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1.
Zhonghua Zhong Liu Za Zhi ; 46(4): 354-364, 2024 Apr 23.
Artículo en Chino | MEDLINE | ID: mdl-38644271

RESUMEN

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (<60, 60-<70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.


Asunto(s)
Detección Precoz del Cáncer , Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/sangre , Antígeno Prostático Específico/sangre , Anciano , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Factores de Edad , Curva ROC , China , Sensibilidad y Especificidad , Tamizaje Masivo/métodos , Área Bajo la Curva
2.
Eur Rev Med Pharmacol Sci ; 25(19): 6123-6130, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34661272

RESUMEN

OBJECTIVE:   The aim of this study is to investigate the clinical value of low-dose spiral CT (LDCT), plasma miR-200b, and miR-200c combined screening for lung cancer screening in the physical examination population. PATIENTS AND METHODS: From January 2016 to December 2018, the Physical Examination Center of our hospital underwent low-dose spiral CT lung cancer screening for 10,823 people aged ≥40 years. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the relative expressions of miR-200b and miR-200c in plasma, analyze the imaging characteristics of suspicious nodules in the lung and the relative expressions of miR-200b and miR-200c in plasma. RESULTS: A total of 2,919 pulmonary nodules were detected in the 10823 physical examination population, with a total detection rate of 26.97%, including 1523 males and 1396 females. 1081 positive nodules were detected with a detection rate of 9.99%. According to the Lung-RADS classification, the number of type 2 nodules was the highest, with a detection rate of 22.13%. Meanwhile, the rate of type 3 nodules was 3.15%, and the rate of type 4 nodules was 1.69%. The sensitivity, accuracy, and negative predictive value of LDCT, miR-200b, and miR-200c in the diagnosis of lung cancer were significantly improved compared with the individual tests, which were 94.74%, 90.16%, and 95.88%, respectively. CONCLUSIONS: Low-dose spiral CT combined with plasma miR-200b and miR-200c for lung cancer screening in the physical examination population can help to detect lung cancer patients with early symptoms that are not significant, and achieve early diagnosis and early treatment.


Asunto(s)
Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares/diagnóstico por imagen , MicroARNs/genética , Tomografía Computarizada Espiral/métodos , Adulto , Anciano , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Tamizaje Masivo/métodos , MicroARNs/sangre , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad
3.
Eur Rev Med Pharmacol Sci ; 25(6): 2493-2502, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33829435

RESUMEN

OBJECTIVE: To evaluate metabolic parameters of primary lesions examined by 18F-FDG PET/CT (18Fluorodeoxyglucose Positron Emission Tomography /Computed Tomography), including maximum standard uptake value (SUVmax), metabolic volume (MTV), and total lesion glycolysis (TLG). PATIENTS AND METHODS: 79 patients with endometrial cancer were selected as the subjects. They were diagnosed by histopathology in our hospital for the first time from January 2016 to December 2018. All the patients were examined by 18F-FDG PET/CT. Retrospective statistical analysis was carried out to evaluate different expression of metabolic parameters examined by 18F-FDG PET/CT of different clinicopathologic factors in endometrial cancer. Spearman correlation analysis was also used. RESULTS: SUVmax, TLG and MTV were correlated with FIGO staging, tissue grading, depth of myometrial invasion, and lymph node metastasis. SUVmax, TLG and MTV in lymph node metastasis group had high clinical staging, low differentiation and myometrial invasion depth >1/2, which were significantly higher than those in no lymph node metastasis group (low clinical staging, high differentiation and myometrial invasion depth ≤1/2). TLG had the greatest difference(p<0.001). TLG and MTV were correlated with histopathological classification (p<0.05). The expression levels of SUVmax, MTV and TLG of primary lesions were negatively correlated with the positive expression of ER and PR in tumor tissues (p<0.05), and significantly positively correlated with positive expression of HER -2 and Ki-67 (p<0.01). The expression of ER, PR, HER-2 and KI-67 in tumor tissues was correlated with tissue grading, clinical staging, depth of muscular layer infiltration, cervical tissue involvement and lymph node metastasis (p<0.05). CONCLUSIONS: Metabolic parameters of primary lesions examined by 18F-FDG PET/CT has a good correlation with its clinicopathological features. They can provide reference for the preoperative formulation of treatment plan for endometrial cancer, so as to reduce the risk of surgery and improve the prognosis of patients.


