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1.
Entropy (Basel) ; 23(11)2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34828151

RESUMEN

Users of social networks have a variety of social statuses and roles. For example, the users of Weibo include celebrities, government officials, and social organizations. At the same time, these users may be senior managers, middle managers, or workers in companies. Previous studies on this topic have mainly focused on using the categorical, textual and topological data of a social network to predict users' social statuses and roles. However, this cannot fully reflect the overall characteristics of users' social statuses and roles in a social network. In this paper, we consider what social network structures reflect users' social statuses and roles since social networks are designed to connect people. Taking an Enron email dataset as an example, we analyzed a preprocessing mechanism used for social network datasets that can extract users' dynamic behavior features. We further designed a novel social network representation learning algorithm in order to infer users' social statuses and roles in social networks through the use of an attention and gate mechanism on users' neighbors. The extensive experimental results gained from four publicly available datasets indicate that our solution achieves an average accuracy improvement of 2% compared with GraphSAGE-Mean, which is the best applicable inductive representation learning method.

2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(3): 423-429, 2021 May.
Artículo en Zh | MEDLINE | ID: mdl-34018360

RESUMEN

OBJECTIVE: To investigate the differences in the osteogenic capacity of osteoporotic adipose-derived stem cells (OP-ASCs) and normal control adipose-derived stem cells (Ctrl-ASCs), and to examine the expression levels of RNA methyltransferase like 14 (Mettl14) and the Notch signaling molecule 1 (Notch1). METHODS: The osteoporosis (OP) model of SD rats was established with ovariectomy (OVX). Micro-CT, HE staining and Masson staining were performed to identify the successful establishment of the OP model, OP-ASCs and Ctrl-ASCs were isolated and cultured adherently. Then, the three-way differentiation capacity of the adipose-derived stem cells (ASCs) was determined through alizarin red staining, alcian blue staining and oil red O staining and flow cytometry was conducted to examine the surface antigens CD29, CD44, CD90, CD31, CD34, and CD45. Alizarin red staining and comparison of the mRNA and protein expression of Run-related transcription factor 2 (Runx2) were done to explore the differences in osteogenic potential of OP-ASCs and Ctrl-ASCs. Real-time PCR and Western blot were performed to explore the expression differences of Mettl14 and Notch1 at mRNA and protein levels between OP-ASCs and Ctrl-ASCs. RESULTS: Micro-CT, HE and Masson staining results showed that the number of trabecular bone decreased and the spacing increased in the tibias of the osteoporosis group (OP group) compared with those of the control group (Ctrl group), indicating that the OP model was established successfully. Three-way differentiation and flow cytometry results confirmed the successful isolation and culture of ASCs. After osteogenic induction, alizarin red staining showed that OP-ASCs had fewer number and more scattered distribution of mineralized nodules than Ctrl-ASCs did. The expression of Runx2 in OP-ASCs was lower than that in Ctrl-ASCs ( P<0.05). Mettl14 as well as Notch1 showed lower expression in OP-ASCs than they did in Ctrl-ASCs ( P<0.05). CONCLUSION: The osteogenic capacity of OP-ASCs was lower compared with that of Ctrl-ASCs, Mettl14 expression of OP-ASCs was decreased compared with that of Ctrl-ASCs, and the Notch signaling pathway was inhibited in OP-ASCs. The study helps build the foundation for further investigation in the specific mechanisms of Mettl14 and Notch1 during osteogenic differentiation of OP-ASCs.


Asunto(s)
Osteogénesis , Células Madre , Adipocitos , Tejido Adiposo , Animales , Diferenciación Celular , Células Cultivadas , Femenino , Humanos , Metiltransferasas , Ratas , Ratas Sprague-Dawley , Receptor Notch1/genética
3.
Biomed Environ Sci ; 27(5): 391-5, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24827722

RESUMEN

The effect of sterilization methods on biological activity of fibronectin on the surface of biomaterials was elaborated in the present study. Sterile protein- modified biomaterials were fabricated by microfilter filtration and UV irradiation, respectively. UV irradiation altered the conformation of surface- adsorbed fibronectin and further affected the attachment, morphology and biological function of endothelial cells. However, microfilter filtration did not to change the normal conformation of fibronectin, or the proliferation and biological function of endothelial cells, indicating that microfilter filtration sterilization is the most suitable method for protein-substrate.


