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The efficacy of HPV vaccine in preventing cervical cancer has been demonstrated in numerous clinical trials and clinical uses. The follow-up after clinical trials usually last for 5-6 years to evaluate the long-term efficacy, and a series of long-term follow-up studies have been conducted in some regions. The literature retrieval of HPV vaccine long term efficiency research both at home and abroad indicated that the protective efficacy of the vaccine against vaccine-type-related cervical intraepithelial neoplasia grade 2 and above is higher than 90%.
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Humanos , Papillomaviridae , Pesquisa Biomédica , Vacinas contra PapillomavirusRESUMO
Using the concepts and methods of epigenetics and metabolomics, to investigate the overall action molecular mechanism of Chrysanthemi indici C (CIC), the anti-hepatitis B virus (HBV) active extracts from Flos chrysanthemi indici. The inhibitory effects of CIC on proliferation and hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg) and HBV-DNA of HepG2.2.15 cells were detected by CCK-8 and antigen kit. The DNA methyltransferases (DNMTs)/ten-eleven-translocation-2 (TET2) equilibrium was detected by ELISA. Illumina 850K methylation chip, pyrosequencing and qPCR were used to determine the action pathway and target of CIC by GO and KEGG analysis. Cell metabolites were extracted with 80% methanol, and the changes of differential metabolites, differential metabolic pathways and cell microenvironment were detected by LC-MS and other metabolomics methods. The results showed that CIC could inhibit the proliferation, HBsAg, HBeAg and HBV-DNA of HepG2.2.15 cells obviously, down-regulate DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and DNA methyltransferase 3b (DNMT3b), up-regulate TET2, and restore the balance of DNMTs/TET2. The action targets of CIC were phospholipase C gamma 2 (PLCG2), phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 5-hydroxytryptamine receptor 2B (HTR2B), nerve growth factor (NGF), mainly involved in lipid metabolism, inflammation mediated regulation of transient receptor potential (TRP), phospholipase D signaling and advanced glycation end product-receptor for AGE (AGE-RAGE) signaling in diabetic complications pathways. CIC could significantly affect fatty acid metabolism and had great influence on phenolic acid, alkaloid and lipid metabolites in cell microenvironment. These results suggest that the action mechanism of CIC may be the synergistic action of multiple pathways and multiple targets, including related inflammatory pathways, immune pathways and lipid metabolism, through regulating epigenetic expression balance and restoring the balance of cell microenvironment.
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OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração por Inalação , China , Infecções por Coronavirus , Diagnóstico , Tratamento Farmacológico , Mortalidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Medicamentos de Ervas Chinesas , Seguimentos , Medicina Integrativa , Interferon-alfa , Lopinavir , Pandemias , Pneumonia Viral , Diagnóstico , Tratamento Farmacológico , Mortalidade , Medição de Risco , Síndrome Respiratória Aguda Grave , Diagnóstico , Tratamento Farmacológico , Mortalidade , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Traditional Chinese medicine has multi-component, multi-target, and multi-path action characteristics and complexity, which makes the task of modernizing traditional Chinese medicine arduous, and many medical researchers have made unremitting efforts to this end. The development of systems biology and omics has ushered in an opportunity for the integration of traditional Chinese medicine and modern science. In particular, the characteristics integrity, dynamics, personalization, and interaction with the environment of epigenetics and metabolomics are consistent with function concept of traditional Chinese medicine. The application of popular DNA methylation, histone modifications, miRNA regulation of epigenetic research, and the application of metabolomics in the substance basis, quality control, pharmacodynamic action mechanism in traditional Chinese medicine research are reviewed in this paper. This paper also puts forward the idea that combining the two and innovative application can clarify the scientific connotation of the whole action mechanism of traditional Chinese medicine and the mechanism of multi-component, multi-channel, and multi-target synergistic action at the micro level, and explore a new research model for the scientific connotation of the core thought of traditional Chinese medicine.
