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1.
Mater Sci Eng C Mater Biol Appl ; 121: 111847, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579510

RESUMO

Targeted gene therapy has led to significant breakthroughs in cancer treatment. Heat shock protein gp96 is an emerging target for tumor treatment because of its transfer ability from reticulum to tumor cell surface. CDO14 is a peptide cationic liposome developed in our laboratory with higher gene transfection efficiency and lower toxicity compared with the existing cationic liposomes. In this study, gp96-targeted liposome p37-CDO14 was constructed by modifying cationic liposome CDO14 with a gp96 inhibitor, helical polypeptide p37. Liposome p37-CDO14 could specifically bind to breast cancer cells with gp96-overexpression on the cell membrane. Both liposomes CDO14 and p37-CDO14 showed high delivery efficiency for survivin siRNA (siSuvi) to SK-BR-3 and MCF-7 cells via obviously decreased survivin expression level and cell viability. P37-CDO14 significantly increased the accumulation of FAM-siRNA in tumor compared with CDO14. SiSuvi transfected by CDO14 and p37-CDO14 could inhibit the growth of xenograft in mice and the expression of survivin in tumor tissues. The anti-tumor effect of siSuvi delivered by p37-CDO14 was much higher than that delivered by CDO14. This suggests that targeted liposome p37-CDO14 is a potential gene vector for the therapy of gp96 overexpressed breast cancer.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 172-180, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554815

RESUMO

OBJECTIVE: To analyze clinical effectiveness of myelodysplastic syndrome (MDS) patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate new therapy strategy for the treatment of relapse after allo-HSCT. METHODS: 72 MDS patients treated by HSCT in our hospital from April 2013 to November 2019 were enrolled and analyzed retrospectively. The effect of allo-HSCT was summarized. The risk factors affecting the survival and relapse of the patients were investigated. RESULTS: Among 72 patients, the median follow up was 37(12-111) months. 57 patients survived(79.2%),while 15 patients died(20.8%). The 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were 76.6% and 62.3%, respectively. IPSS-R, TP53 mutation and chronic graft versus-host-disease (cGVHD) were the risk factors affecting the OS of the MDS patients after treated by allo-HSCT. IPSS-R, TP53 mutation and Ⅲ-Ⅳ° acute graft versus-host-disease (aGVHD) were the risk factors affecting the DFS of the MDS patients after treated by allo-HSCT. After transplanted, 19 patients (26.4%) emerged aGVHD, and 5 patients (6.9%) emerged Ⅲ-Ⅳ° aGVHD, 25 patients (34.7%) emerged cGVHD, while 4 patients (5.6%) emerged extensive cGVHD. 17 patients (23.3%) relapsed, and the 5-year cumulative incidence of relapse (CIR) rate was 27.5%. IPSS-R, TP53 mutation and cGVHD were the risk factors affecting the relapse of the patients. The median survival time after relapse was 9 months. There were 7 out of 17 relapsed patients survived without disease, while 10 patients died. The OS rate of patients treated with maintained hypomethylation agents(HMA) combined with G-CSF mobilized donor lymphocyte infusion (DLI) was significantly higher than the patients without HMA (80.0% vs 10.0%, P=0.002). CONCLUSION: Allo-HSCT is an effective therapy for intermediate and high risk MDS patients. But relapse after HSCT is still a major problem that affecting the survival of the patients. Maintenance treatment of HMA combined with DLI may improve the long-time survival of MDS patients with relapsed after treated by allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Estudos Retrospectivos , Resultado do Tratamento
3.
Bioconjug Chem ; 32(1): 73-81, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33393280

RESUMO

Multidrug resistance (MDR) is the main obstacle in cancer chemotherapy. ATP-binding cassette (ABC) transporters can transport a wide range of antitumor drugs out of cells, which is the most common reason in the development of resistance to drugs. Currently, various therapeutic strategies are used to reverse MDR, among which CRISPR/Cas9 gene editing technique is expected to be an effective way. Here, we reviewed the research progress of reversing ABC-mediated drug resistance by CRISPR/Cas9 system.

