RESUMO
BACKGROUND: This work aimed to investigate the inhibitory effect of regorafenib in combination with ginsenoside on the growth of HepG2 liver cancer cells. METHODS: HepG2 liver cancer cells were divided into blank control group, regorafenib single-drug group, ginsenoside single-drug group, and regorafenib/ginsenoside combination group. Cells in the regorafenib single-drug group were treated with regorafenib at 0.25 mg/L, 0.5 mg/L, and 1 mg/L, respectively, while cells in the ginsenoside single-drug group were treated with ginsenoside at 5.0 mg/L, 10.0 mg/L, and 20.0 mg/L, respectively. HepG2 cell proliferation, expression of survivin mRNA, and the apoptotic effector caspase-3 in HepG2 liver cancer cells were assessed. RESULTS: An inhibitory effect on the growth of HepG2 liver cancer cells was observed for both the single-drug therapies and the combination therapy. The synergistic inhibitory effect presented by the combination therapy was dependent on the gradient concentration and treatment time. RT-qPCR results showed that both regorafenib and ginsenoside significantly reduced the expression of survivin mRNA in HepG2 liver cancer cells and the expression level of survivin mRNA in the regorafenib/ginsenoside combination group was much lower than those in the regorafenib single-drug group and ginsenoside single-drug group. The two drugs demonstrated synergistic inhibitory effect when used in combination. CONCLUSIONS: The findings in this study offered a theoretical insight into clinical use of regorafenib and ginsenoside for treatment of liver cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Caspase 3/biossíntese , Ginsenosídeos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/farmacologia , Piridinas/farmacologia , Survivina/biossíntese , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Ginsenosídeos/administração & dosagem , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Piridinas/administração & dosagem , Survivina/genética , Survivina/metabolismoRESUMO
BACKGROUND: The associations between red and processed meat consumption and esophageal cancer risk remain inconclusive. We performed a systematic review and meta-analysis to analyze these associations. METHODS: We searched PubMed and EMBASE to identify studies published between the databases' dates of inception and May 2019. RESULTS: We ultimately selected 33 eligible studies for analysis. We found that the summary relative risks for the associations between meat consumption and esophageal cancer risk were positive for the case-control studies (P < 0.05), but negative for the cohort studies included in the analysis (P > 0.05). Subtype analysis indicated that red and processed meat consumption was not associated with the risks of esophageal adenocarcinoma (P > 0.05) and esophageal squamous cell carcinoma (P > 0.05) in the cohort studies. CONCLUSIONS: We found case-control but not cohort studies to associate consumption of red and processed meat with the risk of esophageal cancer. Further large prospective studies are needed to validate these findings.
Assuntos
Neoplasias Esofágicas/etiologia , Produtos da Carne/efeitos adversos , Carne Vermelha/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Viés de PublicaçãoRESUMO
PURPOSE: Detecting different molecular markers in primary tumors and metastases may provide therapeutic information. Here we investigated differences between primary tumors and four metastatic sites of lung adenocarcinoma in the biomarkers' features and discussed potential therapeutic implications. METHODS: A total of 228 patients with metastatic lung adenocarcinoma were analyzed for EGFR, KRAS, BRAF and PIK3CA mutations detected by xTAG liquidchip technology (xTAG-LCT), as well as ERCC1, TYMS, RRM1, TUBB3, STMN1, TOP2A and VEGFR1-3 mRNA expression detected by branched DNA-liquidchip technology (bDNA-LCT). RESULTS: Higher rates of low ERCC1 (35.6 vs. 20.3%, P = 0.0105), RRM1 (23.3 vs. 13.0%, P = 0.0437), STMN1 (72.2 vs. 42.8%, P = 0.0000) and high VEGFR2 (34.4 vs. 18.8%, P = 0.0078) mRNA expression were found in EGFR-mutated tumors, suggesting possible benefit from platinum, gemcitabine, taxanes or VEGFR2 inhibitors. Primary lesions showed low ERCC1 (31.6 vs. 18.5%, P = 0.0271), TYMS (17.6 vs. 7.6%, P = 0.0300), TUBB3 (16.9 vs. 7.6%, P = 0.0415), STMN1 (62.1 vs. 42.9%, P = 0.0065) and high TOP2A (48.7 vs. 33.1%, P = 0.0262) mRNA expression and higher KRAS mutations (25.7 vs. 14.1%, P = 0.0350), suggesting platinum, taxanes, pemetrexed, anti-TOP2A agents and resistant to anti-EGFR therapies. Liver metastases showed absence of low TYMS expression, indicating insensitivity to pemetrexed-based regimen. Pleura metastases harbored higher rates of high VEGFR2 expression (50.0 vs. 19.1%, P = 0.0127). Lymph node metastases presented higher rates of high VEGFR2 expression (37.5 vs. 19.1%, P = 0.0253) and EGFR mutations (59.4 vs. 34.4%, P = 0.0011), suggesting use of anti-VEGFR2 and anti-EGFR therapies. CONCLUSION: Molecular profiling of 228 lung adenocarcinomas determined a significant difference between biomarkers such as EGFR and KRAS subtypes at primary and metastatic sites. Our results serve as a reference for individual treatment based on different potential targets in metastatic lung adenocarcinoma directed by molecular profiling.