Asunto(s)
Fibronectinas/efectos de la radiación , Prótesis e Implantes/microbiología , Esterilización/métodos , Adhesión Celular/efectos de la radiación , Filtración , Rayos Ultravioleta
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 847-851, 2024 Jun.
Artículo en Zh | MEDLINE | ID: mdl-38926978

RESUMEN

OBJECTIVE: To analyze the clinical features and laboratory indicators in patients with solid malignant tumor-associated venous thromboembolism (Ta-VTE), and to study the risk factors for Ta-VTE. METHODS: The hospitalized patients with VTE in Guizhou Provincial People's Hospital from January to December 2020 were enrolled, and they were divided into Ta-VTE group and pure VTE group based on the presence or absence of solid malignant tumor. The differences in clinical data and laboratory indicators between the two groups were analyzed, and the indicators with significant differences were included in logistic regression model to analyze the risk factors of Ta-VTE. RESULTS: A total of 288 patients with VTE were included in this study, including 64 cases in Ta-VTE group and 224 cases in pure VTE group, respectively. There were significant differences in the following indexes between the two groups, including the hospitalization time (14.20±15.29 d vs 10.05±6.90 d, t=3.112, P =0.002), pain (35.94% vs 65.18%, χ2=17.554, P =0.000), recent surgery (75.00% vs 37.50%, χ2=28.196, P =0.000), D-dimer [2.8 (0.92, 7.55) µg/ml vs 5.69 (2.25, 13.91) µg/ml, Z=-2.710, P =0.007], PLR[198.59 (139.54, 312.16) vs 149.76 (114.08, 233.66), Z=-2.924, P =0.003] and TBIL[10.90 (7.63, 15.68) µmol/L vs 12.90 (9.33, 18.28) µmol/L, Z=-2.066, P =0.039]. There was no significant difference in the other indicators (P >0.05). The result of multivariate logistic regression analysis showed that elevated PLR (OR =1.003, 95%CI : 1.000-1.006, P =0.027), recent surgery (OR =4.312, 95%CI : 2.093-8.885, P =0.000) and prolonged hospitalization (OR =1.037, 95%CI : 1.002-1.074, P =0.038)were independent risk factors for Ta-VTE. However, pain (OR =0.274, 95%CI : 0.133-0.564, P =0.000) was a protective factor. CONCLUSION: Elevated PLR level, recent surgery and prolonged hospital stay are independent risk factors for Ta-VTE patients, and rational use of these indicators is helpful for the clinical diagnosis and treatment of Ta-VTE patients.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno , Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Neoplasias/complicaciones , Factores de Riesgo , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Modelos Logísticos , Femenino , Masculino
5.
Nat Med ; 12(2): 175-7, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16444267

RESUMEN

For the majority of Duchenne muscular dystrophy (DMD) mutations, antisense oligonucleotide (AON)-mediated exon skipping has the potential to restore a functional protein. Here we show that weekly intravenous injections of morpholino phosphorodiamidate (morpholino) AONs induce expression of functional levels of dystrophin in body-wide skeletal muscles of the dystrophic mdx mouse, with resulting improvement in muscle function. Although the level of dystrophin expression achieved varies considerably between muscles, antisense therapy may provide a realistic hope for the treatment of a majority of individuals with DMD.