4.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
5.
Artigo em Inglês | MEDLINE | ID: mdl-33293998

RESUMO

Microctis Folium (MF), the dried leaves of Microcos paniculata, is widely used as a medical and food dual-purpose herb in South-east Asia and China. However, the quality control of MF is not well studied. A simple and reliable quality control method was urgently needed for its growing usage. Herein, at first, its main active components were identified by UPLC-ESI-qTOF-MS, and a representative MF flavone glycosides profile consisting of ten compounds was illustrated, which is the most detailed one up to now. Successively, using vitexin as the reference substance, a novel QAMS method with HPLC for quantification of the ten identified flavone glycosides was developed and methodologically validated. Furthermore, making use of the abovementioned QAMS method, quantitative profiling of 21 batches of prepared MF slices collected from different hospital pharmacies were performed. As a result, the total contents of ten flavone glucosides and the content of specific compound showed obvious variations. Using the ten compounds' contents dataset, the 21 batches of samples were divided into two distinct clusters by HCA. In sum, our results indicated that it was of great importance to take quality control of prepared MF slices and we presented a robust and simple method for their quantitative determination, which should be beneficial for the quality control of MF and its derived products.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1105-1114, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798384

RESUMO

OBJECTIVE: To analyze risk factors that affect survival and relapse of AML patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate the therapy choices after AML relapse. METHODS: Clinical data of 180 AML patients achieved complete remission (CR) before HSCT from January 2009 to December 2018 treated in our center were analyzed retrospectively. Risk factors for survival and relapse after allo-HSCT were analyzed by COX regression. RESULTS: Among 180 AML patients, 134 survived (74.4%), 46 patients died (25.6%), and 40 patients relapsed (22.2%). The rate of overall survival (OS), event-free survival (EFS) and cumulative rate of relapse in 5-years was 74.3%、42.5% and 25.0%, respectively. High-risk, adverse cytogenetics, CR2 at HSCT and no cGvHD were independent risk factors that affect OS. CR2 at HSCT, high-risk were independent risk factors that affect EFS. High-risk, MRD+ after one course of induction therapy, adverse cytogenetics and no cGVHD were independent risk factors that affect relapse. The OS rate of relapse patients could be improved by the usage of hypomethylation agents combined with G-CSF mobilized donor lymphocyte infusion (DLI), and 2-year OS rate was 62.5%. CONCLUSION: The survival rate of AML is greatly improved by allo-HSCT, but relapse is still one of the most important factors that influence survival of the AML patients. The maintenance therapy of hypomethylation agents combined with DLI may be a new effective treatment option for patients who relapse after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia , Indução de Remissão , Estudos Retrospectivos
7.
Front Microbiol ; 11: 375, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210947

RESUMO

Human noroviruses (NVs) are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of outbreaks are caused by genogroup II.4 (GII.4), with new variants emerging every 2 to 4 years. Immunocompromised patients are hypothesized to be important reservoirs where new NV variants emerge. Here, we examined intra-host NV variants and assessed immune-driven NV evolution in chronically infected immunocompromised hosts. Three NV GII.4-positive samples were collected from the same patient in different clinical phases following allogeneic hematopoietic stem cell transplantation, and had viral RNA concentrations of 2.46 × 106, 1.47 × 106, and 2.26 × 106 genome copies/mL. The non-synonymous (dN) and synonymous (dS) substitution ratio of the sequences in the partial P domain were >1, indicating strong positive selection in the patient. Both the number and the frequency of the single nucleotide variants increased over time in the patient. Also, the majority of capsid amino acid changes were located at blocking epitopes and histo-blood group antigen (HBGA)-binding sites, and 11 positive selection sites were found in the capsid region, of which 8 sites were presented in blocking epitopes or HBGA-binding sites. Homodimeric P-domain capsid models also suggested a structural change in the epitopes and HBGA-binding sites. The results suggested that novel variants of NV GII.4 with HBGA and antigenic site changes were produced in the immunocompromised patient. Further functional and epidemiological studies are needed to determine whether the new variants are a risk to public health.

