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1.
Zhonghua Zhong Liu Za Zhi ; 46(5): 428-437, 2024 May 23.
Artículo en Zh | MEDLINE | ID: mdl-38742356

RESUMEN

Objective: This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer. Methods: A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness. Results: The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model (P<0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model (P<0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort (P<0.05) and was better than that of DCE-2 and ADC models in the validation cohort (P<0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions: T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.


Asunto(s)
Neoplasias de la Mama , Imagen por Resonancia Magnética , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Receptor ErbB-2/metabolismo , Imagen por Resonancia Magnética/métodos , Curva ROC , Radiómica
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(5): 507-511, 2023 May 12.
Artículo en Zh | MEDLINE | ID: mdl-37147815

RESUMEN

Airway stents are commonly used to treat patients with central airway obstruction, but several complications have been identified, including mucus plugging, granulation tissue, stent migration, and infection. Stent associated respiratory tract infection (SARTI) has often been neglected by the practicing clinicians. Therefore, we reviewed the available current literatures on the diagnosis and management of stent associated respiratory tract infection.


Asunto(s)
Obstrucción de las Vías Aéreas , Infecciones del Sistema Respiratorio , Humanos , Broncoscopía , Stents/efectos adversos , Obstrucción de las Vías Aéreas/etiología
3.
Zhonghua Zhong Liu Za Zhi ; 43(2): 228-232, 2021 Feb 23.
Artículo en Zh | MEDLINE | ID: mdl-33601490

RESUMEN

Objective: To provide the risk stratification method of hepatoblastoma (HB) suitable for implementation in China and explore the new treatment method for high-risk HB patients. Methods: A total of 100 cases of children and adolescents under 18 years old with newly diagnosed HB in Sun Yat-sen University Cancer Center and Sun Yat-sen University First Affiliated Hospital from September 2014 to September 2018 were included. According to the clinical stage, AFP level, pathological subtype and other factors, patients were stratified into four groups: extremely low-, low-, intermediate- and high-risk. The patients at very low risk were treated with surgery only and followed-up. The patients at very low risk were treated with C5V(Cisplatin+ 5-Fluroracil+ Vincristine) regimen for 4 courses. The patients at intermediate risk were treated with C5VD(Cisplatin+ 5-Fluroracil+ Vincristine+ Doxorubicin)regimen before and after surgery for 6-8 courses. The patients at high risk were treated with C5VD and IIV (ifoshamide+ irinotecan+ vincristine) alternately before and after surgery for 8 courses. Results: One hundred patients were stratified into extremely low-risk, low-risk, medium-risk and high-risk groups for 2, 10, 51 and 37 cases, respectively. Eighty three cases had evaluable lesions before chemotherapy. Among them, 65 patients achieved partial remission, stable disease and progressive disease were observed in 10, and 8 cases, respectively, with a response rate of 78.3%. During a median follow-up of 20 months, 30 patients experienced tumor relapse or progression, and 27 of them died. The 2-years progression-free survival (PFS) and overall survival (OS) rates were 69.2% and 72.0%, respectively. The 2-years PFS rates of patients with extremely low risk, low risk, medium risk and high risk were 100%, 88.9%, 75.3% and 43.2%, respectively. The 2-years OS rates were 100%, 100%, 81.0% and 44.8%, respectively. Conclusions: The novel HB risk classification is simple and feasible. With active comprehensive treatment, patients at extremely low-, low- and medium-risk have excellent outcomes. The survival rate of high-risk HB patients remains to be improved, and new treatment strategies need to be explored.


Asunto(s)
Hepatoblastoma , Neoplasias Hepáticas , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , China , Doxorrubicina/uso terapéutico , Hepatoblastoma/tratamiento farmacológico , Hepatoblastoma/cirugía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia , Medición de Riesgo , Resultado del Tratamiento , Vincristina
4.
Zhonghua Yi Xue Za Zhi ; 98(20): 1582-1587, 2018 May 29.
Artículo en Zh | MEDLINE | ID: mdl-29886649