Asunto(s)
Neoplasias Endometriales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Inmunohistoquímica , Persona de Mediana Edad
5.
Zhonghua Nei Ke Za Zhi ; 58(1): 49-55, 2019 Jan 01.
Artículo en Chino | MEDLINE | ID: mdl-30605951

RESUMEN

Objective: To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods: In this prospective study, adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumor tissues were detected by ADx-amplification refractory mutation system (ADx-ARMS). EGFR mutations of plasma free tumor DNA were detected by ADx-ARMS and ADx-super amplification refractory mutation system (ADx-SuperARMS) at the same time. Patients with EGFR-mutant in tumor tissues and receiving EGFR-TKIs were finally enrolled. Plasma mutation-positive patients with both methods were high abundance group.Patients with positive mutations by ADx-SuperARMS but negative by ADx-ARMS were medium abundance group. Mutation-negative patients with both methods were recognized as low abundance group. The correlation between EGFR mutation abundance and clinical response to EGFR-TKIs were analyzed. Results: Among 71 patients enrolled, 42 harbored EGFR mutations in plasma were detected by ADx-ARMS, while 53 were found by ADx-SuperARMS.There were 42 patients in high abundance group, 11 in medium group while the other 18 in low group. The objective response rates (ORRs) were 69.0%, 7/11 and 10/18 in high, medium and low groups, respectively. The difference was significant between high and low abundances groups (P=0.006). Median progression-free survival (PFS) in high, medium and low groups were 11.0, 8.5 and 9.0 monthes, respectively (P<0.001). In patients with tumor 19-Del, the ORRs were 70.4%, 5/7 and 6/11 in high, medium and low abundance groups, respectively. The median PFS of high abundance group was significantly longer than the other two groups (12.0 monthes vs 9.0, 9.0 monthes). As to subjects with L858R mutation, the ORRs were 10/15, 2/4 and 3/6, respectively, with median PFS 9.6, 5.5 and 9.5 monthes. Conclusions: The relative abundance of EGFR mutations in plasma predicts clinical response to EGFR-TKIs in patients with advanced lung adenocarcinoma. The higher the mutation abundance is, the better the efficacy of EGFR-TKIs is.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Adenocarcinoma del Pulmón/enzimología , Adenocarcinoma del Pulmón/patología , Adulto , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Humanos , Neoplasias Pulmonares/enzimología , Mutación , Supervivencia sin Progresión , Estudios Prospectivos
6.
Zhonghua Nei Ke Za Zhi ; 57(12): 907-911, 2018 Dec 01.
Artículo en Chino | MEDLINE | ID: mdl-30486559