8.
Food Funct ; 11(3): 2368-2379, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32129351

RESUMO

Among different types, Chinese propolis (ChPs) and Brazilian green propolis (BrGPs) have been shown to contain multi-functional properties. Despite extensive research in the field, reports comparing propolis from different geographical areas are still limited, compromising our current understanding of the potential therapeutic effect associated with propolis and its derived compounds. Herein, a comparative study between ChPs and BrGPs including their metabolite profile and bioactivities was performed. Interestingly, even when ChPs and BrGPs showed similar anti-inflammatory potential, our results showed that they contained very different levels of ethanol extract, total flavonoids and total phenolic acids and in fact, LC-MS metabolic profiling and pattern recognition could effectively distinguish ChPs and BrGPs. Moreover, all the propolis samples tested showed good anti-oxidant activity and no significant difference of free radical scavenging capacity existed between ChPs and BrGPs. In conclusion, ChPs and BrGPs have a distinct chemome, but their antioxidant and anti-inflammatory activities are similar.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 18-23, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027247

RESUMO

OBJECTIVE: To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Clinical data of 19 newly diagnosed as Ph+ ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed. RESULTS: There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively. CONCLUSION: First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of Ph+ALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.


Assuntos
Dasatinibe/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Feminino , Humanos , Masculino , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases , Estudos Retrospectivos , Resultado do Tratamento
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 248-254, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027285

RESUMO

OBJECTIVE: To investigate the therapeutic efficacy of using decitabine as maintenance therapy for patients with relapsed MDS/AML and as prophylactic therapy for patients with high-risk AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Clinical data of 10 patients with MDS/AML from November 2016 to May 2018 were analyzed retrospectively. Among 10 patients there were 4 cases of AML, 2 cases of MDS, and 4 cases of AML transformed from MDS (t-AML). The 10 patients were devided into 2 groups: the relapsed group (n=8) and the prophylactic group (n=2). In relapsed group the decitabine was used as maintenance therapy after achieved complete remission (CR) with decitabine chemotherapy. In prophylactic group the decitabine was used as prophylactic therapy if the patients didn't appear the symptom of graft-versus- host-disease (GVHD) during 30 to 45 d after allo-HSCT. Eight patients received G-CSF-mobilized donor lymphocyte infusion (DLI). The dosage of decitabine for maintenance therapy and prophylactic therapy was 5 mg/m2 for 7 to 10 days every 4 to 6 weeks, as 1 cycle, amount to 3 to 7 cycles. The dosage was adjusted by the endurance of patients. RESULTS: Until Nov 30, 2018, 7 out of 10 patients survived. The average survival time was 15.5±1.9 months. 1-year OS rate was 64.0%. Six patients appeared aGVHD, and four patients appeared cGVHD. CONCLUSION: The usage of decitabine combined with DLI in patients with relapsed MDS/AML and high-risk AML after allo-HSCT can prolong lives of patients, reduce relapsed rate, and provide the probability for long time survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Decitabina , Doença Enxerto-Hospedeiro , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos
11.
Sci Total Environ ; 708: 135011, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31806300

RESUMO

There is an increasing demand for urban form optimization to mitigate urban heat island (UHI) effect under the background of global climate change and urbanization. However, there is still a lack of understanding about how the relationship between urban form and UHI intensity changes under diverse urbanization contexts. This study aims to show the change patterns of the relationship between urban form and UHI intensity along the urban development gradient based upon the investigation of a total of 150 urban areas in the Jing-Jin-Ji region in China in 2000, 2005, 2010 and 2015. We defined a comprehensive urban development index taking into account the size of urban area, population density and night light intensity to classify the different levels of urban development. A multi-model comparison was carried out to validate the results. We found that the increase in urban continuity, sprawling, scale and density all enhanced UHI effect at the regional scale. However, the relationship between urban form indicators and UHI intensity demonstrated two opposite patterns along the urban development gradient: population density, geometric complexity and continuity, and general vegetation index of a city were found to be increasingly influential, while night light intensity, geometric elongation and forest coverage presented declining influence. Finally, the study obtained an ascending contribution rate curve for urban geometry indicators, a convex curve for urban size indicators and a declining curve for urban vegetation. These changes along the urban development gradient may be closely related to the changes of the microclimate in cities due to land use, social and economic activities in different urban development stages. The findings can contribute to more appropriate and effective urban planning in countries and regions undergoing rapid urbanization as a valuable reference.