Asunto(s)
Distrofina/genética , Distrofia Muscular Animal/terapia , Oligodesoxirribonucleótidos Antisentido/administración & dosificación , Animales , Secuencia de Bases , Esquema de Medicación , Distrofina/metabolismo , Regulación de la Expresión Génica , Terapia Genética , Humanos , Inyecciones Intravenosas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Músculo Esquelético , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/patología , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Oligodesoxirribonucleótidos Antisentido/genética
6.
Artículo en Inglés | MEDLINE | ID: mdl-35942368

RESUMEN

Objective: This study aimed to analyze the clinical efficacy of the intervention of thumbtack needles (applicable to subcutaneous embedding) combined with Chinese medicine ironing therapy on postoperation nausea and vomiting (PONV). Methods: 106 patients who scheduled elective surgery were enrolled and randomized into control group and experimental group, with 53 cases in each group. The control group received modern medication, while the experimental group was given thumbtack needles combined with Chinese medicine ironing therapy based on the control group. The PONV score, incidence rate, gastrointestinal hormone level, Functional Living Index-Emesis (FLIE), and General Comfort Questionnaire (GCQ) of the two groups were compared. Results: After treatment, the incidence of PONV and GCQ in the experimental group was observed to be remarkably lower than that in the control group (P < 0.05), while the levels of gastrointestinal hormones and the level in the FLIE of the experimental group were comparatively higher than those in the control group (P < 0.05). Conclusion: Thumbtack needles combined with Chinese medicine ironing therapy can be utilized to reduce the incidence of PONV, to improve the level of gastrointestinal hormones, and to improve the comfort and quality of patients' lives.

7.
Front Public Health ; 10: 979933, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36203656

RESUMEN

Background: Human papillomavirus-positive (HPV+) cervical cancers are highly heterogeneous in clinical and molecular characteristics. Thus, an investigation into their heterogeneous immunological profiles is meaningful in providing both biological and clinical insights into this disease. Methods: Based on the enrichment of 29 immune signatures, we discovered immune subtypes of HPV+ cervical cancers by hierarchical clustering. To explore whether this subtyping method is reproducible, we analyzed three bulk and one single cell transcriptomic datasets. We also compared clinical and molecular characteristics between the immune subtypes. Results: Clustering analysis identified two immune subtypes of HPV+ cervical cancers: Immunity-H and Immunity-L, consistent in the four datasets. In comparisons with Immunity-L, Immunity-H displayed stronger immunity, more stromal contents, lower tumor purity, proliferation potential, intratumor heterogeneity and stemness, higher tumor mutation burden, more neoantigens, lower levels of copy number alterations, lower DNA repair activity, as well as better overall survival prognosis. Certain genes, such as MUC17, PCLO, and GOLGB1, showed significantly higher mutation rates in Immunity-L than in Immunity-H. 16 proteins were significantly upregulated in Immunity-H vs. Immunity-L, including Caspase-7, PREX1, Lck, C-Raf, PI3K-p85, Syk, 14-3-3_epsilon, STAT5-α, GATA3, Src_pY416, NDRG1_pT346, Notch1, PDK1_pS241, Bim, NF-kB-p65_pS536, and p53. Pathway analysis identified numerous immune-related pathways more highly enriched in Immunity-H vs. Immunity-L, including cytokine-cytokine receptor interaction, natural killer cell-mediated cytotoxicity, antigen processing and presentation, T/B cell receptor signaling, chemokine signaling, supporting the stronger antitumor immunity in Immunity-H vs. Immunity-L. Conclusion: HPV+ cervical cancers are divided into two subgroups based on their immune signatures' enrichment. Both subgroups have markedly different tumor immunity, progression phenotypes, genomic features, and clinical outcomes. Our data offer novel perception in the tumor biology as well as clinical implications for HPV+ cervical cancer.


Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Caspasa 7 , Quimiocinas , Citocinas , Femenino , Humanos , FN-kappa B , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Fosfatidilinositol 3-Quinasas , Receptores de Antígenos de Linfocitos B , Receptores de Citocinas , Factor de Transcripción STAT5 , Proteína p53 Supresora de Tumor , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología
8.
Nat Med ; 9(8): 1009-14, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12847521

RESUMEN

As a target for gene therapy, Duchenne muscular dystrophy (DMD) presents many obstacles but also an unparalleled prospect for correction by alternative splicing. The majority of mutations in the dystrophin gene occur in the region encoding the spectrin-like central rod domain, which is largely dispensable. Thus, splicing around mutations can generate a shortened but in-frame transcript, permitting translation of a partially functional dystrophin protein. We have tested this idea in vivo in the mdx dystrophic mouse (carrying a mutation in exon 23 of the dystrophin gene) by combining a potent transfection protocol with a 2-O-methylated phosphorothioated antisense oligoribonucleotide (2OMeAO) designed to promote skipping of the mutated exon*. The treated mice show persistent production of dystrophin at normal levels in large numbers of muscle fibers and show functional improvement of the treated muscle. Repeated administration enhances dystrophin expression without eliciting immune responses. Our data establishes the realistic practicality of an approach that is applicable, in principle, to a majority of cases of severe dystrophinopathy.