RESUMEN

Objective: Using clinical "big data" , to investigate the factors that affect the levels of thyroid hormones, and to explore the partitioning criteria for reference intervals (RI) of these hormones. Methods: An observation study was conducted. Information of 107 107 individuals undergoing routine physical examination in Peking Union Medical College Hospital from September 1(st,) 2013 to August 31(st,) 2016 was collected, thyroid hormone of these subjects were detected. To explore the test results distribution and differences of TSH, FT4 and FT3 by gender and age; according to the seasonal division standard of China Meteorological Administration, the study period was divided into four seasons, and the seasonal fluctuation on TSH was analyzed.To define the appropriate partition by gender, age and season according to significant difference analysis. Results: In male and female, the distributions of TSH were 1.779(0.578-4.758), 2.023(0.420-5.343)mU/L, respectively, and the level of TSH in female was higher than in male (Z=-37.600, P<0.001). The distributions of FT4 were 0.127(0.098-0.162), 0.117(0.091-0.151) µg/L, the distributions of FT3 were 3.33(2.47-3.74), 3.01(2.35-3.57)ng/L. And the level of FT4, FT3 in female were significantly lower than in male (Z=-94.000, -154.600, all P<0.001). Furthermore, males were divided into two groups by 65 years old and female were divided by 50 years old, respectively, and the distributions of TSH in male and female of older group were 1.818(0.528-5.240), 2.111(0.348-5.735)mU/L, in younger group were 1.778(0.582-4.696), 1.991(0.427-5.316)mU/L. The level of TSH in older group was significantly higher than in younger group (Z=-2.269, -10.400, all P<0.05), and the distribution of TSH in older group was much wider than in younger. The distribution of whole in spring, summer and autumn was 1.869( 0.510-5.042)mU/L, in winter was 1.978(0.527-5.250) mU/L, and the difference between them had statistical significance (Z=-15.000, P<0.001). Conclusions: Gender and age significantly affect the serum levels of TSH, FT4, and FT3, the distribution of TSH in female and elder group are wider than in male, and that of FT4, FT3 are lower.Seasons significantly affect the serum TSH level, the peak value is observed in winter. There are obviously differences between "rough" RIs and manufacture recommended RIs. Each laboratory should establish reference intervals for thyroid hormones on the premise of appropriate grouping.


Asunto(s)
Hormonas Tiroideas/análisis , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Estaciones del Año , Pruebas de Función de la Tiroides
5.
Gene Ther ; 22(10): 793-801, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26005859

RESUMEN

Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer.


Asunto(s)
Terapia Genética , Vectores Genéticos , Lentivirus , Neoplasias Gástricas/genética , Proteínas Supresoras de Tumor/genética , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Ratones , Ratones Desnudos , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Proteínas Supresoras de Tumor/biosíntesis
6.
Anal Biochem ; 473: 1-6, 2015 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25524617

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) can form DNA-binding compounds that show genotoxicity and carcinogenicity. Pyrene, as a PAH, was covalently linked to carrier protein bovine serum albumin and ovalbumin. A monoclonal antibody (McAb) was produced that showed high cross-reactivity values with chrysene (169.73%), benzo[a]pyrene (693.34%), benzo[a]anthracene (16.36%), and indeno[1,2,3-cd]pyrene (40.96%) and showed no significant cross-reactivity values with other homologues (<0.1%). A competitive enzyme-linked immunosorbent assay (ELISA) was developed for detection of pyrene and some homologues in water samples. The detection limit of the assay was 65.08 pg ml(-1). The average recoveries of PAHs from tap water, lake water, and mineral water were 99.13, 99.74, and 99.19%, respectively, indicating that matrices of water samples do not interfere with the assay. The results demonstrated that the developed ELISA seems to be a potential method for monitoring of pyrene and some homologous PAHs in water samples.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Pirenos/análisis , Animales , Anticuerpos Monoclonales/inmunología , Calibración , Bovinos , Reacciones Cruzadas , Límite de Detección , Modelos Lineales , Ovalbúmina/química , Pirenos/química , Pirenos/inmunología , Albúmina Sérica Bovina/química , Agua/química
7.
Genet Mol Res ; 13(2): 2343-8, 2014 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-24781989