Assuntos
Adenocarcinoma de Pulmão/secundário , Biomarcadores Tumorais/análise , Neoplasias Pulmonares/patologia , Metástase Neoplásica/patologia , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica/genéticaRESUMO
Circulating tumor cells (CTCs), as cells shed from solid tumor into the vasculature, play a significant role in tumor metastasis. In the peripheral blood, immune cells and stromal cells can interact with CTCs and influence their biological behaviors of survival, proliferation, dissemination, and immune evasion. These peripheral blood cells can evolve synergistically with CTCs to constitute the liquid microenvironment which is essential for tumor progression. Here, we review the mechanisms of peripheral blood cells interacting with CTCs and uncover their effects on both CTCs and tumor metastasis. Then, we introduce the applications of these CTC-associated peripheral blood cells in the clinical setting. Besides, some peripheral blood cell subsets are of additional clinical values to CTCs in cancer diagnosis and prognosis. To improve the clinical utility of CTCs, an integrative analysis of CTCs and associated peripheral blood cells should be advocated for, which could provide a novel insight into tumor biology and offer comprehensive information in cancer diagnosis, prognosis, and therapy efficacy evaluation.
Assuntos
Biomarcadores Tumorais/sangue , Células Sanguíneas/patologia , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Microambiente Tumoral , Humanos , Biópsia Líquida , Neoplasias/sangue , PrognósticoRESUMO
An equilibrium needs to be established by the cellular and acellular components of the ovarian follicle if developmental competence is to be acquired by the oocyte. Both cumulus cells (CCs) and follicular fluid (FF) are critical determinants for oocyte quality. Understanding how CCs and FF influence oocyte quality in the presence of deleterious systemic or pelvic conditions may impact clinical decisions in the course of managing infertility. Given that the functional integrities of FF and CCs are susceptible to concurrent pathological conditions, it is important to understand how pathophysiological factors influence natural fertility and the outcomes of pregnancy arising from the use of assisted reproduction technologies (ARTs). Accordingly, this review discusses the roles of CCs and FF in ensuring oocyte competence and present new insights on pathological conditions that may interfere with oocyte quality by altering the intrafollicular environment.
Assuntos
Células do Cúmulo , Líquido Folicular/fisiologia , Oócitos/fisiologia , Animais , Células do Cúmulo/citologia , Células do Cúmulo/fisiologia , Diabetes Mellitus/patologia , Endometriose/patologia , Feminino , Líquido Folicular/citologia , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/patologia , Obesidade/complicações , Obesidade/patologia , Oócitos/citologia , Infecção Pélvica/complicações , Infecção Pélvica/patologia , Síndrome do Ovário Policístico , GravidezRESUMO
The differentiation deficiencies of osteoclast precursors (pre-OCs) may contribute to osteoporosis. Research on osteoporosis has recently focused on microRNAs (miRNAs) that play crucial roles in pre-OC differentiation. In the current study, we aimed to analyze the expression and function of the glucocorticoid (GC)-associated miRNA-338-3p (miR-338-3p) in osteoclast formation. We found that dexamethasone induced osteoclast differentiation and inhibited miR-338-3p expression. Overexpression of an miR-338-3p mimic in osteoclast precursor cells attenuated GC-induced osteoclast formation and bone resorption, whereas inhibition of miR-338-3p reversed these effects. The expression of the nuclear factor κB ligand RANKL, a potential target gene of miR-338-3p, was inversely correlated with miR-338-3p expression in pre-OCs. Furthermore, we demonstrated that RANKL was directly regulated by miR-338-3p and re-introduction of RANKL reversed the inhibitory effects of miR-338-3p on osteoclast formation and bone resorption. Taken together, these findings demonstrate that miR-338-3p may play a significant role in GC-induced osteoclast differentiation and function by targeting RANKL in osteoclasts.
