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1.
Food Chem Toxicol ; 136: 111050, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31843533

RESUMO

The pickled radish can be kept at room temperature for years without spoilage. 2,6-dihydroxyacetophenone (DHAP), 4-hydroxybenzaldehyde (HBA), and 4-hydroxyphenethyl alcohol (4-HPEA) were first found from the pickled radish. The structures of three phenolic compounds were elucidated by analysis of their nuclear magnetic resonance and high-resolution electro-spray ionization mass spectrometry data. All these phenolic compounds showed good free radical scavenging capacity except HBA. Both DHAP and 4-HPEA also showed high ferric reducing ability. DHAP showed good antimicrobial activity against Escherichia coli, Bacillus subtilis, and Canidia albicans. HBA demonstrated antimicrobial activity against E. coli and C. albicans but not B. subtilis. Based on the results of MTT assay, these compounds did not show cytotoxicity to LO2 cell line. All results indicated the pickled radish had antioxidant and antimicrobial phenolic compounds. To the best of our knowledge, this report is the first to answer partially the question of why pickled foods can be kept at room temperature for years without spoilage based on the evidence of three phenolic compounds.

2.
Oncologist ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784489

RESUMO

BACKGROUND: The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one. RESULTS: The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001). CONCLUSION: The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials. IMPLICATIONS FOR PRACTICE: The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.

3.
Oncoimmunology ; 8(12): 1655361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741753

RESUMO

Programmed death-ligand 1 (PD-L1) is a crucial target for lung cancer immunotherapy. In lung cancer patients with high PD-L1 expression, blocking or reducing its expression can inhibit tumor growth. PD-L1 is regulated by signaling pathways, transcription factors and epigenetic factors, such as the GSK3ß/ß-catenin pathway, P53 protein and EMT. In our previous study, succinate dehydrogenase 5 (SDH5) was reported to regulate ZEB1 expression, induce EMT and lead to lung cancer metastasis via the GSK3ß/ß-catenin pathway. It is possible that SDH5 is involved in the mechanisms of PD-L1 regulation.In the present study, we observed a negative correlation between the expression of PD-L1 and SDH5 in vivo and in vitro. The examination of patient tissues also confirmed our results. Furthermore, we also found that SDH5 could reverse PD-L1 expression by the GSK3ß/ß-catenin/ZEB1 pathways. All these results reveal that SDH5 regulates PD-L1 expression and suggest that SDH5 can be used as a marker to predict tumor immune micro-states and provide guidance for clinical immunotherapy.

4.
Theranostics ; 9(22): 6380-6395, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588224

RESUMO

Radiotherapy is an effective treatment for lung cancer but lacks a reliable prediction method. Cell-free nucleic acids in plasma have been reported as a novel tumor marker. Here, we evaluate circulating succinate dehydrogenase 5 (SDH5) mRNA in plasma and SDH5 protein in tumors, assess their predictive value in lung cancer patients undergoing radiotherapy, and explore the underlying mechanisms. Methods: SDH5 expression was measured in peripheral blood samples and fresh tumor specimens from 208 non-small cell lung cancer (NSCLC) patients and correlated with clinical outcomes. SDH5 knockout mice and human xenograft mice were used to evaluate radiosensitivity. Cell growth, apoptosis, and the DNA damage response were assessed. Relevant RNA and protein levels were analyzed by qRT-PCR and Western blotting. Immunoprecipitation and GST pulldown assays were performed to detect protein-protein interactions. Polyubiquitination of p53 was examined by an in vitro ubiquitination assay. Results: Plasma and tumor SDH5 mRNA levels were positively correlated (rho=0.894, P<0.001). Patients with relatively low SDH5 levels in plasma (0.47, 0.12-0.89) and tumors (3.85, 0.96-7.23) had a better prognosis after radiotherapy (median PFS: 30.0 versus 15.0 months, hazard ratio: 0.276, 95% CI: 0.201-0.379, P<0.001). In SDH5 knockout mice, the lung epithelial cells exhibited increased DNA damage after radiation. In human lung xenograft mice, SDH5-deficient tumors had a smaller volume after radiotherapy. Furthermore, SDH5 depletion inhibits p53 degradation via the ubiquitin/proteasome pathway, which promotes apoptosis and enhances radiosensitivity in NSCLC. Conclusion: Our findings provide a novel noninvasive method for prediction of response to radiotherapy and may have significant implications for cancer radiotherapy.