RESUMEN

Ulcerative colitis (UC) is a chronic inflammation of the large intestine. The aim of this study was to investigate the association of two polymorphisms in STAT3 with the risk of UC development in the Chinese Han population. This is a hospital-based case-control study involving 56 UC patients and 274 controls. Genotyping was performed using the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. Statistical analyses were conducted using logistic regression and genotype risk score. Overall, there was a significant difference between patients and controls in the genotype distribution of rs2293152 (P = 0.044). The risk for UC associated with the rs2293152-G mutant allele was increased (odds ratio = 2.76; 95% confidence interval = 1.06- 7.24) under the dominant model. However, we failed to find any obvious differences in the rs4796793 genotype or allele distributions between the UC patients and controls, and did not detect any significant association of the rs4796793 polymorphism with UC across different genetic models of inheritance. Our study implies that the STAT3 rs2293152 polymorphism may be associated with the occurrence of UC and might be used as a predictive factor for UC in the Chinese Han population.


Asunto(s)
Colitis Ulcerosa/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Factor de Transcripción STAT3/genética , Adolescente , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Colitis Ulcerosa/patología , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
8.
Genet Mol Res ; 12(2): 1511-21, 2013 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-23765957

RESUMEN

Hereditary deficiency of factor VIII (FVIII) leads to hemophilia A, a severe X-linked bleeding disorder. Current therapies include fixed-dose FVIII prophylaxis, factor replacement therapy, and most recently, gene therapy. Prophylaxis and FVIII replacement therapies are limited by incomplete efficacy, high cost, restricted availability, and development of neutralizing antibodies in chronically treated individuals. Limited success has been obtained in preclinical trials using gene therapy for the treatment of hemophilia. Therefore, new options for therapy for hemophilia A are needed. We evaluated the potential of embryonic stem cells for correcting hemophilia A in mice. FVIII-deficient mouse blastocysts were collected and injected with mouse embryonic stem cells stably expressing green-fluorescent protein (GFP) and transferred to pseudopregnant recipient mice. Expression of FVIII was measured in the liver and plasma of the 5 chimeric mice that were produced. Three of these mice were GFP-positive at the age of 6 months. The plasma FVIII activity levels were equal to those of wild-type mice. These data demonstrate that embryonic stem cell transplantation at an early embryonic stage has potential as therapy for this progressively debilitating, life-threatening bleeding disorder.


Asunto(s)
Células Madre Embrionarias/citología , Factor VIII/metabolismo , Hemofilia A/terapia , Trasplante de Células Madre , Animales , Quimera , Células Madre Embrionarias/metabolismo , Factor VIII/genética , Femenino , Proteínas Fluorescentes Verdes/metabolismo , Hemofilia A/sangre , Humanos , Inmunohistoquímica , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Transgénicos , Microscopía Fluorescente , Fenotipo
9.
Zhonghua Nei Ke Za Zhi ; 57(4): 302-305, 2018 Apr 01.
Artículo en Zh | MEDLINE | ID: mdl-29614593
10.
Zhonghua Xue Ye Xue Za Zhi ; 43(5): 400-407, 2022 May 14.
Artículo en Zh | MEDLINE | ID: mdl-35680598

RESUMEN

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/farmacología , Enfermedad Injerto contra Huésped/metabolismo , Humanos , Células Asesinas Naturales , Estudios Retrospectivos , Resultado del Tratamiento
11.
Clin Exp Immunol ; 165(2): 264-77, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21635226

RESUMEN

Regulatory T cells (T(regs) ) play a key role in the prevention of acute graft-versus-host disease (aGVHD). To investigate the association between T(reg) subsets and aGVHD, we prospectively analysed T cell subsets in the allografts of 35 patients undergoing myeloablative unmanipulated haematopoietic stem cell transplantation. Multivariate analysis found that patients infused with less than 0·29 × 10(6) /kg of CD4(+) CD25(high) CD45RA(+) CD62L(+) T cells during transplantation exhibited an increased incidence of II-IV aGVHD [hazard ratio (HR) = 0·000, 95% CI = 0·000-0·106, P = 0·013]. Next, we compared the reconstitution characteristics of T cell subsets between haploidentical haematopoietic stem cell transplantation (HSCT) and sibling HSCT by collecting peripheral blood samples at regular intervals (days 30, 60 and 90) after transplantation. No significant differences were observed in the reconstitution of conventional T cells between haploidentical HSCT and sibling identical HSCT. However, total counts of recovered naiveT(regs) and CD62L(+) naive T(regs) from haploidentical HSCT were significantly lower compared to sibling identical HSCT; P-values were 0·045 and 0·021, respectively. Although total counts of conventional T cells in aGVHD patients reached similar levels compared to non-aGVHD patients before day 60 post-HSCT, total counts of naive T(regs) and CD62L(+) naive T(regs) in aGVHD patients did not reach similar levels to non-aGVHD patients until 90 days post-HSCT. Taken together, our findings demonstrate that a large population of CD62L(+) naive T(regs) in allografts reduces the incidence of aGVHD. Further, development of aGVHD is related closely to the delayed reconstitution of the naive T(reg) population.