RESUMEN

Objective: To compare the diagnostic value of the old "ABC" method [serum pepsinogen(PG) combined with Helicobacter pylori (Hp) IgG antibody] and the new "ABC" method [serum pepsinogen plus gastrin-17(G-17)] in screening gastric cancer and its precancerous condition. Methods: Serum PG, G-17 and Hp-IgG were quantified by enzyme-linked immunosorbent assay (ELISA) in 278 subjects. Subjects were grouped according to the criteria of two methods. The gastroscopy and pathological biopsy were gold standard. Results: The positive rate of old "ABC" method was 74.46% (207/278), which was 54.68% of new "ABC" method (151/278). For the diagnosis of gastric cancer, the sensitivity and specificity of the old "ABC" method were 90.74% and 29.46% respectively, with diagnostic coincidence rate 41.37%. The sensitivity and specificity of the new "ABC" method were 92.59% and 54.46% respectively, with diagnostic coincidence rate 61.87%. As to the diagnosis of pre-cancerous state, the sensitivity and specificity of the old "ABC" method were 75.81% and 36.00%, with diagnostic coincidence rate 58.03%. The sensitivity and specificity of the new "ABC" method were 62.10% and 75.00%, with diagnostic coincidence rate 67.86%. Conclusions: Compared with the old "ABC" method, the new "ABC" method has higher sensitivity, specificity and diagnostic coincidence rate for the diagnosis of gastric cancer, yet higher specificity and lower sensitivity for the diagnosis of precancerous conditions.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Detección Precoz del Cáncer/métodos , Gastrinas/sangre , Gastroscopía , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Pepsinógeno A/sangre , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/microbiología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Lesiones Precancerosas/sangre , Sensibilidad y Especificidad , Neoplasias Gástricas/sangre
7.
Artículo en Chino | MEDLINE | ID: mdl-29921073

RESUMEN

Objective:To evaluate the surgical methods and outcomes of laryngeal stenosis after laryngeal cancer surgery. Method:Nineteen patients with laryngeal stenosis caused by partial laryngectomy were retrospectively analyzed.Two cases were treated by endoscopic laser resection. Seventeen were treated by open surgery. Among them 15 used the sternohyoid myocutaneous flap and 1 thyroid alar cartilage and 1 hyoid bone as grafts. Result:Sixteen patients were decannulated and the overall decannulation rate was 84%. A silicone T tube was remained in place from 3 to 18 months, mean 10 months. Follow-up was obtained from 11 months to 8 years. Conclusion:Vertical partial laryngectomy easily lead to laryngeal stenosis. The sternohyoid myocutaneous flap is the major approach for laryngeal stenosis. Endoscopic laser resection is effective for mild stenosis.


Asunto(s)
Neoplasias Laríngeas/cirugía , Laringectomía/efectos adversos , Laringoestenosis/cirugía , Humanos , Hueso Hioides , Laringoestenosis/etiología , Estudios Retrospectivos
8.
Eur Rev Med Pharmacol Sci ; 22(11): 3430-3438, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29917195

RESUMEN

OBJECTIVE: To explore the effects of microRNA-1266 (miR-1266) on metastasis and growth in papillary thyroid carcinoma cells and to provide therapeutic targets for papillary thyroid carcinoma. PATIENTS AND METHODS: By quantitative Real-time polymerase chain reaction (PCR), miR-1266 expression level in 38 pairs of papillary thyroid carcinoma tissues and three breast cancer-derived cell lines was examined. After transfection with miR-1266 mimics, the effects of miR-1266 over-expression on cell proliferation, invasion and migration were analyzed. Further, we employed several databases for the target gene prediction. Dual-luciferase activity assay was performed to verify whether FGFR2 was the direct target gene of miR-1266. Western blotting was conducted to detect protein levels. RESULTS: MiR-1266 was significantly downregulated in papillary thyroid carcinoma tissue samples and cell lines. Over-expression of miR-1266 in papillary thyroid carcinoma cells significantly attenuated the cell proliferation, invasion, and migration. Dual-luciferase report assay and Western blotting confirmed that FGFR2 was a target gene of miR-1266. Furthermore, up-regulation of FGFR2 partially reversed the suppressive effects of miR-1266 over-expression on cell growth and progression. CONCLUSIONS: miR-1266 could inhibit cell proliferation and progression of papillary thyroid carcinoma via targeting FGFR2. Our findings might provide a new target for the diagnosis and treatment of papillary thyroid carcinoma.


