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1.
Oncotarget ; 8(55): 94944-94950, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29212280

RESUMO

OBJECTIVES: It is not clear whether being overweight or obese influences postoperative complications in myasthenia gravis (MG) patients. We retrospectively investigated an association between body mass index (BMI) and postoperative complications in MG. MATERIALS AND METHODS: Fifty-nine MG patients who had undergone transsternal thymectomy were classified as low or high BMI based on the criteria for Asian-Pacific populations. An association between BMI and complications was analyzed. RESULTS: MG patients with high BMI had significantly higher rates of major adverse complications (P = 0.033), postoperative respiratory failure (P = 0.045), and longer postoperative hospitalization (P = 0.005). The optimal cutoff value of BMI for postoperative respiratory failure was 23.3 kg/m2, with a sensitivity of 75.0% and a specificity of 64.7% (P = 0.046). CONCLUSIONS: MG patients with a BMI indicating overweight or obesity have a higher risk of postoperative complications after thymectomy. Thus, close monitoring must be performed when surgery is necessary.

2.
Biomed Res Int ; 2017: 3856839, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28948165

RESUMO

OBJECTIVE: We aimed to investigate how the embryonic stem cell-related gene Oct3/4 changes during the injury-repair process of distal pulmonary epithelium induced by 5-fluorouracil (5-Fu). METHODS: We have developed the lung injury model induced by 5-Fu and observed the dynamic changes of Oct3/4 by indirect immunofluorescence, Western blot, and quantitative real-time PCR. Immunofluorescence double staining was used to compare the positions of Oct3/4(+) cells and other reported alveolar epithelial stem cells. RESULTS: Oct3/4(+) cells were not found in normal rat lung epithelial cells. However, after treatment with 5-Fu, Oct3/4(+) cells appeared at 12 h, reached the peak at 24 h, then decreased at 48 h, and eventually disappeared at 72 h. Oct3/4 was localized in the nucleus. We found that the sites of Clara cell secretory protein and surfactant protein-C dual positive cells were apparently different from Oct3/4(+) cells. CONCLUSIONS: Our results revealed that, in rat alveolar epithelium, expression of Oct3/4 could be induced after treatment with 5-Fu, then decreased gradually, and was silenced following the alveolar epithelial differentiation. We hold that Oct3/4(+) cells are lung stem cells, which can provide new evidence for identification and isolation of lung epithelial stem cells.


Assuntos
Células Epiteliais Alveolares/metabolismo , Fluoruracila/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Lesão Pulmonar/metabolismo , Fator 3 de Transcrição de Octâmero/biossíntese , Mucosa Respiratória/metabolismo , Células-Tronco/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Feminino , Fluoruracila/farmacologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Mucosa Respiratória/patologia , Células-Tronco/patologia
3.
Oncotarget ; 7(17): 23730-9, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27009861

RESUMO

Accurate markers and molecular mechanisms of stem cell dormancy and activation are poorly understood. In this study, the anti-cancer drug, 5-fluorouracil, was used to selectively kill proliferating cells of human bronchial epithelial (HBE) cell line. This method can enrich and purify stem cell population. The dormant versus active status of stem cells was determined by phosphorylation of RNAp II Ser2. The surviving stem cells were cultured to form stem cell spheres expressing stem cell markers and transplanted into nude mice to form a teratoma. The results demonstrated the properties of stem cells and potential for multi-directional differentiation. Bisulfite sequencing polymerase chain reaction showed that demethylation of the Sox2 promoter by 5-FU resulted in Sox2 expression in the dormant stem cells. This study shows that the dormancy and activation of HBE stem cells is closely related to epigenetic modification.