Asunto(s)
Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Antígenos CD4/análisis , Niño , Femenino , Factores de Transcripción Forkhead/análisis , Humanos , Subunidad alfa del Receptor de Interleucina-2/análisis , Selectina L/análisis , Antígenos Comunes de Leucocito/análisis , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Trasplante Homólogo
12.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 649-654, 2020 Aug 14.
Artículo en Zh | MEDLINE | ID: mdl-32942818

RESUMEN

Objective: To summarize the efficiency and long-term outcomes of limited-stage Hodgkin lymphoma in children and adolescents with ABVD therapy and determined whether omitting radiotherapy for a low-risk patient enabled the achievement of complete response (CR) after chemotherapy. Methods: We retrospectively analyzed data from 13 y (2004-2016) from patients aged ≤18 y with limited-stage HL admitted to the Sun Yat-sen University Cancer Center. Patients received treatment with ABVD chemotherapy alone or ABVD chemotherapy followed by low-dose involved field radiotherapy. Results: Total 85 subjects were eligible for study inclusion; the median age was 12 (3-18) y; 66 (77.6%) were men, 80 (94.1%) had stage-II disease, 56 (65.9%) were at low-risk, and the median follow-up duration was 72 (8-196) months; 12 relapsed, 2 had secondary neoplasm, and 2 died. The 5-year event free survival (EFS) was (85.6±3.8) %, and the overall survival (OS) was 100%. The 5-year EFS and OS was (89.1±4.2) % and 100%, respectively, for the low-risk cohort and (79.3±7.5) % and 100%, respectively for the intermediate-risk cohort. Among the 39 low-risk patients who achieved CR after chemotherapy, 15 received treatment with chemotherapy followed by LD-IFRT. In the exploratory subset analysis, the low-risk cohort who achieved CR after chemotherapy, the 5-year EFS for comparing ABVD alone with chemotherapy followed by LD-IFRT was (87.0±7.0) % versus 100% (P=0.506) , and the OS was 100% for both the groups. Conclusions: Our retrospective analysis showed excellent survival of limited-stage HL patients with ABVD therapy. For patients who achieving CR after chemotherapy with low-risk HL, received chemotherapy followed by LD-IFRT does not improve 5-year OS and EFS. The use of risk- and response-based stratification may facilitate the development of effective and less toxic protocols.


Asunto(s)
Enfermedad de Hodgkin , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Niño , Preescolar , Dacarbazina , Supervivencia sin Enfermedad , Doxorrubicina , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del Tratamiento , Vinblastina
13.
Placenta ; 30(3): 226-35, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19168217