Asunto(s)
MicroARNs/fisiología , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/prevención & control , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/biosíntesis , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/metabolismo , Regulación hacia Arriba
9.
Eur Rev Med Pharmacol Sci ; 22(9): 2707-2714, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29771422

RESUMEN

OBJECTIVE: To identify the role of hsa-miR-196a-2 in thyroid cancer by bioinformatics analysis. MATERIALS AND METHODS: The expression profiles of thyroid cancer was download from TCGA. The dysregulated microRNAs were obtained by edger R package. Then, the prognostic data were analyzed by K-M plot. The difference between different groups was analyzed by the t-test. At last, the biological processes of has-miR-196a-2 were obtained with GSEA. RESULTS: In this study, we found that has-miR-196a-2 was upregulated in thyroid carcinoma by analyzing the TCGA database, which was inversely proportional to the prognosis of patients with thyroid carcinoma. Univariate and multivariate COX analysis showed that has-miR-196a-2 was an independent prognostic risk factor for thyroid carcinoma. Higher expressions of has-miR-196a-2 were found in patients with older age, advanced tumor stage, lymph node metastasis, and local infiltration through the t-test. We found that has-miR-196a-2 was enriched in adherent junction, focal adhesion, and actin cytoskeleton, which are closely related to the invasion and migration of the function pathway. Moreover, it is mainly enriched in tumor progression pathways, such as the PPAR pathway and WNT pathway. CONCLUSIONS: Hsa-miR-196a-2 is overexpressed in thyroid tumors and is an independent prognostic risk factor for thyroid carcinoma.


Asunto(s)
Carcinoma/metabolismo , MicroARNs/metabolismo , Neoplasias de la Tiroides/metabolismo , Carcinoma/genética , Carcinoma/secundario , Bases de Datos Factuales , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , MicroARNs/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Riesgo , Transducción de Señal , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Regulación hacia Arriba
10.
Zhonghua Yi Xue Za Zhi ; 97(27): 2087-2090, 2017 Jul 18.
Artículo en Chino | MEDLINE | ID: mdl-28763880

RESUMEN

Objective: To detect the serum resistin levels in patients with generalized myasthenia gravis (GMG) and evaluate the clinical values of resistin. Methods: We detected the serum resistin levels in 58 patients with GMG and 58 healthy controls (HC) from January 2013 to December 2015 in Tianjin medical university general hospital.Then we analyzed the correlation of the serum resistin levels with the clinical features. Results: The serum resistin levels in patients with GMG, (8.26±4.27) ng/ml, was significantly higher than in HC, (4.12±1.36) ng/ml, (P<0.001). There was no statistical difference of the serum resistin levels between female or male patients with GMG (P=0.589). The serum resistin levels in patients with GMG was positively correlated with the quantitative MG score for disease severity (QMG) (r=0.446, P<0.001), but not correlated with age (r=0.168, P=0.206). The patients with higher resistin levels took higher risk of combining with thymoma (P=0.002), 56.5%, and these patients had higher QMG, 11(5) (P=0.001); and the ratio and QMG in the patients with lower resistin levels were 17.1%, 7(5), respectively.The GMG patients with thymoma (TGMG+ ) had remarkably higher serum resistin levels, (10.7±5.3) ng/ml (P=0.010) and the QMG score, 11(5) (P<0.001) than the GMG patients without thymoma (TGMG-) with (7.0±3.1) ng/ml and 8(5). Conclusion: Resistin is probably associated with the severity of the disease of MG, and maybe a potential biomarker of MG combined with thymoma.


Asunto(s)
Miastenia Gravis , Femenino , Humanos , Masculino , Resistina
11.
Zhonghua Yi Xue Za Zhi ; 97(24): 1862-1866, 2017 Jun 27.
Artículo en Chino | MEDLINE | ID: mdl-28648009