12.
Cancer Manag Res ; 11: 10195-10203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824191

RESUMO

Purpose: To evaluate the role of Decitabine in the allo-HSCT conditioning regimen for intermediate- and high-risk patients with MDS or AML. Patients and methods: Retrospective analysis of data pertaining to 76 intermediate- and high-risk patients with MDS or AML who underwent allo-HSCT between December 2005 and June 2018 at the Peking University First Hospital. Forty patients received Decitabine-containing conditioning regimen before transplantation, while thirty-six patients received regimen without Decitabine. Results: Over a median follow-up of 40 months (range, 1 to 155), the cumulative incidence of grade II to IV acute graft versus host disease was 12.4% [95% confidence interval (CI) 4.9-30.9%] in the Decitabine group and 41.5% (95% CI 28.1-61.2%) in the non-Decitabine group (P=0.005). On multivariate analysis, Decitabine-containing conditioning regimen was found to protect against grade II to IV aGVHD (HR=0.279, 95% CI 0.102-0.765, P=0.013). Incidence of respiratory infection in the Decitabine and non-Decitabine groups was 22.5% and 52.78%, respectively (P=0.012). No significant between-group difference was observed with respect to 3-year OS, DFS, or RR (P=0.980, 0.959, and 0.573, respectively), while the median relapse time was longer in the Decitabine group [7 months (range, 2-12) versus 3 months (range, 2-4), P=0.171]. Decitabine-containing conditioning showed a tendency for lower relapse rate among higher risk patients, as assessed by IPSS R; however, the between-group difference was not statistically significant (P=0.085). Conclusion: Inclusion of Decitabine in the conditioning regimen for allo-HSCT in intermediate- and high-risk patients may lower the incidence of aGVHD and respiratory infections, and contribute to longer median relapse time.

13.
Life Sci ; 238: 116938, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593704

RESUMO

AIMS: To investigate the effect of 7-O-geranylquercetin (GQ), a derivative of quercetin (Q), on reversing drug resistance in breast cancer MCF-7/ADR cells and reveal the mechanisms related to P-glycoprotein (P-gp). MAIN METHODS: Cell viability was determined by MTT assay. Accumulation of adriamycin (ADR) in cells was determined by confocal fluorescence microscope and microplate reader while that of rhodamine (Rh) was measured by flow cytometry. Expression levels of P-gp and MDR1 gene in cells were detected by western blot and Real-Time PCR, respectively. Molecular docking of GQ and Q with P-gp was conducted using AutoDock program. Xenograft model was established by inoculating MCF-7/ADR cells in BALB/c-nude mice. Tumor bearing mice were administered with ADR via tail vein injection and/or GQ (Q) by gavage. Expression levels of P-gp in tissues were detected by western blot and immunohistochemistry. KEY FINDINGS: GQ could reverse drug resistance of MCF-7/ADR cells to ADR. GQ inhibited the efflux of ADR by down-regulating the expression of P-gp protein and its encoding gene MDR1 in MCF-7/ADR cells. Molecular modeling showed that GQ matched with P-gp better than Q. GQ enhanced the antitumor effects of ADR and decreased the expression of P-gp in mice and its activities were higher than that of Q. GQ could reverse drug resistance of MCF-7/ADR cells by down-regulating the expression of P-gp in vitro and in vivo. SIGNIFICANCES: The reversal effect of GQ on P-gp-mediated drug resistance indicates its potential as a reversal agent for drug resistance in cancer chemotherapy.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Quercetina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Quercetina/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1305-1310, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418397

RESUMO

OBJECTIVE: To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD). METHODS: The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively. RESULTS: Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P<0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1ß and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P<0.01), IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P<0.05), no significant difference of the rest cytokines was found between iMCD and the control group. CONCLUSION: IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.


Assuntos
Hiperplasia do Linfonodo Gigante , Citocinas , Humanos , Interleucina-12 , Interleucina-1beta , Plasma
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 796-801, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204934

RESUMO

OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION: Bone lymphoma is usually concealed onset,an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.


Assuntos
Neoplasias Ósseas , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos
16.
Int J Ophthalmol ; 12(6): 936-942, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236349