6.
Sci Total Environ ; 688: 521-528, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31254817

RESUMO

Emiliania huxleyi (Coccolithophore) plays a prominent role in the global carbon cycle and in climate processes. The annual collapse of massive E. huxleyi blooms in the marine environment has been shown to be frequently linked to viral control. These host-virus interactions shape the evolution and dynamics of oceanic microscale ecosystems, yet we still understand little of the molecular mechanism of these virus-mediated processes. Here, we present a detailed characterization of the lipidome of E. huxleyi BOF92 strain, both of uninfected cells and those infected with its specific lytic virus EhV-99B1. Non-targeted lipidomics analysis was performed in order to evaluate the dynamic alterations underlying virus-induced metabolic remodeling. The host lipidome (both lipid content and composition) significantly changed in response to the viral infection. The most statistically significant differential lipids were screened as potential biomarkers for assessing E. huxleyi population sensitivity to EhV infection. Our results reveal that the remodeling of lipid metabolism that underlies the pathogenesis of this infection primarily involved sphingolipid, glycerolipid and fatty acid metabolic pathways. Our study provides insights into how viruses shape their hosts metabolism to support their unique life cycle and a lipid-based chemical arms race during host-virus dynamic interactions in a marine environment.


Assuntos
Haptófitas/virologia , Modelos Biológicos , Ciclo do Carbono , Ecossistema , Oceanos e Mares
7.
J Med Syst ; 43(8): 236, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209662

RESUMO

In order to make a deep analysis of depression, the construction and recognition of functional brain network model based on depression is mainly studied. Firstly, the relevant information of the subjects is introduced in turn. The data of fMRI (functional magnetic resonance imaging) are pretreated, static and dynamic functional connections are analyzed, statistical analysis and testing are carried out, and then the results are analyzed and discussed. The results show that static functional connectivity provides a new research perspective and means for further understanding the connection patterns of brain functional networks in unipolar depression and bipolar depression. Dynamic functional connectivity analysis (DFA) extends the previous studies on unipolar depression and bipolar depression, and provides a potential biological marker for clinical identification of unipolar depression and bipolar depression.


Assuntos
Transtorno Bipolar , Encéfalo/diagnóstico por imagem , Modelos Biológicos , Rede Nervosa , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
8.
J Ethnopharmacol ; 241: 111980, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31146000

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pinellia pedatisecta Schott (PPS)is a traditional Chinese medicine functioning as reducing swelling and drying dampness. Pinellia pedatisecta Schott extract (PE) has been confirmed to suppress cervical tumor growth and modulate the antitumor CD4+T helper immunity towards Th1. AIMS: To explore the roles of PE in modulating tumor-associated dendritic cell (TADC) activation and function. METHODS: For in vivo studies, HPV+TC-1 mouse tumor models were conducted and treated with PE for 3 weeks (10 mg/kg/d or 20 mg/kg/day). The immune profiles of spleen, tumor-draining lymph nodes (TDLNs), tumor and serum were analyzed by flow cytometry and multiplexed bead-based immunoassay. For in vitro studies, TADCs were generated by tumor-conditioned medium and treated with PE solution. The maturation and function of TADCs were evaluated by flow cytometry, ELISA, mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) assay. Furthermore, the effect of PE on SOCS1 pathway was examined by western blotting and real time PCR. RESULTS: PE upregulated the expression of major histocompatibility complex class II (MHCII) and costimulatory molecules CD80 and CD86 on TADCs and promoted IL-12 secretion from TADCs. In addition, PE-treated TADCs promoted the proliferation of CD4+ and CD8+ T cells and induced the differentiation of IFN-γ+CD4+ and GZMB+CD8+ T cells. PE-treated TADCs also elicited a more powerful antigen-specific cytotoxic T lymphocyte (CTL) response. Furthermore, PE treatment in vivo enhanced the proliferation, activated the functional ability (increased Ki67, CD137, GZMB or IFN-γ, TNF-α expression) and reversed the exhaustion (impaired CD95 or PD-1 expression) of antitumor T cells. Mechanistically, PE inhibited SOCS1-restrained JAK2 activation in TADCs. CONCLUSIONS: PE efficiently restored the immature status of TADCs and enhanced their function as antigen-presenting cells to further elicit antitumor Th1 and CTL responses, suggesting that PE may be a potential immunomodulatory drug for cancer treatment.