RESUMEN

Objective: To evaluate the performance of T cell enzyme-linked immuno-spot assay (T-SPOT) on peripheral blood in combination with adenosine deaminase (ADA) on pleural fluid for diagnosis of tuberculous (TB) pleurisy within different age groups. Methods: The data of patients with pleural effusion from the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from April 2012 to November 2016 were retrospectively analyzed, and the diagnoses of these patients were histopathologically confirmed through medical thoracoscopy. The cases who had confirmed diagnosis, in the same time, received peripheral blood T-SPOT.TB were enrolled. The performance of peripheral blood T-SPOT.TB in combination with pleural fluid ADA on diagnosing TB pleurisy in the younger patients (16-59 years old) and elderly patients (≥60 years old) were analyzed respectively. The sensitivity, specificity and the receiver operating characteristic (ROC) curve were adopted for statistical analysis. Results: A total of 448 cases were finally enrolled, 341(76.1%) confirmed with TB pleurisy, 224 males, 117 females, (47±19) years old; and 107 (23.9%) classified as non-TB pleurisy, 65 males, 42 females, (61±14) years old. There were 285 cases who were classified as younger group, and the other 163 cases were classified as elderly group. The sensitivity and specificity of peripheral blood T-SPOT.TB were 85.4% (204/239) and 71.7% (33/46) in the younger patients, 76.5% (78/102) and 59.0% (36/61) respectively in the elderly patients. The sensitivity of peripheral blood T-SPOT.TB in the younger patients was significantly higher than that in the elderly patients (P=0.047). The sensitivity and specificity were 99.2% and 95.7% in combination with peripheral blood T-SPOT.TB and pleural fluid ADA respectively in the younger patients. The area under ROC curve (AUC) of T-SPOT.TB in the younger patients was 0.833, AUC of T-SPOT.TB combined with ADA was 0.911. The combination test of 2 tests had the sensitivity of 96.1% and the specificity of 90.2% respectively in the elderly patients. The AUC of T-SPOT.TB in the elderly patients was 0.747, AUC of T-SPOT.TB combined with ADA was 0.911. Conclusion: Peripheral blood T-SPOT.TB combined with pleural fluid ADA can improve the diagnostic performance for TB pleurisy with different ages, especially for elderly patients who can't tolerate pleural biopsy.


Asunto(s)
Adenosina Desaminasa/análisis , Tuberculosis Pleural/diagnóstico , Adulto , Anciano , Biopsia , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pleura , Derrame Pleural , Curva ROC , Sensibilidad y Especificidad
12.
Clin Microbiol Infect ; 22(2): 201-207, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26493847

RESUMEN

Finite treatment with nucleos(t)ide analogues (NAs) remains a great challenge for chronic hepatitis B in the clinic. This study aimed to investigate the relationship between intrahepatic quasispecies heterogeneity and the NAs off-treatment outcomes in a prospective cohort. Eighteen HBeAg-positive patients with chronic hepatitis B who achieved the cessation criteria underwent liver biopsy, and stopped treatment thereafter. Patients were followed up prospectively for 1 year. The reverse transcriptase (RT) gene of intrahepatic hepatitis B virus (HBV) was cloned and sequenced. Intrahepatic quasispecies heterogeneity and specific gene mutations were analysed using bioinformatic methods. Ten patients achieved sustained response, and eight patients developed viral relapse. The intrahepatic quasispecies Shannon entropy and nucleotide diversity within either RT or the surface (S) region of patients with sustained response were significantly higher (p < 0.05) than those of patients who had a viral relapse. Intrahepatic quasispecies Shannon entropy at the nucleotide level predicted the sustained off-treatment response (area under receiver operating characteristics curve 0.925; 95% CI 0.807-1.000; p 0.003). More positive selection sites and N-glycosylation mutations within the S region were found in patients with sustained response than in the patients with viral relapse (p < 0.01). Most of the positive selection sites in patients with sustained response were located in reported HLA-I-restricted or HLA-II-restricted epitopes. Intrahepatic quasispecies heterogeneity at the end of treatment was correlated with off-treatment outcomes in HBeAg-positive patients with chronic hepatitis B. More immune escape mutations were found within the S region in patients with sustained response. The higher intrahepatic quasispecies heterogeneity indicated a more robust immune control over HBV, which in turn maintained a sustained response after withdrawal of NAs.