Assuntos
Brônquios/patologia , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição SOXB1/genética , Células-Tronco/patologia , Teratoma/patologia , Neoplasias da Traqueia/patologia , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Diferenciação Celular , Proliferação de Células , Metilação de DNA , Epigênese Genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Regiões Promotoras Genéticas , RNA Polimerase II/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Teratoma/tratamento farmacológico , Teratoma/metabolismo , Neoplasias da Traqueia/tratamento farmacológico , Neoplasias da Traqueia/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Cell Biochem Biophys ; 70(3): 1691-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25149649

RESUMO

Although the research on the localization of trachea stem cells has made a rapid progress, the mechanism of proliferation and differentiation of trachea stem cells remains unclear. The objective of this study is to observe and analyze the recovery process of mice tracheal epithelium injured by 5-FU, and to investigate the mechanism involved in the regulation of tracheal stem cells proliferation and differentiation through morphological, immunofluorescence, and microarray analysis. After treatment with 5-FU, the mature cells were dead and desquamated. Only a few G0 phase cells remained on the basement membrane. When supplied with normal culture media, the cells eventually became flat, cubic, and restored as pseudostratified epithelium. These G0 phase cells were ABCG2 positive. It suggested that these cells could differentiate into cilia cells or Clara cells, and had the multi-differentiation ability of stem cells. We examinated the expression profile of genes involved in the stem cell differentiation in normal tracheal epithelial cells and the regenerated epithelial cells at 24 and 48 h after injured by 5-FU using gene microarray. After 24 h treatment, 8 genes were up-regulated and 31 genes were down-regulated. After 48 h treatment, 5 genes were up-regulated and 42 genes were down-regulated. The differential gene expressions in gene microarray analysis focused on cell cycle regulation, intercellular junction, fibroblast growth factors, bone morphogenetic protein, Notch and Wnt-signaling pathways, which suggested that the differential gene expressions might be closely associated with the proliferation and differentiation of tracheal stem cells.


Assuntos
Células Epiteliais/efeitos dos fármacos , Fluoruracila/toxicidade , Traqueia/citologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Imunofluorescência , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Traqueia/patologia , Regulação para Cima/efeitos dos fármacos
5.
J Transl Med ; 11: 232, 2013 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-24070213

RESUMO

BACKGROUND: Oct4 is a major transcription factor related to stem cell self-renewal and differentiation. To fulfill its functions, it must be able to enter the nucleus and remain there to affect transcription. KPNA2, a member of the karyopherin family, plays a central role in nucleocytoplasmic transport. The objective of the current study was to examine the association between Oct4 and KPNA2 expression levels with regard to both the clinicopathological characteristics and prognoses of patients with non-small-cell lung cancer (NSCLC). METHODS: Immunohistochemistry was used to detect the expression profile of Oct4 and KPNA2 in NSCLC tissues and adjacent noncancerous lung tissues. Real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression profiles of Oct4 and KPNA2 in lung cancer cell lines. Small interfering RNAs were used to deplete Oct4 and KPNA2 expressions. Double immunofluorescence was used to detect Oct4 expression in KPNA2 knockdown cells. Co-immunoprecipitation was used to detect the interaction of Oct4 and KPNA2. RESULTS: Oct4 was overexpressed in 29 of 102 (28.4%) human lung cancer samples and correlated with differentiation (P = 0.002) and TNM stage (P = 0.003). KPNA2 was overexpressed in 56 of 102 (54.9%) human lung cancer samples and correlated with histology (P = 0.001) and differentiation (P = 0.045). Importantly, Oct4 and KPNA2 expression levels correlated significantly (P < 0.01). Expression of Oct4 and KPNA2 was associated with short overall survival. In addition, depleting Oct4 and KPNA2 expression using small interfering RNAs inhibited proliferation in lung cancer cell lines. Real-time polymerase chain reaction and western blotting analysis indicated that reduction of KPNA2 expression significantly reduced mRNA and nucleoprotein levels of Oct4. Double immunofluorescence analysis revealed that nuclear Oct4 signals were reduced significantly in KPNA2 knockdown cells. Co-immunoprecipitation experiments revealed that KPNA2 interacts with Oct4 in lung cancer cell lines. CONCLUSION: Oct4 and KPNA2 play an important role in NSCLC progression. Oct4 nuclear localization may be mediated by its interaction with KPNA2.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Fator 3 de Transcrição de Octâmero/genética , alfa Carioferinas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fator 3 de Transcrição de Octâmero/metabolismo , Ligação Proteica , alfa Carioferinas/metabolismo
6.
Tumour Biol ; 34(3): 1503-10, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23359275