Assuntos
Células Dendríticas/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Neoplasias/imunologia , Pinellia , Extratos Vegetais/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Feminino , Fatores Imunológicos/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Extratos Vegetais/uso terapêutico
9.
BMJ Open ; 9(4): e026527, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015272

RESUMO

OBJECTIVES: Our aim was to assess the release level of heparin-binding protein (HBP) in sepsis and septic shock under the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). DESIGN: Prospective cohort study. SETTING: A general teaching hospital in China. PARTICIPANTS: Adult infected patients with suspected sepsis and people who underwent physical examination were included. According to the health status and severity of illness, the research subjects were divided into healthy, local infection, sepsis non-shock and septic shock under Sepsis-3 definitions. MAIN OUTCOME MEASURES: Plasma levels of HBP, procalcitonin (PCT), C reactive protein (CRP) and complete blood count were detected in all subjects. Single-factor analysis of variance was used to compare the biomarker levels of multiple groups. A receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of each marker. RESULTS: HBP levels were significantly higher in patients with sepsis non-shock than in those with local infections (median 49.7ng/mL vs 11.8 ng/mL, p<0.01) at enrolment. Moreover, HBP levels in patients with septic shock were significantly higher than in patients with sepsis without shock (median 153.8ng/mL vs 49.7 ng/mL, p<0.01). The area under the ROC curve (AUC) of HBP (cut-off ≥28.1 ng/mL) was 0.893 for sepsis which was higher than those of PCT (0.856) for a cut-off ≥2.05 ng/mL and of CRP (0.699) for a cut-off ≥151.9 mg/L. Moreover, AUC of HBP (cut-off ≥103.5 ng/mL) was 0.760 for septic shock which was higher than the ROC curve of sequential [sepsis-related] organ failure assessment (SOFA) Score (0.656) for a cut-off ≥5.5. However, there was no significant difference between 28-d survivors (n=56) and 28-d non-survivors (n=37) with sepsis in terms of HBP value (p=0.182). CONCLUSIONS: A high level of HBP in plasma is associated with sepsis, which might be a useful diagnostic marker in patients with suspected sepsis.

10.
Nanoscale Res Lett ; 14(1): 138, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31001703

RESUMO

Tumor metastasis has become a key obstacle to cancer treatment, which causes high mortality. Nowadays, it involves multiple complex pathways, and conventional treatments are not effective due to fewer targets. The aims of the present study were to construct a novel liposome delivery system co-loading a specific PLD inhibitor 5-fluoro-2-indolyldes-chlorohalopemide (FIPI) in combination with antitumor drug doxorubicin (DOX) and functional excipient D-alpha tocopheryl acid succinate (α-TOS) for anti-metastasis. In this study, the liposomes containing three components (DFT-Lip) with different physicochemical properties were successfully prepared by film dispersion method combined with pH-gradient method. Physicochemical parameters such as particles size, potential, encapsulation efficiency, stability, and release profiles were investigated. In vitro and in vivo anti-metastasis effectiveness against highly metastatic breast cancer MDA-MB-231 cell line was evaluated. The liposomes showed uniform particle size (approximately 119 nm), high drug encapsulation efficiency (> 90%), slow release characteristics and stability. In vitro anti-tumor cell metastasis study demonstrated DFT-Lip could greatly inhibit motility, migration and invasion of MDA-MB-231 cells compared to other liposomes, predicting a synergistic anti-tumor metastasis effect between FIPI with α-TOS in liposomes. In vivo anti-metastasis study showed that DFT-Lip prevented the initiation and the progression of metastasis of high metastatic breast cancer. These results suggested that the liposomes containing DOX, FIPI, and α-TOS might be a promising strategy for metastatic tumor therapy in clinics.