Asunto(s)
Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/metabolismo , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Nucleósidos/uso terapéutico , ADN Polimerasa Dirigida por ARN/genética , Adulto , Clonación Molecular , Femenino , Heterogeneidad Genética , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/enzimología , Hepatitis B Crónica/metabolismo , Hepatitis B Crónica/virología , Humanos , Hígado/virología , Masculino , Mutación , Estudios Prospectivos , Recurrencia , Resultado del Tratamiento , Adulto Joven
13.
Cell Death Dis ; 2: e185, 2011 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-21796157

RESUMEN

The use of celecoxib is associated with a significant decrease in breast cancer risk. However, the long-term use of high-dose celecoxib might be limited owing to cardiovascular side effects. In this study, we found that acetylbritannilactone (ABL), extract from a Chinese medicinal herb, could reduce celecoxib dose and potentiate the growth-inhibitory effect in breast cancer cells. ABL enhanced the apoptotic effect of celecoxib in COX-2-expressing cells, but had little effect in COX-2-negative cells. The apoptosis induced by the combination treatment disappeared when COX-2 was knocked down, whereas the lack of apoptotic effects in COX-2-negative cells was reversed after COX-2 transfection. However, the combination treatment induced a G(0)/G(1) phase arrest independent of whether or not the cells expressed COX-2. The G(0)/G(1) arrest was attributed to a decreased expression of cyclinD1, cyclinE, CDK2 and CDK6, especially the upregulation of p21. In addition, inhibition of Akt and p38 signaling pathways was required by the synergism, as the constitutively active Akt and p38 protected cells against apoptosis and cell cycle arrest induced by the combination treatment. In vivo, administration of celecoxib and ABL were more effective than the individual agents against xenograft tumor growth. Thus, our data suggested that the combinatorial approach of celecoxib and ABL might be helpful for breast cancer treatment.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/toxicidad , Ciclooxigenasa 2/metabolismo , Medicamentos Herbarios Chinos/toxicidad , Lactonas/toxicidad , Pirazoles/toxicidad , Sulfonamidas/toxicidad , Animales , Apoptosis/efectos de los fármacos , Celecoxib , Línea Celular Tumoral , Ciclina D1/metabolismo , Ciclina E/metabolismo , Quinasa 2 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Ciclooxigenasa 2/química , Ciclooxigenasa 2/genética , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Fase G1 , Humanos , Lactonas/uso terapéutico , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirazoles/uso terapéutico , Fase de Descanso del Ciclo Celular , Transducción de Señal , Sulfonamidas/uso terapéutico , Trasplante Heterólogo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
14.
J Exp Clin Cancer Res ; 25(4): 575-83, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17310849

RESUMEN

Nucleostemin (NS) is preferentially and exclusively expressed in the stem cells and cancer cells, but not in differentiated adult tissues and cells. NS is likely to take part in controlling the proliferation and differentiation switch in stem cells and progenitor cells. Its deregulation in cancer also contributes to the elevated proliferation and undifferentiation of cancer cells. However, the mechanisms by which NS helps to maintain both cancer and stem cells in undifferentiated state remain unclear. In this study, we carried out gene profilings using oligonucleotide DNA microarray after knocking down the expression of NS in Hela cells. Of the 21,329 genes, 200 genes were found differentially expressed in NS silenced Hela cells with > 2 fold ratio (either > 2 or < 0.5). Category analysis indicated these differential genes were mainly related with cancer pathogenesis, cell death, cell growth and proliferation. NS related gene pathway analysis suggested NS was mostly involved in the networks of cell cycle and differentiation controls. p53 may not be the only partner of NS in its regulated pathways. c-Myc may directly or indirectly interact with it to control the proliferation and differentiation switch in cancer cells. Our study provides a general view of the NS-target genes, and indicates the possible pathways in which NS plays its role in proliferation control.