RESUMEN

The human (h) growth hormone/chorionic somatomammotropin (GH/CS) gene locus presents a unique model to gain insight into the molecular mechanisms that have allowed a closely related family of genes to be expressed in two distinct cell lineages/tissues: pituitary somatotrophs and placental syncytiotrophoblasts. However, studies of external factors that regulate gene expression have been somewhat limited by (i) a lack of human cell lines expressing endogenous GH or CS appropriately; and (ii) the fact that the GH/CS locus is unique to primates and thus does not exist in rodents. In the current study, a transgenic (171 h GH/CS-TG) mouse was generated containing the intact hGH/CS gene cluster and hGH locus control region (LCR) in a 171-kilobase DNA fragment. Pituitary and placental-specific expression of hGH/CS RNA was detected at embryonic day (E) 18.5. Immunostaining of hGH was seen in somatotrophs of the anterior pituitary beginning in late gestation. The presence of hCS protein was detected in the placental labyrinth in trophoblasts functionally analogous to the syncytiotrophoblast of the chorionic villi. This pattern of gene expression is consistent with the presence of essential components of the hGH/CS LCR. Transcript levels for hCS-A, hCS-B and placental hGH-variant increased in 171 hGH/CS-TG placenta during gestation (E11.5-E18.5), as previously observed in human placental development. Throughout gestation, hCS-A RNA levels were proportionately higher, accounting for 91% of total CS RNA by E18.5, comparable to term human placenta. Finally, the previous correlation between the transcription factor AP-2alpha and hCS RNA expression observed in developing primary human cytotrophoblast cultures, was extended to pregnancy in the 171 hGH/CS-TG mouse. The 171 hGH/CS-TG mouse thus provides a model to investigate hGH/CS gene expression, including in pregnancy.


Asunto(s)
Hormona de Crecimiento Humana/metabolismo , Región de Control de Posición , Placenta/metabolismo , Lactógeno Placentario/metabolismo , Preñez/metabolismo , Animales , Antígenos CD79/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Hormona de Crecimiento Humana/genética , Humanos , Ratones , Ratones Transgénicos , Canal de Sodio Activado por Voltaje NAV1.4 , Hipófisis/metabolismo , Lactógeno Placentario/genética , Embarazo , Canales de Sodio/genética , Factor de Transcripción AP-2/metabolismo , Transgenes
14.
Clin Genet ; 75(5): 480-4, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19475720

RESUMEN

The mitochondrial 1555A>G mutation is one of the most common mutations responsible for hearing loss in Asians. Although the association with aminoglycoside exposure is well known, there is great variation in the severity of hearing loss. We analyzed hearing levels in 221 Japanese individuals with this mutation and attempted to identify relevant covariants including (i) age, (ii) aminoglycoside exposure, (iii) heteroplasmy ratio, and (iv) other gene mutations. At every age, average hearing levels were worse than those in normal subjects, suggesting that mitochondrial function itself may affect the severity of hearing loss. Although the hearing loss in individuals with the 1555A>G mutation progressed with age, the rate did not differ from that of the normal subjects. Those who had reported aminoglycoside exposure had moderate-to-severe hearing impairment regardless of age, confirming that such exposure is the most important environmental variable. We also confirmed the presence of heteroplasmy, which is known to modify the expression of other mitochondrial diseases, but found no evidence for a significant correlation with hearing impairment. A high prevalence of GJB2 heterozygous mutations was noted, indicating that these mutations may exhibit epistatic interaction with the 1555A>G mutation.


Asunto(s)
ADN Mitocondrial/química , Pérdida Auditiva/genética , Mutación Puntual , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Conexina 26 , Conexinas , Audición/genética , Pérdida Auditiva Sensorineural/genética , Heterocigoto , Humanos , Persona de Mediana Edad , Prevalencia
15.
Plant Biol (Stuttg) ; 10(3): 323-33, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18426479

RESUMEN

Salidroside, a novel effective adaptogenic drug extracted from the medicinal plant Rhodiola sachalinensis A. Bor, can be derived from phenylalanine or tyrosine. Due to the scarcity of R. sachalinensis and its low yield of salidroside, there is great interest in enhancing production of salidroside by the plant. In this study, a cDNA clone encoding phenylalanine ammonia-lyase (PAL) was isolated from R. sachalinensis using rapid amplification of cDNA ends. The resulting cDNA was designated PALrs1. It is 2407-bp long and encodes 710 deduced amino acid residues. Southern blot analysis of genomic DNA indicated that the PAL gene family is composed of three to five genes in the R. sachalinensis genome. Northern blot analysis revealed that transcripts of PALrs1 were present in calli, leaves and stems, but expression in roots was very low. The PALrs1 under the 35S promoter with double-enhancer sequences from CaMV-Omega and TMV-Omega fragments was transferred into R. sachalinensis via Agrobacterium tumefaciens. PCR and PCR-Southern blot confirmed that the PALrs1 gene had been integrated into the genome of transgenic plants. Northern blot analysis revealed that the PALrs1 gene had been expressed at the transcriptional level. High-performance liquid chromatography indicated that overexpression of the PALrs1 gene resulted in a 3.3-fold increase in p-coumaric acid content, as expected. In contrast, levels of tyrosol and salidroside were 4.7-fold and 7.7-fold, respectively, lower in PALrs1 transgenic plants than in controls. Furthermore, overexpression of the PALrs1 gene resulted in a 2.6-fold decrease in tyrosine content. These data suggest that overexpression of the PALrs1 gene and accumulation of p-coumaric acid did not facilitate tyrosol biosynthesis; tyrosol, as a phenylethanoid derivative, is not derived from phenylalanine; and reduced availability of tyrosine most likely resulted in a large reduction in tyrosol biosynthesis and accumulation of salidroside.