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OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração por Inalação , China , Infecções por Coronavirus , Diagnóstico , Tratamento Farmacológico , Mortalidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Medicamentos de Ervas Chinesas , Seguimentos , Medicina Integrativa , Interferon-alfa , Lopinavir , Pandemias , Pneumonia Viral , Diagnóstico , Tratamento Farmacológico , Mortalidade , Medição de Risco , Síndrome Respiratória Aguda Grave , Diagnóstico , Tratamento Farmacológico , Mortalidade , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Apatinib is a kind of antiangiogenesis drug of small molecular tyrosine kinase inhibitor, which can strongly against tumor angiogenesis by inhibiting vascular endothelial growth factor receptor 2 with highly selectivity. Apatinib can block cell cycle and reverse drug resistance. Clinical studies have shown that Apatinib is effective for many malignant tumors,including non-small cell lung cancer,breast cancer and gastric cancer,which has encouraging objective response rate and survival benefit. Apatinib also has good safety and tolerance.
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To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network. The results showed that a total of 1 570 lncRNAs, 54 miRNAs, and 17 mRNAs were differentially expressed in CCRCC, and most of their expression levels were up-regulated (false discovery rate 2). The ceRNA regulatory network showed the interaction between 89 differentially expressed lncRNAs and 9 differentially expressed miRNAs. Further survival analysis revealed that 38 lncRNAs (including COL18A1-AS1, TCL6, LINC00475, UCA1, WT1-AS, HOTTIP, PVT1, etc.) and 2 miRNAs (including miR-21 and miR-155) were correlated with the overall survival time of CCRCC ( < 0.05). Together, this study provided us several new evidences for the targeted therapy and prognosis assessment of CCRCC.
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Humanos , Carcinoma de Células Renais , Genética , Neoplasias Renais , Genética , MicroRNAs , Genética , RNA Longo não Codificante , Genética , TranscriptomaRESUMO
Aim To investigate the inhibitory effect of polyphenol from Cortex Mori( CMP) on melanogenesis in mouse melanoma B16 cells and its possible mecha- nism. Methods Melanoma B16 cells with high ex-pression melanin were induced by α-melanocyte-stimu-lating hormone ( α-MSH) to establish cell model. Cell viability was detected by MTT assay. The melanin syn-thesis and tyrosinase activity were measured by NaOH and L-Dopa assays, respectively. The tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), tyrosi-nase-related protein-2 ( TRP-2 ) and microphthalmia associated transcription factor ( MITF ) protein and mRNA levels were measured by Western blot and qRT-PCR, respectively. Results CMP could inhibit the melanin synthesis and tyrosinase activity in α-MSH stimulated B16 cells in a dose-dependent manner ( P<0.05) . The melanin content and tyrosinase activity significantly decreased by 52.95% , 32.85% at 20 mg ·L-1of CMP, respectively. Treatment of 100 mg· L-1of arbutin reduced the melanin content and tyrosi- nase activity by 17.29% , 16.75% , respectively. Based on the results of this study, CMP showed a stronger anti-melanogenesis activity than that of positive control arbutin. After treated by CMP, the protein and mRNA levels of TYR, TRP-1, TRP-2 and MITF were significantly inhibited compared to the α-MSH group ( P<0.05) . Conclusions CMP could suppress the melanogenesis in α-MSH stimulated B16 cells, and its mechanism may be related to its regulation of the pro-tein and mRNA expressions of TYR, TRP-1, TRP-2 and MITF, and the inhibition of tyrosinase activity.
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The aim of this article is to study the regulatory feedback loop between β-catenin and IQ motif containing GTPase activating protein 1 (IQGAP1), as well as the effect of this regulation loop in colon cancer cell proliferation. Western blot was used to detect the expression of IQGAP1 and β-catenin after changing their expression respectively by transfection in SW1116 cells. CCK-8 cell proliferation assay was used to detect the effect of IQGAP1 involved in the proliferation of SW1116 cells promoted by β-catenin. The results of Western blot indicated that β-catenin could positively regulate IQGAP1, while IQGAP1 silencing could up-regulate β-catenin, forming a negative feedback loop. The results of CCK-8 showed that IQGAP1 silencing inhibited β-catenin-mediated proliferation in SW1116 cells. In conclusion, our research reveals a negative regulatory feedback loop between β-catenin and IQGAP1 which has a remarkable effect on the proliferation ability of colon cancer cells.