Asunto(s)
Proteínas Portadoras/genética , Perfilación de la Expresión Génica , Proteínas Nucleares/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas de Unión al GTP , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Hibridación de Ácido Nucleico , Oligodesoxirribonucleótidos , ARN Interferente Pequeño/genética
15.
Proc Natl Acad Sci U S A ; 97(26): 14754-9, 2000 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-11114157

RESUMEN

Retinoic acid (RA), a signaling molecule derived from vitamin A, controls growth and differentiation of a variety of cell types through regulation of gene transcription. In the vertebrate retina, RA also regulates gap junction-mediated physiological coupling of retinal neurons through a nontranscriptional mechanism. Here we report that RA rapidly and specifically modulates synaptic transmission at electrical synapses of cultured retinal horizontal cells through an external RAR(beta)(/gamma)-like binding site, the action of which is independent of second messenger cascades. External application of all-trans retinoic acid (at-RA) reversibly reduced the amplitude of gap junctional conductance in a dose-dependent manner, but failed to affect non-gap-junctional channels, including glutamate receptors. In contrast, internal dialysis with at-RA was ineffective, indicating an external site of action. Selective RAR(beta)(/gamma) ligands, but not an RAR(alpha)-selective agonist, mimicked the action of at-RA, suggesting that gating of gap junctional channels is mediated through an RAR(beta)(/gamma)-like binding site. At-RA did not act on gap junctional conductance by lowering [pH](i) or by increasing [Ca(2+)](i). A G protein inhibitor and protein kinase inhibitors did not block at-RA uncoupling effects indicating no second messenger systems were involved. Direct action of at-RA on gap junction channels was further supported by its equivalent action on whole-cell hemi-gap-junctional currents and on cell-free excised patch hemichannel currents. At-RA significantly reduced single-channel open probability but did not change unitary conductance. Overall, the results indicate that RA modulates horizontal cell electrical synapses by activation of novel nonnuclear RAR(beta)(/gamma)-like sites either directly on, or intimately associated with, gap junction channels.


Asunto(s)
Uniones Comunicantes/fisiología , Retina/fisiología , Sinapsis/fisiología , Tretinoina/análogos & derivados , Tretinoina/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Lubina , Células Cultivadas , Electrofisiología , Uniones Comunicantes/efectos de los fármacos , Glucurónidos/metabolismo , Guanosina Trifosfato/metabolismo , Receptores de Ácido Retinoico/metabolismo , Retina/citología , Receptor alfa de Ácido Retinoico , Tretinoina/farmacología
16.
J Neuroimmunol ; 108(1-2): 201-6, 2000 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-10900354

RESUMEN

We analyzed the effects of glatiramer acetate (GA) therapy on in vitro proliferative responses and cytokine production by lymphocytes derived from multiple sclerosis patients receiving this therapy. We confirmed that lymphocytes derived from GA naïve patients show a high frequency of response when initially exposed to GA in vitro; this frequency decreased following GA therapy. The frequency of lymphocytes responding to whole MBP stimulation did not change with GA therapy. GA- and MBP-specific T cell lines generated from these patients by repeated cycles of in vitro stimulation did not cross react. Some (23%) whole MBP-reactive T cell lines did cross react with MBP peptide 83-99. The mean levels of interferon (IFN) gamma secretion and the mean ratio of IFN-gamma/IL-5 were lower for GA-reactive cell lines, derived from patients both prior to and during GA therapy, compared to MBP-reactive T cell lines. The proportion of IFN-gamma(+) cells in unfractionated lymphocyte preparations derived from the GA-treated patients did not differ from that found for healthy controls. Our findings indicate that GA-reactive T cell lines derived from GA-treated MS patients continue to show a relative Th2 cytokine bias consistent with a bystander suppressor function. GA treatment is not associated with a cytokine phenotype shift in the total T cell or MBP-reactive T cell populations.