RESUMO

AIM: To investigate the occurrence of chronic photodamage in the cone-based retina, following long-term exposure to a 650-nm semiconductor laser (power: 2 mW). METHODS: Chickens fed for 1mo under natural light after hatching were irradiated with 650-nm laser light at different times each day. Fifteen animals were included in each group. Group A was a control group, irradiated with natural light during the entire study. Group B was irradiated with laser for 3 min/d. Group C was irradiated with laser for 6 min/d. Group D was irradiated with laser for 30 min/d. The duration of the light experiment was 6mo. We obtained data at 1, 3, and 6mo, including measuring the retinal thickness in vivo using optical coherence tomography, hematoxylin and eosin staining, TUNEL assay, apoptosis staining, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and Western blotting to detect changes in L/M opsins and rhodopsin. RESULTS: At 1mo, the MDA content in Group D was higher than that observed in Group A (P=0.019). At 3mo the MDA content in Groups C and D was higher than that reported in Group A (P=0.026, 0.003). At 6mo, the MDA content in Groups B, C, and D was higher than that observed in Group A (P=0.038, 0.032, 0.000, respectively). There was no difference in SOD activity, and L/M opsin and rhodopsin content between the groups at 1 and 3mo. The SOD activity in group D was significantly decreased at 6mo (P=0.000), as was the content of rhodopsin. There was no significant reduction observed in retinal thickness, abnormal cell arrangement, and positive staining of TUNEL in the groups during the 6-month study period. CONCLUSION: Irradiation using a 650 nm semiconductor laser (power: 2 mW) for 6min per day over 6mo do not cause photodamage. Similarly, a 3-month exposure of 30min per day do not cause damage. However, irradiation for 6mo resulted in a significant increase in the content of free radicals and a decrease in the content of rhodopsin in the retina, suggesting the presence of photodamage.

17.
Life Sci ; 227: 145-152, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31009625

RESUMO

AIMS: To investigate the antitumor effect of 7-O-geranylquercetin (GQ) combining with survivin siRNA (siSuvi) or IL-10 siRNA (siIL-10) to breast cancer. MAIN METHODS: Xenograft tumor model was established by subcutaneously inoculating human breast cancer MCF-7 cells in BALB/c nude mice. Transfection efficiency of siRNA mediated by cationic liposome CDO14 in MCF-7 cells and tumor bearing mice was measured by flow cytometer and living imaging sysytem, respectively. Cell viability was detected using CCK-8 assay. Cell apoptosis was determined by Hoechst33342 staining and AV-PI staining. Tumors bearing mice were administered with GQ by gavage, and/or with liposome CDO14 mediated siRNAs via tail intravenous injection. Expression levels of proteins and cytokines were detected by western blot and ELISA, respectively. KEY FINDINGS: Liposome CDO14 could deliver siRNA to tumor effectively. Combination of GQ and siSuvi promoted the antiproliferation and pro-apoptosis effects of GQ or siSuvi to MCF-7 cells, and reduced the level of survivin and raised the level of caspase-7 in cells. GQ combining with siSuvi inhibited the growth of tumor, down-regulated the expression of survivin and up-regulated the expression of caspase-7 in tumor tissue. Similarly, GQ combining with siIL-10 inhibited the growth of tumor, decreased the level of IL-10 and increased the level of TNF-α. These results revealed that GQ enhanced the pro-apoptosis effect of siSuvi on tumor cells and the modulating effect of siIL-10 on tumor microenvironment. SIGNIFICANCES: Synergistic anti-tumor effect of GQ and siRNAs against breast cancer proved that chemical drugs combining with siRNAs is a promising antitumor strategy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quercetina/análogos & derivados , Survivina/genética , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Lipossomos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Quercetina/metabolismo , Quercetina/farmacologia , RNA Interferente Pequeno/farmacologia , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
18.
BMJ Open ; 9(12): e033888, 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31892665

RESUMO

INTRODUCTION: For sciatica caused by lumbar disc herniation (LDH), the standard surgical technique is conventional microdiscectomy. In recent years, minimally invasive techniques (eg, percutaneous transforaminal endoscopic discectomy (PTED), paraspinal minitubular microdiscectomy (PMTM)) have gained increasing interest. PTED and PMTM are considered alternative minimally invasive techniques for the treatment of LDH. Due to insufficient evidence, the differences in efficacy between PTED and PMTM have been debated. A pragmatic, multicentre, non-inferiority, randomised controlled trial has been designed to determine the efficacy and cost-effectiveness of PTED versus PMTM for the treatment of LDH. METHODS AND ANALYSIS: A total of 280 patients (18-70 years) presenting with significant symptoms of sciatica and failure after 3 months of conservative treatment will be recruited. Patients must have an indication for surgery based on MRI demonstrating LDH with nerve root compression. Patients will be randomised to PTED or PMTM treatment. The primary outcome is Oswestry Disability Index scores. Secondary outcomes include Visual Analogue Scale scores, Short Form 36 health survey scores, physical examination, length of hospital stay, costs and complications. Outcomes will be measured the day following surgery, at 1 week, and at 1, 3, 6, 12 and 24 months after surgical treatment. Physical examination will be conducted at 1 week, 1 month and 12 months after surgery. The non-inferiority margin for the primary outcome is 5. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China (2018YF010-02). Results of the research will be published in an international peer-reviewed scientific journal and disseminated through presentation at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR1800015727; Pre-results.