Asunto(s)
Distrofina/genética , Exones , Terapia Genética/métodos , Distrofia Muscular Animal/terapia , Distrofia Muscular de Duchenne/terapia , Mutación , Animales , Regulación de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos mdx , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Distrofia Muscular Animal/genética , Distrofia Muscular de Duchenne/genética , Oligonucleótidos Antisentido/metabolismo , Empalme del ARN
9.
Cancer Manag Res ; 13: 173-180, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33469361

RESUMEN

PURPOSE: The advanced lung cancer inflammation index (ALI) is a useful tool to predict the clinical outcome in several malignancies. The ALI not only contains indices related to inflammation but also the body mass index (BMI), which was reported to correlate with the sarcopenic status. However, to date, its predictive significance in metastatic melanoma patients treated with second-line immunotherapy has not been evaluated. METHODS: We retrospectively analyzed data from patients who were diagnosed with metastatic melanoma and treated with immunotherapy as second-line therapy between 2016 and 2019. Weight, height, neutrophil, lymphocyte and serum albumin were collected at baseline prior to receiving immunotherapy. The BMI was calculated by dividing the weight by height squared. The neutrophil-to-lymphocyte ratio (NLR) was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The ALI was defined as follows: ALI=BMI×serum albumin/NLR. The receiver operator curve (ROC) was used to determine the best cutoff value for ALI in predicting disease control (consisting of complete response, partial response and stable disease). The aim of this study was to investigate whether the ALI is a predictive indicator for progression-free survival in melanoma patients. RESULTS: Forty-three patients were included in this retrospective cohort study. By ROC, ALI>50.98 before immunotherapy was predictive of disease control. Baseline continuous variables, such as BMI, NLR, C-reactive protein and C-reactive protein-to-albumin ratio, had significantly worse scores in patients of the low-ALI group (n=24) than high-ALI group (n=19). The median progression-free survival was significantly worse in the patients with ALI<50.98 than the patients with ALI>50.98 (2.60 months vs 11.17 months, P = 0.023, hazard ratio: 2.241, 95% confidence interval: 1.167-5.097). CONCLUSION: The advanced lung cancer inflammation index (ALI) >50.98 before immunotherapy is a strong predictor for disease control. The ALI also provides great predictive value for metastatic melanoma patients treated with immunotherapy as second-line therapy.

10.
Int J Biol Macromol ; 192: 1021-1028, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34666131

RESUMEN

Interleukin (IL)-11 is a multifunctional cytokine belonging to the IL-6 family, which plays essential roles in immune response. However, much less is known about the immunological functions of IL-11 in teleost. In this study, we investigated the immune properties of a teleost IL-11 homologue (CsIL-11) from tongue sole Cynoglossus semilaevis. CsIL-11 possesses four conserved α-helices and conserved CsIL-11 receptor binding residues L86 and R187, and shares 23.3%-80.1% identities with other IL-11 homologues. CsIL-11 expression was constitutive in tissues, with most abundant in blood and least abundant in spleen, and upregulated by bacterial challenge in blood, spleen, and head kidney. Recombinant CsIL-11 (rCsIL-11) in the native form of monomer, could bind to peripheral blood leukocytes (PBLs) membrane and enhance the activation and phagocytosis of PBLs. When administered in vivo, rCsIL-11 could markedly promote the host to defend against microbial infection. Overall, our findings show that CsIL-11 plays a pivotal role in regulating PBLs phagocytosis and antibacterial immunity.