Asunto(s)
Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Péptidos/farmacología , Péptidos/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Adulto , División Celular/efectos de los fármacos , Células Cultivadas , Ensayos Clínicos Controlados como Asunto , Método Doble Ciego , Femenino , Acetato de Glatiramer , Humanos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Interferón gamma/biosíntesis , Interferón gamma/metabolismo , Interleucina-10/biosíntesis , Interleucina-10/metabolismo , Interleucina-5/biosíntesis , Interleucina-5/metabolismo , Recuento de Linfocitos/efectos de los fármacos , Masculino , Esclerosis Múltiple/patología , Proteína Básica de Mielina/inmunología , Linfocitos T/metabolismo , Células Th2/efectos de los fármacos , Células Th2/inmunología , Células Th2/metabolismo , Factores de Tiempo
18.
Chin Med J (Engl) ; 106(9): 659-64, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8287699

RESUMEN

The changes in 15 cases of viral myocarditis and 28 cases of dilated cardiomyopathy were reported and compared, which were the pathological changes of endomyocardial biopsy; NK cells activity; % of peripheral T lymphocytes and its subsets determined by using OKT3,4,8 (OKT3-peripheral total lymphocytes; OKT4-helper cells; OKT8-suppressive cells) monoclonal antibody; values of immunoglobulin IgG, IgA, IgM; titer of coxsackie B antibody neutralization test. And a discussion on their relationship was included.


Asunto(s)
Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Dilatada/patología , Infecciones por Coxsackievirus , Enterovirus Humano B , Miocarditis/inmunología , Miocarditis/patología , Adolescente , Adulto , Anticuerpos Antivirales/análisis , Enterovirus Humano B/inmunología , Femenino , Humanos , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Miocarditis/microbiología , Miocardio/ultraestructura , Subgrupos de Linfocitos T/inmunología
19.
Int J Pept Protein Res ; 37(5): 457-61, 1991 May.
Artículo en Inglés | MEDLINE | ID: mdl-1917301

RESUMEN

The same dialkylphosphite reagent can be used for both N protection and C activation of amino acids. Two N-diisopropyloxyphosphinyl (Dipp) tripeptide esters were prepared, and nine N-Dipp-dipeptide acids were synthesized through the activated amide intermediate. The positive ion FAB-MS of N-Dipp-tripeptide showed novel cleavage patterns in that only the N-phosphoryl fragment ions gave intense peaks while the C-terminal series ions did not appear. This novel character might be useful for peptide sequence analysis. In addition, dialkyloxyphosphinyl group can be examined by 31P-NMR for peptide conformational analysis and inspection for the degree of racemization during the coupling reaction.


Asunto(s)
Péptidos/síntesis química , Secuencia de Aminoácidos , Espectroscopía de Resonancia Magnética/métodos , Datos de Secuencia Molecular , Ácidos Fosforosos , Espectrometría de Masa Bombardeada por Átomos Veloces , Tiazoles , Tiazolidinas
20.
Zhonghua Yan Ke Za Zhi ; 25(4): 200-2, 1989 Jul.
Artículo en Chino | MEDLINE | ID: mdl-2620612

RESUMEN

Fundus examination of 255 newborns in high altitude Tibet revealed that the optic discs were of orange-pink colour with clear margin and over ten small vessels. The C/D ratio in 500 eyes (98.04%) was 0.3 or less, and none was 0.6 or over. The C/D ratio in both eyes of 242 babies (94.90%) was symmetrical and in only 1 case (0.39%) it differed by 0.2. The macula of all infants was dark red with no foveal reflection. Some of the veins were engorged. Retinal hemorrhages were found in 64 cases (25.10%), 12 cases in the macular region and 1 case on the optic disc. Retinal edema was present in 30 cases, cotton wool exudates in 30 cases, vitreous artery in 6 cases, and congenital cataracts in 1 case. The mechanism of retinal changes were discussed.


Asunto(s)
Angiografía con Fluoresceína , Mácula Lútea/anatomía & histología , Edema Macular/epidemiología , Tamizaje Neonatal , Hemorragia Retiniana/epidemiología , Altitud , China/epidemiología , Femenino , Humanos , Recién Nacido , Edema Macular/etiología , Masculino , Disco Óptico/anatomía & histología , Hemorragia Retiniana/etiología
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