplasias Oculares , Linfoma de Zona Marginal Tipo Células B , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/genética , Adenovírus Humanos/isolamento & purificação , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Infecções por Chlamydophila/microbiologia , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/isolamento & purificação , Chlamydophila psittaci/genética , Chlamydophila psittaci/isolamento & purificação , Infecções Oculares/microbiologia , Infecções Oculares/virologia , Neoplasias Oculares/microbiologia , Neoplasias Oculares/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/isolamento & purificação , Humanos , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/virologia , Psitacose/microbiologia
19.
Zhonghua Nei Ke Za Zhi ; 48(3): 181-5, 2009 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-19576081

RESUMO

OBJECTIVE: To investigate the genetic aberrations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. METHODS: Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t (11; 18) (q21; q21)/API2-MALT1, t (1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. RESULTS: These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t (11; 18) (q21; q21) API2-MALT1 13% (29/217), t (1; 14) (p22; q32) IGH-BCL10 in 1% (3/217), t (14; 18) (q32; q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t (11; 18) (q21; q21) API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47%, 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6%, 4/68). t (1; 14) (p22; q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t (14; 18) (q32; q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17%, 1/6) and stomach (4%, 3/84). CONCLUSIONS: It is demonstrated that the four translocations occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.


Assuntos
Linfoma de Zona Marginal Tipo Células B/genética , Translocação Genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Criança , Feminino , Humanos , Hibridização in Situ Fluorescente , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Zhonghua Bing Li Xue Za Zhi ; 38(11): 739-44, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20079012

RESUMO

OBJECTIVE: To evaluate the efficiency of the BIOMED-2 PCR assay and its implication in the diagnosis of mature B-cell non-Hodgkin's lymphomas. METHODS: Clinical, morphological and immunohistochemical features of 72 cases of non-Hodgkin's lymphomas were studied, including 25 reactive lymphoid hyperplasia, 37 diffuse large B cell lymphomas (DLBCL) and 35 extranodal marginal zone lymphomas of mucosa associated lymphoid tissues (MALT lymphoma and in addition, 25 cases of reactive lymphoid hyperplasia were used as the controls). DNA was exacted from the paraffin embedded formalin fixed tissue blocks and the quality of DNA was assessed using the BIOMED-2 specimen control reaction. Adequate samples were then analyzed by BIOMED-2 for immunoglobulin heavy and kappa light chain rearrangements. RESULTS: Adequate DNA was obtained in 83 of 97 samples, including 60 mature B cell lymphomas and 23 reactive lymphoid hyperplasia. Clonal B-cell gene rearrangements were detected in 57 of 60 (95%) lymphomas. In contrast, clonal Ig gene rearrangements were not detected in any of the 23 cases of reactive lymphoid hyperplasia. CONCLUSION: BIOMED-2 assay is highly sensitive and specific for the detection of clonal B cell gene rearrangement using routine paraffin embedded formalin fixed specimens.


Assuntos
Rearranjo Gênico do Linfócito B/genética , Genes de Imunoglobulinas , Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Antígenos CD20/metabolismo , Antígenos CD79/metabolismo , DNA de Neoplasias/genética , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Rearranjo Gênico de Cadeia Leve de Linfócito B/genética , Humanos , Imunofenotipagem , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Inclusão em Parafina , Pseudolinfoma/genética , Pseudolinfoma/imunologia , Pseudolinfoma/patologia , Sensibilidade e Especificidade
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