Asunto(s)
Infecciones Bacterianas/veterinaria , Enfermedades de los Peces/etiología , Enfermedades de los Peces/metabolismo , Peces/fisiología , Interleucina-11/metabolismo , Fagocitosis/inmunología , Secuencia de Aminoácidos , Animales , Resistencia a la Enfermedad , Susceptibilidad a Enfermedades , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata , Interleucina-11/química , Interleucina-11/genética , Filogenia , Relación Estructura-Actividad
11.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(2): 170-176, 2020 Apr 01.
Artículo en Zh | MEDLINE | ID: mdl-32314891

RESUMEN

OBJECTIVE: To study the precision of digital guide plates applied to the implant surgery of anterior teeth. METHODS: Fifty patients scheduled to receive implant restoration treatment in anterior teeth were enrolled in this study and divided into two groups (n=25, each group): those who were given routine implant restoration treatment (control group, 45 implants) and those who received implant restoration treatment using a digital guide plate (test group, 51 implants). After implantation, planned and placed implants were superimposed using digital software, and deviations (corona, apex, depth, degree) were analyzed. Esthetic parameters were assessed at 1 week (baseline), 6 month, and 1 year post final restoration. Pink esthetic (PES) and white esthetic (WES) scores were respectively used to evaluate the soft tissue and restoration esthetic outcome. RESULTS: The deviation parameters in the test group were significantly lower than those in the control group (P<0.05). PES and WES values recorded for the control group at 1 week, 6 month, and 1 year post final restoration were significantly lower than those in the test group (P<0.05). CONCLUSIONS: The digital guide plate can improve the accuracy of the three-dimensional position of implants in the maxillary esthetic zone. As such, this device may play an important role in obtaining the ideal aesthetic effects of maxillary anterior teeth.


Asunto(s)
Implantes Dentales de Diente Único , Implantes Dentales , Coronas , Estética Dental , Humanos , Maxilar , Resultado del Tratamiento
12.
Mol Med Rep ; 22(5): 4079, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32901842

RESUMEN

Following the publication of this article, an interested reader drew to the Editor's attention that certain GAPDH control bands were strikingly similar, comparing between two different figures in the paper. Two GAPDH bands in Fig. 1D appeared to be duplicates of two GAPDH bands featured in Fig. 3B, although different conditions were represented by these figures. Furthermore, the protein bands featured in the two lanes in the left p62 panel in Fig. 1D, when flipped horizontally, looked remarkably similar to the Cyclin B lanes featured in the right-hand gel of Fig. 3B. Finally, the same protein bands were also strikingly similar to bands featured in Fig. 4B, albeit in a different experimental context. The Editor of Molecular Medicine Reports has investigated this matter, and we were able to confirm that the two sets of data bands featured in this trio of figures were indeed the same ones, beyond all reasonable doubt. Consequently, the Editor has decided that this article should be retracted from the publication on the basis of an overall lack of confidence in the presented data. The Editor apologizes to the readership of the Journal for any inconvenience caused. [the original article was published in Molecular Medicine Reports 11: 1214-1220, 2015; DOI: 10.3892/mmr.2014.2853].

13.
J Physiol ; 587(1): 155-63, 2009 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-19015190

RESUMEN

Each heartbeat is triggered by a pulse of intracellular calcium ions which bind to troponin on the actin-containing thin filaments of heart muscle cells, initiating a change in filament structure that allows myosin to bind and generate force. We investigated the molecular mechanism of calcium regulation in demembranated trabeculae from rat ventricle using polarized fluorescence from probes on troponin C (TnC). Native TnC was replaced by double-cysteine mutants of human cardiac TnC with bifunctional rhodamine attached along either the C helix, adjacent to the regulatory Ca(2+)-binding site, or the E helix in the IT arm of the troponin complex. Changes in the orientation of both troponin helices had the same steep Ca(2+) dependence as active force production, with a Hill coefficient (n(H)) close to 3, consistent with a single co-operative transition controlled by Ca(2+) binding. Complete inhibition of active force by 25 microM blebbistatin had very little effect on the Ca(2+)-dependent structural changes and in particular did not significantly reduce the value of n(H). Binding of rigor myosin heads to thin filaments following MgATP depletion in the absence of Ca(2+) also changed the orientation of the C and E helices, and addition of Ca(2+) in rigor produced further changes characterized by increased Ca(2+) affinity but with n(H) close to 1. These results show that, although myosin binding can switch on thin filaments in rigor conditions, it does not contribute significantly under physiological conditions. The physiological mechanism of co-operative Ca(2+) regulation of cardiac contractility must therefore be intrinsic to the thin filaments.