11.
Front Med ; 13(4): 438-450, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30826965

RESUMO

Cervical cancer (CC) is the fourth most commonly diagnosed female malignancy and a leading cause of cancer-related mortality worldwide, especially in developing countries. Despite the use of advanced screening and preventive vaccines, more than half of all CC cases are diagnosed at advanced stages, when therapeutic options are extremely limited and side effects are severe. Given these circumstances, new and effective treatments are needed. In recent years, exciting progress has been made in immunotherapies, including the rapid development of immune checkpoint inhibitors. Checkpoint blockades targeting the PD-1/PD-L1 axis have achieved effective clinical responses with acceptable toxicity by suppressing tumor progression and improving survival in several tumor types. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway, including the expression patterns of PD-1/PD-L1 and potential PD-1/PD-L1-related therapeutic strategies for CC.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunoterapia/métodos
12.
J Agric Food Chem ; 67(10): 2926-2935, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30789260

RESUMO

α-L-Rhamnosidase is a glycoside hydrolase capable of removing naringin from citrus juice. However, α-L-rhamnosidases always have broad substrate spectra, causing negative effects on citrus juice. In this study, a α-L-rhamnosidase-expressing fungal strain, JMU-TS529, was identified, and its α-L-rhamnosidase was characterized. As a result, JMU-TS529 was identified as Aspergillus tubingensis via morphological and molecular characteristics. The predicted protein sequence shared an amino acid identity of less than 30% with previously characterized α-L-rhamnosidases. The optimal pH and temperature were 4.0 and 50-60 °C, respectively. Most importantly, the α-L-rhamnosidase showed a strong ability to hydrolyze naringin but scarcely acted on other substrates. Furthermore, the enzyme could efficiently remove naringin from pomelo juice without changing its attractive aroma. These results indicate that the present enzyme represents a new clade of Aspergillus α-L-rhamnosidase that is desirable for debittering citrus juice, providing a better alternative for improving the quality of citrus juice.


Assuntos
Aspergillus/enzimologia , Citrus/química , Sucos de Frutas e Vegetais/análise , Proteínas Fúngicas/química , Glicosídeo Hidrolases/química , Aspergillus/genética , Biocatálise , Estabilidade Enzimática , Manipulação de Alimentos , Frutas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Temperatura Ambiente
13.
Proc Natl Acad Sci U S A ; 116(7): 2488-2493, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30692265

RESUMO

The deposition of PM2.5 (fine particulate matter in air with diameter smaller than 2.5 µm) in lungs is harmful to human health. However, real-time observation on the deposition of particles in the acinar area of the lung is still a challenge in experiments. Here, a fluorescent imaging method is developed to visualize the deposition process with a high temporal and spatial resolution. The observations reveal that the deposition pattern is nonuniform, and the maximum deposition rate in the acinar area differs significantly from the prediction of the widely used average deposition model. The method is also used to find single particles in the kidney and liver, though such particles are commonly believed to be too large to enter the extrapulmonary organs.


Assuntos
Rim/metabolismo , Fígado/metabolismo , Microscopia de Fluorescência/métodos , Material Particulado/farmacocinética , Alvéolos Pulmonares/metabolismo , Poluição do Ar , Animais , Humanos , Exposição por Inalação , Camundongos , Distribuição Tecidual
14.
Int J Mol Sci ; 19(12)2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30487433

RESUMO

Dimercaptosuccinic acid (DMSA) is an oral heavy metal chelator. Although DMSA is the most acceptable chelator in the urinary excretion of toxic elements from children and adults, its defects in plasma binding and the membrane permeability limit its interaction with intracellular elements and affect its efficacy in chelation therapy. Herein, a novel nanocomposite composed of mesoporous silica nanoparticles (MSNs), disulfide bond, and DMSA was synthesized and characterized with a scanning/transmission electron microscope, IR and Raman spectra, and TGA analysis. The in vitro interactions with glutathione (GSH) and cellular uptake assays showed that it was able to be stable in extracellular environments such as in blood, be internalized by cells, and release DMSA inside via GSH-triggered disulfide cleavage reaction. The in vitro adsorption assays showed that MSNs-SH as its intracellular metabolite had strong adsorbability for models of Hg2+ or Pb2+. The hemolysis and cell viability assays showed that it was compatible with blood and cells even at a concentration of 1000 µg·mL-1. All above could not only enable it to be a GSH-responsive drug delivery system (DDS) for DMSA delivery but also to be a solution for its defects and efficacy. Thus, introduction of intelligent DDS might open a new avenue for DMSA-based chelation therapy.