Asunto(s)
Glucósidos/biosíntesis , Fenilanina Amoníaco-Liasa/metabolismo , Alcohol Feniletílico/análogos & derivados , Rhodiola/metabolismo , Secuencia de Aminoácidos , Ácidos Cumáricos/metabolismo , Expresión Génica , Datos de Secuencia Molecular , Familia de Multigenes , Fenoles , Fenilanina Amoníaco-Liasa/genética , Alcohol Feniletílico/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Propionatos , Rhodiola/enzimología , Rhodiola/genética , Análisis de Secuencia de ADN , Tirosina/metabolismo
16.
J Hazard Mater ; 151(2-3): 522-30, 2008 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-17640802

RESUMEN

The concentrations of 17PCDD/F congeners as well as tetra- to octa-homologues were determined in 33 soil samples collected within a radius of 7 km from a municipal solid waste (MSW) incineration plant that is equipped with three fluidized bed incinerators (FBIs) of co-firing MSW with coal in Hangzhou, China. The total PCDD/F concentrations ranged from 0.39 to 5.04 pg I-TEQ g(-1) (54-285 pg g(-1)), with an average and a median value of 1.22 and 0.84 pg I-TEQ g(-1) (105 and 86 pg g(-1)), respectively. A systematic decrease of PCDD/F levels was observed with the increasing distances and with the decreasing downwind frequencies from the plant. The comparisons of homologue and congener patterns and multivariate analysis of soil and flue gas samples strongly indicated that most of the soil samples were influenced by the FBIs. Apart from the incineration plant, historical PCDD/F emissions of hazardous waste incinerator (HWI) and motor vehicles as well as the application of 1,3,5-trichloro-2-(4-nitrophenoxy) benzene (CNP) seemed to play an important role in soil samples adjacent to these potential sources.


Asunto(s)
Benzofuranos/análisis , Carbón Mineral/análisis , Monitoreo del Ambiente/métodos , Dibenzodioxinas Policloradas/análogos & derivados , Contaminantes del Suelo/análisis , Agricultura , China , Dibenzofuranos Policlorados , Contaminación Ambiental , Incineración , Residuos Industriales , Dibenzodioxinas Policloradas/análisis , Eliminación de Residuos , Suelo/análisis , Contaminantes del Agua
17.
J Hazard Mater ; 150(3): 510-4, 2008 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-17574738

RESUMEN

Fly ash from municipal solid waste (MSW), medical waste (MW) and electrical power plant (EPP) incinerators were analyzed for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). The study showed that the PCDD/F levels in fly ash were EPP

Asunto(s)
Contaminantes Atmosféricos/análisis , Benzofuranos/análisis , Carbono/análisis , Material Particulado/análisis , Dibenzodioxinas Policloradas/análogos & derivados , China , Ceniza del Carbón , Dibenzofuranos Policlorados , Monitoreo del Ambiente , Incineración , Dibenzodioxinas Policloradas/análisis
18.
Zhonghua Xue Ye Xue Za Zhi ; 39(9): 734-738, 2018 Sep 14.
Artículo en Zh | MEDLINE | ID: mdl-30369183

RESUMEN

Objective: To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen. Methods: A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m(2) q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m(2) for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m(2) q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results: Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ(2)=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ(2)=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ(2)=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ(2)=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction. Conclusion: The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Aclarubicina , Adolescente , Adulto , Anciano , Citarabina/administración & dosificación , Decitabina/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
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