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Ginseng is a traditional medicine in Asian countries. Ginsenoside has the main active ingredient, exhibit cardiovascular, tumor, and central nervous system activities. In particular, protopanaxatriol-type ginsenosides Rh1, exhibits anti-inflammatory, anti-allergic, and memory improvement activities. Ginsenoside Rh1 is only found in trace amounts in Panax ginseng, Panax pseudoginseng var. notoginseng, and Panax quinquefolius. Biotransformation of rare ginsenosides has become an effective way. In this paper, the research progress of transformation of ginsenoside saponins by biotransformation to produce rare ginsenoside Rh1 is reviewed, which provides a useful reference for the further development and preparation of ginsenoside Rh1.
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Objective The guanine exchange factors( GEFs) of Dbl family is a major regulatory unit for the malignant transformation of Rho family proteins. It plays a role by converting Rho protein from inactive GDP form to GTP form of Rho protein. In this paper,we discuss the structure and function of a GEF molecule-ARH-GEF 10,and discuss its role in the process of tumor development. Methods The expression of ARHGEF 10 in 42 normal tissues was measured by Real-Time PCR. GST-pulldown technique was used to detect the GEF ac-tivity of ARHGEF 10 in vivo. The transcription factor activity of downstream small molecules was detected by dual-luciferase report gene assay. The high expressive effect of ARHGEF 10 on normal cytoskeleton morphology was performed by dual immunofluorescence staining labeling method. High expressive effects of ARHGEF 10 on cell proliferation,invasion and tumorigenic ability in vitro were examined using CCK8,Transwell and soft agar clony formation assays. Results ARHGEF 10 has a typical GEFs structure,which binds to RhoA in vitro and promotes the proliferation and invasion of NIH3T3 cells,and has significant ability to clone in vitro. Conclusion ARH-GEF 10 is a typical family molecule of guanosine exchange factor that activates RhoA of Rho family,which has obvious oncogene characteristics.
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Objective:The significant role of long non-coding RNAs (lncRNAs) in early diagnosis and predicting prognosis has been recognized in various cancers recently.However,the prognostic value of HOXA transcript at the distal tip (HOTTIP),a vital lncRNA in tumorigenesis,remains unclear.In this study,we evaluated its prognostic value by analyzing the correlation of HOTTIP expression with overall survival (OS),lymph node metastasis (LNM) and distant metastasis (DM) in different cancer types by meta-analysis.Methods:We performed a systematic search in PUBMED,MEDLINE,Web of Science and Cochrane Library update to November of 2016.A total of 604 patients from 6 studies were included in final analysis and went through a quantitative meta-analysis by Review manager 5.3.Results:We demonstrated that high expression of HOTTIP had a significant correlation with poor OS (hazard ratio [HR] =2.37,95% confidence interval [CI] =1.81-3.10,p<0.001),high LNM rate (odds ratio [OR]=2.29,95%CI=1.54-3.40,p<0.001) as well as more DM occurrence (OR=3.30,95%CI=1.78-6.12,p<0.001).Conclusion:Our results indicated that long non-coding RNA HOTTIP may serve as a potential prognostic biomarker in cancer progression.
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Objective To investigate the clinical application and manifestation of dynamic contrastenhanced MRI (DCE-MRI) in differentiating true progession from pseudoprogression in patients with gliobastomas.Methods Twenty five glioma patients were treated with postoperative concurrent chemoradiotherapy and enrolled in this study.All patients were underwent DCE-MRI using a 1.5T scanner.Fifteen patients were confimmed by secondary pathology or clinical and imaging follow-up of patients with gliomas true progession (TP),10 patients were pseudoprogress (PP).Nonparametric Mann-Whitney test was used to compare perfusion parameters between two groups (TP and PP),were used for receiver operating characteristic (ROC) curve analysis to clear if these parameters can be the indicators to differentiate true progession from pseudoprogression.Results Ktrans (volume transfer constant),Ve (fractional volume of extravascular extracellular) values between TP and PP glioma groups were statistically significant,K and Ve values were significantly higher in the TP group than in the PP group (P < 0.05).The areas under the ROC curve are 0.990 and 0.847,respectively.Kep (efflux rate constant) value,Vp (fractional volume of plasma) value in the identification of glioma TP group and PP group was not statistically significant (P > 0.05).Conclusions DCE-MRI can be used to identify glioma TP and PP,Ktrans value and Ve value have clinical significance.