Assuntos
Glutationa/química , Nanocompostos/química , Dióxido de Silício/química , Succímero/química , Linhagem Celular , Sobrevivência Celular/fisiologia , Quelantes/química , Humanos , Microscopia Eletroquímica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman
15.
Carcinogenesis ; 39(12): 1477-1487, 2018 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-30256916

RESUMO

MicroRNA-34a (miR-34a) behaves as a tumor suppressor by decreasing the expression of oncogenes involved in multiple carcinogenic pathways. Intravenous delivery of miR-34a mimics has been investigated in clinical trials as a potential treatment for advanced cancers; however, the effect of miR-34a on cancer immune surveillance is controversial. In the current study, we found that miR-34a plays a dual role in the regulation of major histocompatibility complex class I-related sequence B (MICB) protein, a ligand of the NKG2D receptor. MiR-34a could both induce and reduce MICB expression by upregulating ataxia telangiectasia and Rad3-related (ATR) protein kinase and downregulating the transcription factor E2F1, respectively. The net effect of miR-34a on MICB expression depended on endogenous E2F1 levels. Overexpression of miR-34a promoted MICB expression in hepatocytes and hepatocellular carcinoma (HCC) cells that have low E2F1 levels but not in HCC cells that have high E2F1 levels. In HCC patients, the expression of miR-34a and MICB showed positive correlation in paratumor liver tissues, which have low E2F1 levels, but not in HCC tissues, which have high E2F1 levels. We showed that miR-34a overexpression in non-transformed liver cells enhanced cytolysis and interferon-γ production by NK-92MI cells. Furthermore, higher miR-34a expression in tumor and paratumor tissues was associated with positive and negative outcomes, respectively, in HCC patients. Our findings suggest that miR-34a induces MICB expression in paratumor liver tissues, which may cause liver damage and serious cytokine release syndrome, thus disclosing potential side effects of systemic administration of miR-34a in anticancer therapy.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Hepatócitos/patologia , Antígenos de Histocompatibilidade Classe I/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Regulação para Baixo/genética , Fator de Transcrição E2F1/genética , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Interferon gama/genética , Células Matadoras Naturais , Oncogenes/genética , Regulação para Cima/genética
16.
Oncotarget ; 9(11): 10100-10109, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29515794

RESUMO

Background: Accurate delineation of the gross tumor volumes (GTV) is a prerequisite for precise radiotherapy planning and delivery. Different MRI sequences have different advantages and limitations in their ability to discriminate primary cervical tumor from normal tissue. The purpose of this work is to determine appropriate MRI techniques for GTV delineation for external-beam radiation therapy of locally advanced cervical cancer (LACC). Materials and Methods: GTVs were delineated on the MRI, CT, and PET images acquired for 23 LACC patients in treatment positions to obtain GTVs on CT (GTV-CT), on various MRI sequences including T1 (GTV-T1), T2 (GTV-T2), T1 with fat suppression and contrast (GTV-T1F+), DWI-ADC (GTV-ADC) and on PET were generated using the threshold of 40% of maximum SUV (GTV-SUV40%) as well as SUV of 2.5 (GTV-SUV2.5). MRI, CT and PET were registered for comparison. The GTVs defined by MRI were compared using the overlap ratio (OR) and relative volume ratio (RVR). The union of GTV-T2 and GTV-ADC was generated to represent the MRI-based GTV (GTV-MRI). Results: The differences between GTV-T2 and other MRI GTVs are significant (P < 0.05). The average ORs for GTV-T1, GTV-T1F+, and GTV-ADC related to GTV-T2 were 86.3%, 81.6%, and 61.6% with the corresponding average RVRs 113.8%, 112.3% and 77.2%, respectively. There is no significant difference between GTV-T1 and GTV-T1F+. GTV-ADC was generally smaller than GTV-T2, however, encompassed suspicious regions that are uncovered in GTV-T2 (up to 16% of GTV-T2) because of different imaging mechanisms. There was significant difference between GTV-MRI, GTV-SUV2.5, GTV-SUV40%, and GTV-CT. On average, GTV-MRI is 18.4% smaller than GTV-CT. Conclusions: MRI provides improved visualization of disease over CT or PET for cervical cancer. The GTV from the union of GTV-T2 and GTV-ADC provides a reasonable GTV including tumor region defined anatomically and functionally with MRI and substantially reduces the conventional GTV defined on CT.