Asunto(s)
Calcio/metabolismo , Miocardio/metabolismo , Troponina C/química , Animales , Colorantes Fluorescentes , Humanos , Técnicas In Vitro , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Contracción Miocárdica/fisiología , Miocitos Cardíacos/metabolismo , Miosinas/metabolismo , Estructura Secundaria de Proteína , Ratas , Ratas Wistar , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Troponina C/genética , Troponina C/metabolismo
14.
Zhonghua Zhong Liu Za Zhi ; 31(1): 75-8, 2009 Jan.
Artículo en Zh | MEDLINE | ID: mdl-19538878

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of the combination of oxaliplatin and ELF (VP16/CF/5-Fu) regimen in the treatment of patients with advanced gastric cancer. METHODS: Oxaliplatin was given at a dose of 100 mg/m(2) i.v. 2 hours D1, calcium folinate (CF) 200 mg/m(2) i.v. 1/2 hour D1 approximately D3, 5-fluorouracil (5-Fu) 500 mg/m(2) i.v. 2 hours D1 approximately D3 and etoposide 100 mg/m(2) i.v. 3 hours D1 approximately D3. Cycles were repeated every 21 days. Efficacy and safety were evaluated every 2 cycles. RESULTS: Sixty-nine patients were enrolled into the study. All cases were pathologically confirmed as gastric cancer (adenocarcinoma in 57 cases and signet ring cell carcinoma in 12 cases). 42 patients had newly diagnosed disease, and 27 patients had received previous chemotherapy. 62 patients were analyzed for response (7 complete responses and 25 partial responses) with total response rate 51.61%. The median time to progression was 5.7 months and the median overall survival was 9.2 months. The most common hematologic toxicities were anemia (29.0%), leucopenia (51.2%) and thrombocytopenia (21.2%). No grade 4 and grade 5 hematologic toxicities were observed. The most common non-hematologic toxicities were nausea (46.5%), vomiting (41.1%), peripheral sensory neuropathy (47.1%), and grade 2 alopecia (27.3%). CONCLUSION: This oxaliplatin combined with ELF regimen shows good efficacy and acceptable safety in advanced gastric cancer patients. It is worthy to be proved as a suitable alternative regimen in this indication.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células en Anillo de Sello/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Anemia/inducido químicamente , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células en Anillo de Sello/patología , Etopósido/efectos adversos , Etopósido/uso terapéutico , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Leucopenia/inducido químicamente , Levoleucovorina , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Estadificación de Neoplasias , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Inducción de Remisión , Neoplasias Gástricas/patología , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Vómitos/inducido químicamente
15.
Zhonghua Yi Xue Za Zhi ; 89(24): 1714-6, 2009 Jun 23.
Artículo en Zh | MEDLINE | ID: mdl-19957534