Assuntos
Reabsorção Óssea/genética , Dexametasona/farmacologia , Glucocorticoides/farmacologia , MicroRNAs/genética , Osteoclastos/efeitos dos fármacos , Ligante RANK/genética , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Bovinos , Diferenciação Celular/efeitos dos fármacos , Técnicas de Cocultura , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Fêmur/patologia , Regulação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Modelos Biológicos , Oligorribonucleotídeos Antissenso/genética , Oligorribonucleotídeos Antissenso/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patologia , Cultura Primária de Células , Ligante RANK/metabolismo , Transdução de SinaisRESUMO
v-myb avianmyeloblastosis viral oncogene homolog (MYB) transcription factors are key regulators of stress responsive gene expression in plants. In this study, the MYB gene, ChiMYB (GenBank accession No. KT948997), was isolated from Chrysanthemum indicum, and was functionally characterized with an emphasis on salinity stress tolerance. The full ChiMYB cDNA sequence (948 bp) encoded a typical R2R3 MYB transcription factor that contained 315 amino acid residues and two MYB domains. The temporal expression pattern of ChiMYB was noted in C. indicum, and the highest level was detected in the roots, followed by leaves and stems. ChiMYB expression was induced by NaCl treatments, and transient expression of the fusion of ChiMYB and green fluorescent protein (GFP) indicated that the protein was targeted to the nuclei of onion epidermal cells. Arabidopsis plants overexpressing ChiMYB displayed improved tolerance to drought and salt stress. When under salt stress conditions, transgenic Arabidopsis plants had higher survival rates than non-transgenic wild-type plants. Chlorophyll content, intercellular CO2 concentration, photosynthetic rate, and stomatal conductance were higher in the transgenic Arabidopsis plants than in non-transgenic control plants. Further investigation revealed that ChiMYB was able to regulate the expression of RD29A, RAB18, COR15, ABI1, and ABA genes, which are involved in salt stress signaling pathways. Our findings demonstrated that ChiMYB is essential for plant responses to salt stress, and it may have great potential for the improvement of salt tolerance in crops.
Assuntos
Chrysanthemum/genética , Proteínas de Plantas/genética , Salinidade , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Arabidopsis/genética , Sequência de Bases , Carotenoides/metabolismo , Clorofila/metabolismo , Chrysanthemum/efeitos dos fármacos , Chrysanthemum/crescimento & desenvolvimento , Clonagem Molecular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Germinação , Proteínas de Fluorescência Verde/metabolismo , Fotossíntese/efeitos dos fármacos , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Alinhamento de Sequência , Cloreto de Sódio/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismoRESUMO
We analyzed the association between polymorphisms in three glutathione S-transferase genes (GSTP1, GSTM1, and GSTT1) and the treatment outcome for advanced non-small cell lung cancer (NSCLC). We recruited 284 NSCLC patients at advanced stage from Department of Radiotherapy in Peace Hospital Attached to Changzhi Medical College between May 2009 and May 2011, who had received cisplatin-based chemotherapy. The GSTP1, GSTM1, and GSTT1 genotyping for was determined using DNA pyrosequencing on an ABI Prism 3100 DNA analyzer. In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes of GSTP1 were associated with lower risk of disease progression compared with the IIe/IIe genotype, and the HRs (95%CIs) were 0.37 (0.18-0.74) and 0.15 (0.06-0.35), respectively. The IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with NSCLC, and the HRs (95%CIs) were 0.52 (0.29-0.92) and 0.37 (0.17- 0.79), respectively No significant association was observed between GSTM1 and GSTT1 polymorphisms and progression-free survival and overall survival in the NSCLC patients. In summary, we suggest that GSTP1 polymorphisms might influence the treatment outcome of advanced NSCLC patients, and our results could help improve individualized therapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Glutationa S-Transferase pi/genética , Adulto , Idoso , Povo Asiático , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/terapia , China , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Feminino , Estudos de Associação Genética , Glutationa Transferase/genética , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do TratamentoRESUMO
Members of the archaeal phylum Bathyarchaeota are widespread and abundant in the energy-deficient marine subsurface sediments. However, their life strategies have remained largely elusive. Here, we provide genetic evidence that some lineages of Bathyarchaeota are acetogens, being capable of homoacetogenesis, a metabolism so far restricted to the domain Bacteria. Metabolic reconstruction based on genomic bins assembled from the metagenome of deep-sea subsurface sediments shows that the metabolism of some lineages of Bathyarchaeota is similar to that of bona fide bacterial homoacetogens, by having pathways for acetogenesis and for the fermentative utilization of a variety of organic substrates. Heterologous expression and activity assay of the acetate kinase gene ack from Bathyarchaeota, demonstrate further the capability of these Bathyarchaeota to grow as acetogens. The presence and expression of bathyarchaeotal genes indicative of active acetogenesis was also confirmed in Peru Margin subsurface sediments where Bathyarchaeota are abundant. The analyses reveal that this ubiquitous and abundant subsurface archaeal group has adopted a versatile life strategy to make a living under energy-limiting conditions. These findings further expand the metabolic potential of Archaea and argue for a revision of the role of Archaea in the carbon cycle of marine sediments.