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The multumodal molecular umagung technology untegrates the advantages of varuant umagung methods whuch can provude a more comprehensuve and accurate unformatuon un cancer duagnosus, and realuze tumely personaluzed duagnosus of tumor at molecular and cellular level, quantutatuvely dynamuc monutorung of tumor, etc. Thus revuew untroduces the basuc concepts of multumodal molecular umagung, umplementatuon methods and recent research progress of the applucatuons un tumor duagnosus. The development trend of multumodal molecular umagung un tumor duagnosus us also prospected.
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Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i. e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.
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Humanos , Linhagem Celular Tumoral , Neoplasias do Colo , Diagnóstico , Compostos Férricos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita , Química , Imagem Molecular , Métodos , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Química , Coloração e RotulagemRESUMO
AIM@#To study the chemical constituents of the fruits of Illicium henryi.@*METHOD@#Chromatographic separations on silica gel, Sephadex LH-20 gel and MCI gel were used to isolate the compounds. The structures were elucidated based on extensive spectroscopic data analyses.@*RESULTS@#Seven compounds were obtained and their structures were identified as 10-benzoyl-cycloparvifloralone (1), cycloparvifloralone (2), 2α-hydroxycycloparviforalone (3), henrylactone B (4), merrillianone (5), henrylactone C (6) and 7, 14-ortholactone- 3-hydroxyfloridanolide (7).@*CONCLUSION@#Compound 1 is a new sesquiterpene lactone. The tested compounds showed weak anti-HBV activities on HBV surface antigen (HBsAg) secretion and HBV e antigen (HBeAg) secretion using Hep G2.2.15 cell line.
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Humanos , Antivirais , Química , Farmacologia , Frutas , Química , Células Hep G2 , Vírus da Hepatite B , Illicium , Química , Estrutura Molecular , Extratos Vegetais , Química , Farmacologia , Sesquiterpenos , Química , FarmacologiaRESUMO
Using a UPLC-MS/MS (MRM) and cocktail probe substrates method, the metabolic fingerprint of the compatibility of Radix Aconite (RA) and Radix Paeoniae Alba (RPA) and its effect on CYP450 enzymes were investigated. These main CYP isoforms include CYP 1A2, CYP 2C, CYP 2E1, CYP 2D and CYP 3A. Compared with the inhibition effect of RA decoctions on CYP450 isoforms, their co-decoctions of RA and RPA with different proportions can decrease RA' inhibition on CYP3A, CYP2D, CYP2C and CYP1A2, but can not reduce RA' effect on CYP2E1. The metabolic fingerprints of RA decoction and co-decoctions with different proportions of RPA in CYP450 of rat liver were analyzed by UPLC-MS. Compared with the metabolic fingerprints of RA decoction, the intensity of diester-diterpenoid aconitum alkaloids decreased significantly, while the intensity of monoester-diterpenoid alkaloids significantly increased in the metabolic fingerprints of co-decoctions of RA and RPA. The results suggest that RA coadministration with RPA increased the degradation of toxic alkaloid and show the effect of toxicity reducing and efficacy enhancing.
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Animais , Ratos , Aconitum , Química , Alcaloides , Química , Cromatografia Líquida de Alta Pressão , Inibidores das Enzimas do Citocromo P-450 , Química , Medicamentos de Ervas Chinesas , Química , Fígado , Metaboloma , Paeonia , Química , Espectrometria de Massas em TandemRESUMO
Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of mesaconitine in rat liver microsomes were identified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4) containing 0.5 gL-1 microsomal protein and 50 micro molL-1 mesaconitine was prepared. The above reaction mixture was divided into six groups, and the volume of each group was 200 micro L. The incubation mixture was pre-incubated at 37 degrees C for 2 min and the reactions were initiated by adding NADPH generating system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was added to each group to stop the reaction. The metabolites of mesaconitine were investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were found in the incubation system. The structures were characterized according to the data from MS/MS spectra and literatures. The metabolic reactions of mesaconitine in rat liver microsomes included the demethylation, deacetylation, dehydrogenation and hydroxylation. The major metabolic pathways of mesaconitine in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP) isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D), diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C), separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were also more important CYP isoforms for the metabolism reactions of mesaconitine, but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver microsomes.