17.
Biosci Trends ; 12(1): 24-31, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29553098

RESUMO

In order to elucidate the mechanisms underlying the biobehavioral factors responsible for cervical cancer from the perspective of lncRNAs. Tumor samples were obtained from patients with stage Ib-IIb squamous cervical cancer, which were divided into high- and low-risk groups according to biobehavioral risk factors. A lncRNA + mRNA microarray was performed, and the results were validated using qRT-PCR. Gene ontology (GO), pathway, and lncRNA-mRNA co-expression analysis were performed to predict the potential functions of the differentially expressed transcripts. 1,621 lncRNAs and 1,345 mRNAs were found to be differentially expressed between the high-risk and low-risk groups. The results of the qR-TPCR validation were in 100% agreement with the microarray analysis results. GO analysis revealed that the transcripts showing significantly different expression were mainly associated with various aspects of immune response. Pathway analysis indicated that systemic lupus erythematosus signaling was the most significantly down-regulated pathway in the high-risk group. Co-expression analysis indicated NONHSAT002712, NONHSAT095060, and TCONS_00026535 had significant correlations with ZNF683 and BTLA, which were found to be associated with the GO term "adaptive immune response". The levels of genome-wide lncRNAs are significantly altered in cervical tumors from patients with higher biobehavioral risk factors.


Assuntos
Comportamento , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/psicologia , Análise por Conglomerados , Regulação para Baixo/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Risco , Regulação para Cima/genética
18.
Int J Gynecol Cancer ; 28(5): 903-914, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29561301

RESUMO

BACKGROUND: Angiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer. METHODS: We searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing therapy with conventional chemotherapy alone or no further treatment. Our main outcomes were the progression-free survival (PFS), overall survival (OS), and common adverse events. RESULTS: Fifteen trials were included (N = 8721 participants). For newly diagnosed ovarian cancer, combination treatment with angiogenesis inhibitors and chemotherapy yielded a lower risk of disease progression (hazard ratio [HR], 0.83; 95% confidence interval (CI), 0.71-0.97) and no improved OS (HR, 0.95; 95% CI, 0.86-1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR, 0.72; 95% CI, 0.65-0.81) and OS (HR, 0.84; 95%CI, 0.74-0.96). In recurrent patients, the combined HR was 0.58 (95% CI, 0.52-0.65) for PFS, and for OS, the combined HR was 0.86 (95% CI, 0.79-0.94). We found no significant improvement for either PFS (HR, 0.80; 95% CI, 0.63-1.01) or OS (HR, 1.06; 95% CI, 0.88-1.28) in the pure maintenance therapy.In the overall population, angiogenesis inhibitors increased the incidence of gastrointestinal perforation (risk ratio [RR], 2.57; 95% CI, 1.66-3.97), hypertension (RR, 7.60; 95% CI, 2.79-20.70), arterial thromboembolism (RR, 2.27; 95% CI, 1.34-3.84), proteinuria (RR, 4.31; 95% CI, 2.15-8.64), and complication of wound healing (RR, 1.72, 95% CI, 1.12-2.63). CONCLUSIONS: Combination treatment with angiogenesis inhibitors and chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and recurrent ovarian cancer, with an increased incidence of common adverse events. Conversely, we detected no statistically significant survival benefit in the pure maintenance setting. The main limitation of the review is clinical heterogeneity across the studies.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Feminino , Humanos , Neoplasias Ovarianas/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Int J Biol Macromol ; 111: 1032-1039, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29366890