Assuntos
Acetatos/metabolismo , Archaea/enzimologia , Archaea/genética , Sedimentos Geológicos/microbiologia , Metagenoma , Água do Mar/microbiologia , Acetato Quinase/genética , Archaea/classificação , Archaea/metabolismo , Ciclo do Carbono , DNA Arqueal , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Oxirredução , Peru , Filogenia , RNA Ribossômico 16S , Sulfatos/metabolismoRESUMO
Recombinant human anti-tumor necrosis factor (TNF)-α scFv-Fc was expressed in TKO mutant Arabidopsis thaliana seeds using plant-specific codons. Immunoblotting using a human IgG1 antibody detected the expression of anti-TNF-α proteins in plants. Results from qRT-PCR analysis demonstrated that the time of harvest significantly affected the protein yield and quality. Our results indicate that the Phaseolus vulgaris ß-phaseolin promoter directed anti-TNF-α scFv-Fc expression in A. thaliana seeds, with a maximum yield obtained at 20-days of development. Although the yield of anti-TNF-α scFv-Fc protein was not very high, accumulation of recombinant proteins in seeds is an attractive and simple method that can be used to purify biologically active anti-TNF-α scFv-Fc.
Assuntos
Arabidopsis/genética , Fragmentos Fc das Imunoglobulinas/genética , Sementes/metabolismo , Anticorpos de Cadeia Única/genética , Transgenes , Fator de Necrose Tumoral alfa/imunologia , Arabidopsis/metabolismo , Fragmentos Fc das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/metabolismo , Proteínas Recombinantes , Sementes/genética , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismoRESUMO
Glycine betaine is an important quaternary ammonium compound that is produced in response to several abiotic stresses in many organisms. The synthesis of glycine betaine requires the catalysis of betaine aldehyde dehydrogenase (BADH), which can convert betaine aldehyde into glycine betaine in plants, especially in halotolerant plants. In this study, we isolated the full-length cDNA of BADH from Suaeda corniculata (ScBADH) using reverse transcriptase-polymerase chain reaction and rapid amplification of cDNA ends. Next, we analyzed the expression profile of ScBADH using real-time PCR. The results showed that ScBADH expression was induced in the roots, stems, and leaves of S. corniculata seedlings under salt and drought stress. Next, ScBADH was overexpressed in Arabidopsis, resulting in the transgenic plants exhibiting enhanced tolerance over wild-type plants under salt and drought stress. We then analyzed the levels of glycine betaine and proline, as well as superoxide dismutase (SOD) activity, during salt stress in WT and transgenic Arabidopsis. The results indicated that overexpression of ScBADH produced more glycine betaine and proline, and increased SOD activity under NaCl treatment. Our results suggest that ScBADH might be a positive regulator in plants during the response to NaCl.
Assuntos
Betaína-Aldeído Desidrogenase/genética , Chenopodiaceae/genética , Proteínas de Plantas/genética , Betaína/metabolismo , Betaína-Aldeído Desidrogenase/metabolismo , Chenopodiaceae/enzimologia , Clonagem Molecular , Secas , Regulação da Expressão Gênica de Plantas , Glicina/metabolismo , Proteínas de Plantas/metabolismo , Prolina/metabolismo , Salinidade , Estresse Fisiológico , Superóxido Dismutase/metabolismoRESUMO
To understand the beneficial and harmful bio-effects of extremely low frequency electromagnetic fields, we studied the MAPK/ERK signaling pathway based on the Huang-Ferrell model. The sensitivity analysis method was used to study the influence of the model parameters on the activity of ERK, and to further investigate the key biochemical reactions and proteins. The results of the simulation show that an increase in the reaction rate of MAPK/ERK kinase had little effect on ERK activation and the steady-state molecular number. However, a decrease in the reaction rate of MAPK/ERK kinase significantly affected the trigger time of ERK activation and decreased the steady-state molecular number. Together with the biological significance of ERK activity, our findings indicate that the effects of electromagnetic fields are a result of the decrease in the reaction rate of MAPK/ERK kinase, which eventually determines whether these effects cause physical damage or are beneficial in treatment.