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Animais , Masculino , Ratos , Aconitina , Metabolismo , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A , Metabolismo , Inibidores do Citocromo P-450 CYP3A , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450 , Metabolismo , Inibidores Enzimáticos , Farmacologia , Cetoconazol , Farmacologia , Redes e Vias Metabólicas , Microssomos Hepáticos , Metabolismo , Quinina , Farmacologia , Ratos Sprague-Dawley , Sulfafenazol , Farmacologia , Espectrometria de Massas em TandemRESUMO
<p><b>OBJECTIVE</b>To investigate the clinicopathologic features, immunophenotype, diagnosis and differential diagnosis, and prognostic factors of testicular diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>The clinical and pathologic profiles of 58 cases of testicular DLBCL were investigated.Immunohistochemical stainings and EBER1/2 in situ hybridization were performed on formalin fixed tissues.</p><p><b>RESULTS</b>The average age of the patients was 62.1 years, and the median age was 65 years. The course of disease was short in most of the cases. Clinical stages at diagnosis were mainly stage I or II (87.9%, 51/58). Forty eight patients (82.8%) had unilateral testis involvement. Inguinal lymphadenopathy was observed in 12 (20.7%) patients and the other organs were seldom involved. Morphologically, centroblast-like neoplastic cells infiltrated interstitial tissue of testis diffusely and invaded into seminiferous tubules. Tunica albuginea and vessels were involved in 14 (24.1%) and 10 (17.2%) patients, respectively. Immunophenotype analysis showed predominant non-GCB type of DLBCL (48/58, 82.8%) by Hans classification. No EBV infection was detected. Follow-up data were available in 48 (82.8%) patients. Twenty eight patients (58.3%) died of the disease. One-year, 3-year, and 5-year overall survivals were 55.7%, 31.6% and 27.6%, respectively. Age (older than 60 years), B-symptoms, high serum level of LDH, advanced Ann Arbor stage as well as lack of combination of therapy were associated with a poor prognosis.</p><p><b>CONCLUSIONS</b>This large series of testicular DLBCL mainly present with local disease at diagnosis. Most cases show non-GCB immunophenotype. Despite early clinical stage at presentation, the prognosis is poor. Combined chemotherapy postoperation may prolong survival of the patients.</p>
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Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Ciclofosfamida , Usos Terapêuticos , Doxorrubicina , Usos Terapêuticos , Seguimentos , Imunofenotipagem , Fatores Reguladores de Interferon , Metabolismo , Lactato Desidrogenases , Metabolismo , Metástase Linfática , Linfoma Difuso de Grandes Células B , Tratamento Farmacológico , Alergia e Imunologia , Patologia , Cirurgia Geral , Estadiamento de Neoplasias , Neprilisina , Metabolismo , Orquiectomia , Prednisona , Usos Terapêuticos , Proteínas Proto-Oncogênicas c-bcl-6 , Metabolismo , Taxa de Sobrevida , Neoplasias Testiculares , Tratamento Farmacológico , Alergia e Imunologia , Patologia , Cirurgia Geral , Vincristina , Usos TerapêuticosRESUMO
Effects of six kinds of Chinese herb extracts, including Folium Crataegi extract, Herba Epimedii extract, Folium Acanthopanacis Senticosi extract, Trifolium pratense L. extract, Folium Ginkgo extract and Radix Puerariae extract, on the activities of CYP450 isozymes (CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A) in rat hepatic microsomals were studied by using a UPLC-MS/MS (MRM) and cocktail probe substrates method. The results showed that effects of six kinds of Chinese herb extracts on each CYP450 isozyme activity were inhibitory. The IC50 of Folium Crataegi extract for the inhibition of rat microsomal CYP2D activity was only for 4.04 microg x mL(-1), which showed the highest inhibition; Trifolium pratense L. extract had strong inhibitory action to CYP2D, the IC50 value was 5.73 microg x mL(-1); Folium Crataegi extract also had strong inhibitory action on CYP2E1, the IC50 value was 10.91 microg x mL(-1). Furthermore, the IC50 of Folium Ginkgo extract for the inhibition of rat microsomal CYP3A, 2D, 2E1 activities were 45.12, 35.45 and 22.41 microg x mL(-1), respectively, and the IC50 of Folium Acanthopanacis Senticosi extract on the inhibition of rat microsomal CYP2E1 activity was 32.89 microg x mL(-1). In addition, mechanism of inhibition experimental results showed that the inhibiting abilities of Folium Crataegi extract and Radix Puerariae extract on each CYP450 isozyme increased with the increasing of the preincubation time, therefore, the inhibitory effects were a mechanism-based inhibition.