RESUMEN

OBJECTIVE: To screen new candidate molecular-targeted anti-leukemia compounds with potential functions of targeted up-regulating ID4 gene expression. METHODS: Promoter region of ID4 gene including the upstream - 3000 bp sequence of transcriptional start site and message RNA sequence were fished out. Online promoter analysis tools of TESS and Genomax were used to search possible sequence of transcriptional start site and message RNA sequence were fished out. Online promoter analysis tools of TESS and Genomax were used to search possible cis-acting structure from human transcription factor database. The activity of related drugs with potential effects upon ID4 gene expression was analyzed using SAGE database. GEO database was applied to search the gene expression profiling regulated by ID4 gene. Finally, similar analysis between gene expression profiling by ID4 and genome-wide profiling regulated by 163 known drugs or active compounds was manipulated to screen the drugs and candidate compounds with similar gene expression profiling with ID4 gene. MOLT4 cell line was treated with the above candidate active compounds to investigate the ID4 gene expression by RT-PCR assay. RESULTS: ID4 gene had a type II promoter with a typical TATA box in upstream -45 bp of transcription start site. The 1300 bp-length promoter of ID4 gene contained a few cis-acting structures classified into two function types, i. e. positive regulatory type, including transcription factors Spl and c-Myb, cAMP, glucocorticoid receptor (GR) and estrogen receptor (ER), and negative regulatory type, including Wilms tumor-1 (WT1) and early growth response-2 (EGR2). The similarity of gene expression profiling was identified between cAMP and ID4 gene. ID4 gene expression was induced in MOLT4 cell line after treatment with calcium dibutyryladenosine cyclophosphate at the concentration of 0.1 mmol/L. CONCLUSION: The comprehensive bioinformatic analysis, based upon the combination of regulatory sequence prediction of promoter, similarity analysis of gene expression profiling and literature review, can be considered as a practical tool in screening the candidate drugs with the activity of targeted regulating functional genes. Calcium dibutyryladenosine cyclophosphate can induce ID4 gene expression in leukemic cells.


Asunto(s)
Biología Computacional , Proteínas Inhibidoras de la Diferenciación/genética , Línea Celular Tumoral , Humanos , ARN Mensajero/genética , Secuencias Reguladoras de Ácidos Nucleicos , Análisis de Secuencia de ADN , Regulación hacia Arriba
16.
Transl Oncol ; 12(6): 828-835, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30981094

RESUMEN

BACKGROUND: Pembrolizumab shows robust antitumor activity and favorable safety in metastatic melanoma. KEYNOTE-151 evaluated pembrolizumab in Chinese patients, who have more aggressive melanoma subtypes than other populations. METHODS: Chinese patients aged ≥18years with advanced melanoma previously treated with one line of therapy received pembrolizumab 2 mg/kg every 3 weeks for 35 cycles or until confirmed disease progression, intolerable toxicity, or study withdrawal. Primary end points were objective response rate (ORR) per RECIST v1.1 by blinded independent central review and safety. Key secondary end points included duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 and overall survival (OS). RESULTS: Median age was 52 years (N=103); 37.9% had acral and 14.6% had mucosal melanoma. Median follow-up was 7.9months at data cutoff (December 27, 2017). ORR was 16.7% (95% CI, 10.0-25.3%) (1 complete, 16 partial responses). Disease control rate was 38.2%. ORR was 15.8% for acral, 13.3% for mucosal melanoma. Median DOR was 8.4months; 65.6% of patients had response duration ≥6months. Median PFS was 2.8months (95% CI, 2.7-3.5months); 6-month rate was 20.4%. Median OS was 12.1months (95% CI, 9.6months-not reached); 6-month rate, 75.7%; 12-month rate, 50.6%. Treatment-related AEs (TRAEs) occurred in 87 (84.5%) patients; 9 (8.7%) experienced grade 3/4 TRAE and 2 (1.9%) discontinued because of TRAE; none died. Two deaths occurred that were unrelated to treatment. CONCLUSIONS: Pembrolizumab was well tolerated and provided clinically meaningful antitumor activity as second-line therapy in Chinese patients with advanced melanoma.