RESUMO

PEGylation is one of the most promising and extensively studied strategies for improving the properties of proteins as well as enzymic physical and thermal stability. Phospholipase C, hydrolyzing the phospholipids offers tremendous applications in diverse fields. However, the poor thermal stability and higher cost of production have restricted its industrial application. This study focused on improving the stabilization of recombinant PLC by chemical modification with methoxypolyethylene glycol-Succinimidyl Succinate (SS-mPEG, MW 5000). PLC gene from isolate Bacillus cereus HSL3 was fused with SUMO, a novel small ubiquitin-related modifier expression vector and over expressed in Escherichia coli. The soluble fraction of SUMO-PLC reached 80% of the total recombinant protein. The enzyme exhibited maximum catalytic activity at 80 °C and was relatively thermostable at 40-70 °C. It showed extensive substrate specificity pattern and marked activity toward phosphatidylcholine, which made it a typical non-specific PLC for industrial purpose. SS-mPEG-PLC complex exhibited an enhanced thermal stability at 70-80 °C and the catalytic efficiency (Kcat/Km) had increased by 3.03 folds compared with free PLC. CD spectrum of SS-mPEG-PLC indicated a possible enzyme aggregation after chemical modification, which contributed to the higher thermostability of SS-mPEG-PLC. The increase of antiparallel ß sheets in secondary structure also made it more stable than parallel ß sheets. The presence of SS-mPEG chains on the enzyme molecule surface somewhat changed the binding rate of the substrates, leading to a significant improvement in catalytic efficiency. This study provided an insight into the addition of SS-mPEG for enhancing the industrial applications of phospholipase C at higher temperature.


Assuntos
Bacillus cereus/enzimologia , Catálise , Proteínas Recombinantes/química , Fosfolipases Tipo C/química , Bacillus cereus/genética , Estabilidade Enzimática , Escherichia coli/genética , Regulação Enzimológica da Expressão Gênica/genética , Temperatura Alta , Cinética , Polietilenoglicóis/química , Proteínas Recombinantes/genética , Especificidade por Substrato , Ácido Succínico/química , Fosfolipases Tipo C/genética
20.
Arch Microbiol ; 200(3): 413-422, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29184974

RESUMO

Lytic viral infection and programmed cell death (PCD) are thought to represent two distinct death mechanisms in phytoplankton, unicellular photoautotrophs that drift with ocean currents. PCD (apoptosis) is mainly brought about by the activation of caspases, a protease family with unique substrate selectivity. Here, we demonstrated that virus infection induced apoptosis of marine coccolithophorid Emiliania huxleyi BOF92 involving activation of metacaspase. E. huxleyi cells exhibited cell death process akin to that of apoptosis when exposed to virus infection. We observed typical hallmarks of apoptosis including cell shrinkage, associated nuclear morphological changes and DNA fragmentation. Immunoblotting revealed that antibody against human active-caspase-3 shared epitopes with a protein of ≈ 23 kDa; whose pattern of expression correlated with the onset of cell death. Moreover, analysis on two-dimensional gel electrophoresis revealed that two spots of active caspase-3 co-migrated with the different isoelectric points. Phosphatase treatment of cytosolic extracts containing active caspases-3 showed a mobility shift, suggesting that phosphorylated form of this enzyme might be present in the extracts. Computational prediction of phosphorylation sites based on the amino acid sequence of E. huxleyi metacaspase showed multiple phosphorylated sites for serine, threonine and tyrosine residues. This is the first report showing that phosphorylation modification of metacaspase in E. huxleyi might be required for certain biochemical and morphological changes during virus induced apoptosis.


Assuntos
Apoptose , Caspases/metabolismo , Vírus Gigantes/fisiologia , Haptófitas/enzimologia , Fitoplâncton/enzimologia , Sequência de Aminoácidos , Caspases/genética , Sequência Conservada , Fragmentação do DNA , Expressão Gênica , Haptófitas/genética , Haptófitas/ultraestrutura , Haptófitas/virologia , Fosforilação , Processamento de Proteína Pós-Traducional
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