RESUMO

Most adult stem cells are in the G0 or quiescent phase of the cell cycle and account for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. This study sought to enrich cancer stem cells and explore cancer stem-like cell clones using 5-fluorouracil (5-FU) in the lung adenocarcinoma cell line, SPC. Proliferation inhibition was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, according to which half maximal inhibitory concentration values were calculated. Expression levels of stem cell markers after treatment with 5-FU were examined using immunofluorescence and Western blotting. Additionally, side population (SP) cells were sorted using FACS. Properties of SP cells were evaluated by using Transwell, colony-forming assays, and tumor formation experiments. 5-FU greatly inhibits proliferation, especially of cells in S phase. SP cells possess greater invasive potential, higher clone-forming potential, and greater tumor-forming ability than non-SP cells. Treatment with 5-FU enriches the SP cells with stem cell properties in human lung adenocarcinoma cell lines.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Movimento Celular/efeitos dos fármacos , Fluoruracila/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células da Side Population/efeitos dos fármacos , Células da Side Population/metabolismo , Células da Side Population/patologia , Células Tumorais Cultivadas
7.
Mol Med Rep ; 1(5): 651-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-21479464

RESUMO

The present study examines clinicopathologic findings and their association with the Epstein-Barr virus (EBV) in Waldeyer's ring lymphomas (WRLs) from Indonesia (91 cases), P.R. China (31 cases), Korea (101 cases) and Japan (61 cases). Waldeyer's ring (WR) was categorized into upper and lower parts comprising the pharyngeal and tubal tonsils (upper WR) or palatine and lingual tonsils (lower WR), respectively. Diffuse large B-cell lymphoma (DLBCL) pre-dominated in the lower WR in all countries at a frequency of 78.9-100%. Natural killer/T-cell lymphoma (NKTCL) was predominant in the upper WR in China, Korea and Japan at a frequency of 50-62.5%, while in Indonesia it occcurred at a frequency of less than 10%. On the whole, patients with NKTCL were significantly younger (median 43 years) than those with DLBCL (57 years). Patients with DLBCL in the lower WR were significantly younger in Indonesia (median 50 years) than in China (63 years) or Japan (69 years). The percentage of EBV-positive cases was much higher in NKTCL (78.6-100%) than in DLBCL (2.2-6%). This study evaluates the differences between East and Southeast Asian countries in terms of histologic type and age distribution in WRLs categorized by the location of the lesions in WR.

8.
Zhonghua Bing Li Xue Za Zhi ; 36(2): 94-7, 2007 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-17493382

RESUMO

OBJECTIVE: To study the clinical features, immunophenotypes and the significance of Epstein-Barr virus infection in primary nasal and pharyngeal non-Hodgkin's lymphomas in Shenyang. METHODS: One hundred and fifty eight cases of primary nasal and pharyngeal non-Hodgkin's lymphomas were included in this study. The samples were stained with haematoxylin and eosin for histological examination. Immunohistochemistry studies were performed using monoclonal antibodies, including CD3 for T-lymphocytes, CD20 for B-lymphocytes, and CD56 and CD57 for NK cells. All cases were reclassified according to the new WHO classification of lymphomas (2001). In situ hybridization detection of EBV-encoded small nuclear RNA (EBER-1) was performed in 99 cases. RESULTS: Overall, 101 (63.9%) of the 158 NHL were extranodal NK/T cell lymphomas (nasal type), 23 (14.6%) were nonspecific peripheral T cell lymphomas and the remaining 34 cases (21.5%) were B cell lymphomas. The primary sites of involvement were the nasal cavity (53.2%, 84/158), the tonsil (24.7%, 39/158) and the pharynx (22.1%, 35/158). Among 99 cases studied by EBER-1 in situ hybridization, a positive detection was seen in 70/71 cases (98.6%) of extranodal NK/T cell lymphoma (nasal type), 8/12 cases (66.7%) of T cell lymphoma, and 7/16 cases (43.8%) of B cell lymphoma. CONCLUSIONS: Among primary nasal and pharyngeal NK lymphomas, extranodal NK/T cell lymphoma (nasal type) is the most common type and is strongly associated with EBV infection. The pathological diagnosis of nasal and pharyngeal lymphomas should take considerations of the anatomic sites and immunophenotypical features.