19.
J Thorac Dis ; 10(5): 2648-2655, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29997926

RESUMO

Background: Esophageal cancer is one of the most prevalent malignancies with a high incidence and mortality in China, the main treatment for esophageal cancer at present is still surgery-based multimodality treatment, and surgery is still the most effective measure. However, the modes of surgical treatment for esophageal cancer have been diverse. The surgical approaches can be mainly divided into the left thoracic approach and right thoracic approach in China. The long-term survival of the patients treated through right approach was reported better than that through left thoracic approach, but until now no statistically significant difference was found between two approaches, especially, for those with middle and lower thoracic esophageal cancer without suspected upper mediastinal lymph node metastasis in preoperative examinations, no definite conclusion have been made on selection of the approach, therefore, this studies try to compare the long-term survival between two approaches . Methods: The data of 402 cases with complete resection and two-field lymph node dissection from January, 2011 to December, 2011 in the Cancer Hospital, Chinese Academy of Medical Sciences was retrospectively reviewed and analyzed. Propensity score matching (PSM) analysis and life-table in SPSS 22.0 and Stata 14.0 were used to analyze the survival. Results: Totally, 402 cases were surgically treated either via left or right thoracic approach. The overall 5-year survival rate of this series was 38%, it was 37% in 281 cases surgically treated through left approach, and 39% in 121 cases through right approach (P=0.908). The 5-year survival of 256 patients without suspected lymph node metastasis in the upper mediastinum based on the preoperative examinations surgically treated through left approach was 38% versus 43% of 88 cases through right approach (P=0.404). After PSM, the 5-year survival of 110 cases surgically treated through left approach was 32% versus 40% of another matched 110 cases through right approach (P=0.146). for the patients without suspected lymph node metastasis in the upper mediastinum based on preoperative examinations, the 5-year survival of 88 surgically treated through left approach was 33% versus 44% of another matched 88 cases through right approach (P=0.239). Conclusions: For the middle and lower thoracic esophageal cancer patients, whether or not who has suspected lymph node metastasis in the upper mediastinum based on preoperative CT and EUS, the surgical treatment through right thoracic approach can achieve better but not significantly better overall survival than that through left thoracic approach. Further prospective randomized clinical trials are still needed to verify this disputed issue on approach selection.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 765-771, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950217

RESUMO

OBJECTIVE: To analyze the incidence of bone marrow involvement in patients with different pathological types of lymphoma. METHODS: The results of bone marrow tests including bone marrow aspiration(BMA), flow cytometry detection, bone marrow biopsy(BMB) and 18F-FDG PET/CT, were analyzed retrospectively in 702 cases of newly diagnosed lymphoma with bone marrow assessment in our hospital from October 2000 to September 2016. If one of the above-mentioned 4 tests showed positive, the lymphoma patient was judged as bone marrow involved. RESULTS: The incidence of bone marrow involvement (BMI ) in the patients with NHL was much higher than that in patients with HL [32.6 %(201/616) vs 15%(13/86)](P<0.05). For patients with NHL, the incidence of bone marrow involvement in B-cell lymphoma was higher than that in T-cell lymphoma (37.0% vs 22.6%)(P<0.05). According to different pathological types, the incidences of BMI in the patient with mantle cell lymphoma, hepatosplenic T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL) and follical lymphoma (FL) were 88% (25/22), 100% (5/5), 21.8% (56/257), and 38.5% (15/39) , respectively. CONCLUSION: The incidence of bone marrow involvement varies in different pathological types of lymphoma.Bone marrow assessment has significant importance for stading of newly diagnosed lymphoma patients.


Assuntos
Medula Óssea , Biópsia , Fluordesoxiglucose F18 , Humanos , Incidência , Linfoma , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos
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