17.
J Cancer ; 9(16): 2795-2801, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30123347

RESUMEN

Background: Multiple primary malignant tumors (MPMTs) are defined as two or more histologically distinct malignancies in one individual, standard treatments for MPMTs are not well established, we aimed to clinical analyze the factors influence the treatment efficacy of MPMTs. Methods: This study retrospectively analyzed 15,321 malignant tumor patients at the Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, China, between March 2006 and June 2016. The survival analysis was performed with SPSS version 22.0 (SPSS Inc., Chicago, IL, USA) with Kaplan-Meier methodology. Results: The prevalence of MPMTs in our study was 1.09% (167/15321), with a male to female ratio of 2.34:1. Specifically, 98 patients harbored synchronous MPMTs, and 69 patients harbored metachronous MPMTs. The most common cancer pairs were digestive-digestive tumor (43 patients, 25.75%), digestive-lung cancer (32 patients, 19.16%), and head & neck-digestive tumor (11 patients, 6.59%). Among patients with synchronous and metachronous first primary cancers, 65.86% received surgery. 33.33% (27/81) of the patients with synchronous MPMTs received simultaneous resection. Of the 69 patients with metachronous MPMTs, 31.88% (22/69) were treated with surgery alone, 62.32% (43/69) received chemotherapy and/or radiotherapy for the first primary tumor, and 44.93% (31/69) received surgery for the other primary tumor. 98.20% (164/167) of patients with MPMTs were effectively followed up, the overall 2- and 5-year survival rates were 54.3% and 31.4%, respectively, with a median survival time of 28.0 months. Conclusions: The early diagnosis of rare MPMTs should not be neglected in patients not only when treated for a primary malignancy but also during long-term follow-up. Effective treatment for MPMTs may yield promising curative effect and warrants further investigation.

18.
Chin Med Sci J ; 22(3): 187-91, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17966168

RESUMEN

OBJECTIVE: To investigate the methylation status of LRP15 gene in acute leukemia (AL) patients and its role in the tumorigenesis. METHODS: The methylation of LRP15 promoter and first exon of bone marrow mononuclear cells in 73 patients with AL, 10 with chronic leukemia (CL), 9 with hematological benign diseases, and 20 healthy transplantation donors was analyzed by using methylation specific polymerase chain reaction. The methylation of LRP15 gene promoter and first exon in COS7, K562, and HL60 cell lines was also assayed. RESULTS: No LRP15 gene promoter methylation was detected in COS7 cell line. LRP15 gene promoter was methylated in K562 and HL60 cell lines. No deletion of LRP15 gene was detected in all samples. In nearly all French-American-British leukemia subtypes, we found that frequency of LRP15 methylation in adult patients with AL was 71.23% (52/73). There was no detectable methylation in any of the 20 healthy donors and 8 chronic myeloid leukemia patients. The difference in frequency of LRP15 methylation between AL patients and healthy donors or CL patients (10.00%, 1/10) was significant (P < 0.01). Hypermethylation of LRP15 gene was found in 57.14% (16/28) of newly diagnosed AL patients, 83.33% of relapsed AL patients respectively, which was significantly different (P < 0.05). We also demonstrated LRP15 methylation in 55.56% (5/9) adults with benign hematological diseases. CONCLUSIONS: LRP15 methylation changes are common abnormalities in leukemia. LRP15 is postulated to be a tumor suppressor gene.


Asunto(s)
Metilación de ADN , Leucemia/genética , Proteínas de Neoplasias/genética , Enfermedad Aguda , Animales , Secuencia de Bases , Células COS , Línea Celular Tumoral , Chlorocebus aethiops , Cartilla de ADN , Humanos , Regiones Promotoras Genéticas
19.
Zhongguo Zhong Yao Za Zhi ; 32(14): 1416-8, 2007 Jul.
Artículo en Zh | MEDLINE | ID: mdl-17966354

RESUMEN

OBJECTIVE: To investigate the chemical constituents of Helwingia Chinensis. METHOD: Compounds were isolated with silica gel, Sephadex LH - 20 and polyamide chromatography, and their structures were elucidated by means of spectral analysis. RESULT: Six compounds were isolated and identified as cinnamic acid (1), gult-5-en-3beta-ol (2), friedelin (3), alpha-amyrin (4), luteolin-7-O-beta-D-glucoside (5) and 4, 5-dimethoxy-1, 2-benzoquinone (6). CONCLUSION: All these Compounds were obtained from H. chinensis for the first time.


Asunto(s)
Cinamatos/aislamiento & purificación , Cornaceae/química , Ácido Oleanólico/análogos & derivados , Plantas Medicinales/química , Triterpenos/aislamiento & purificación , Cinamatos/química , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Triterpenos/química
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