Assuntos
Herpesvirus Humano 4/isolamento & purificação , Linfoma não Hodgkin , Cavidade Nasal , Neoplasias Nasais , Neoplasias Faríngeas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo CD3/metabolismo , Antígeno CD56/metabolismo , Criança , Feminino , Humanos , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma de Células B/virologia , Linfoma Extranodal de Células T-NK/metabolismo , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/virologia , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/virologia , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/metabolismo , Neoplasias Nasais/patologia , Neoplasias Nasais/virologia , Neoplasias Faríngeas/metabolismo , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/virologia , RNA Viral/metabolismo , Neoplasias Tonsilares/metabolismo , Neoplasias Tonsilares/patologia , Neoplasias Tonsilares/virologia , Adulto Jovem
9.
Int J Cancer ; 120(2): 406-10, 2007 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17066445

RESUMO

Cases of nasal NK/T-cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life-style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000-2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74-9.87) for farmers, 2.81 (CI, 1.49-5.29) for producers of crops, 4.01 (CI, 1.99-8.09) for pesticide users, 11.65 (CI, 1.17-115.82) for residents near garbage burning plants, 2.95 (CI, 1.25-6.95) for former drinkers, and 0.49 (CI, 0.23-1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28-8.54), 1.18 (95% CI, 0.11-12.13) and 2.20 (95% CI, 0.88-5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life-style and environmental factors might be risk factors for NKTCL.


Assuntos
Poluentes Ambientais/toxicidade , Células Matadoras Naturais , Estilo de Vida , Linfoma de Células T/epidemiologia , Neoplasias Nasais/epidemiologia , Praguicidas/toxicidade , Adulto , Idoso , Estudos de Casos e Controles , Ásia Oriental/epidemiologia , Feminino , Humanos , Incidência , Linfoma de Células T/prevenção & controle , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/prevenção & controle
10.
Zhonghua Bing Li Xue Za Zhi ; 33(2): 143-5, 2004 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15132852

RESUMO

OBJECTIVE: Localization of tracheal stem cells in rat trachea. METHODS: Extracorporeal tracheal injury (Wistar rats) was induced by 5-FU. The process of regeneration was observed and analyzed by light microscopy, electron microscopy, and immunohistochemistry. RESULTS: Twelve hours after treatment with 5-FU, the tracheal epithelium shed and cells with naked nuclei were seen located sparsely on the basement membrane. Six hours after removal of 5-FU, the tracheal rings were covered with flattened epithelium. These cells were poorly differentiated under electron microscopy. Immunohistochemistry showed few proliferating cell nuclear antigen (PCNA)-negative cells sparsely scattered among PCNA-positive cells on the basement membrane. Nine hours later, electron microscopy found that these cells differentiated into mucous cells and ciliated cells. Forty-eight hours later, the tracheal rings were entirely covered by pseudostratified ciliated columnar epithelium. CONCLUSIONS: A small number of G(0) cells with naked nuclei are located sparsely on the basement membrane of the trachea. Tracheal epithelium regenerates by proliferation and differentiation of these cells. It is likely that some of these G(0) cells on the tracheal basement membrane represent tracheal stem cells.


Assuntos
Regeneração , Traqueia/lesões , Traqueia/fisiologia , Cicatrização/fisiologia , Animais , Diferenciação Celular , Proliferação de Células , Epitélio/lesões , Epitélio/ultraestrutura , Feminino , Fluoruracila , Masculino , Microscopia Eletrônica , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , Células-Tronco , Traqueia/patologia
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