Assuntos
Campos Eletromagnéticos/efeitos adversos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Modelos Teóricos , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , HumanosRESUMO
Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 gene polymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect.
Assuntos
Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único , Proteínas com Domínio T/genética , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , MasculinoRESUMO
Genomic imprinting is an important epigenetic mechanism that has vital effects on fetal growth and development. We observed the differences in four tissues (heart, spleen, liver, and kidney) from dead transgenic cloned goats using hematoxylin and eosin (H&E) staining. Eight imprinted genes in the tissues of dead transgenic cloned and normal goats were analyzed using reverse transcription polymerase chain reaction. H&E staining results from the abortion group indicated the lack of obvious morphological changes in heart and spleen tissues, while inflammatory cell infiltration and glomerular nephritis characteristics were observed in liver and kidney tissues, respectively. Compared to the control group, CDKN1C, H19, IGF2R, and SNRPN were significantly (P < 0.05) overexpressed in the heart tissue of the abortion group, while XIST was significantly reduced. In the liver tissues, CDKN1C and DLK1 expression decreased, while GNAS, H19, IGF2R, PEG3, and XIST expression increased significantly. In the spleen tissues, DLK1 expression increased, while GNAS, H19, IGF2R, PEG3, SNRPN, and XIST expression decreased. In the kidney tissues, CDKN1C, DLK1, GNAS, IGF2R, and PEG3 expression increased, while H19 and XIST expression decreased. The overall expression of imprinted genes was abnormal in different tissues of transgenic cloned goats, and the degree of abnormal genomic imprinting was more severe in the abortion group compared to the death and control groups. These results suggest that abnormal expression of imprinted genes may cause developmental defects in transgenic cloned goats. Moreover, abnormal epigenetic modifications may affect the reprogramming of transgenic donor cells.
Assuntos
Clonagem de Organismos/mortalidade , Epigênese Genética , Genes Letais , Impressão Genômica , Cabras/genética , Lactoferrina/genética , Animais , Animais Geneticamente Modificados , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Feminino , Perfilação da Expressão Gênica , Cabras/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Rim/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Lactoferrina/metabolismo , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Gravidez , Transdução de Sinais , Baço/metabolismo , TransgenesRESUMO
We aimed to investigate the role of XRCC1 codon 194 (Arg>Trp), 280 (Arg>His), and 399 (Arg>Gln) polymorphisms in response to chemotherapy and the overall survival of gastric cancer patients. A total of 172 patients were recruited for our study between January 2010 and March 2012. Genotyping of the three XRCC1 codons was carried out by restriction fragment length polymorphism polymerase chain reaction. By logistic regression analysis, we found that the Trp/Trp genotype of XRCC1 194 (Arg>Trp) showed a stronger association with complete or partial response to chemotherapy compared to the Arg/Arg genotype, and the adjusted odds ratio (95%CI) was 0.17 (0.05-0.58). Moreover, the Trp/Trp genotype was associated with a higher risk of death than that with the Arg/Arg genotype based on multivariate Cox proportional hazard regression analysis, and the adjusted hazard ratio (95%CI) was 4.08 (1.20-14.19). In conclusion, we found that the XRCC1 194 (Arg>Trp) polymorphism was correlated with a better response to chemotherapy and a low risk of death in patients with gastric cancer.
Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ligação a DNA/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Idoso , Idoso de 80 Anos ou mais , Códon , Feminino , Seguimentos , Expressão Gênica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sequência de DNA , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
The authors previously identified plasma plasminogen activator inhibitor-1 (PAI-1) level as a quantitative lung injury biomarker in primary graft dysfunction (PGD). They hypothesized that plasma levels of PAI-1 used as a quantitative trait could facilitate discovery of genetic loci important in PGD pathogenesis. A two-stage cohort study was performed. In stage 1, they tested associations of loci with PAI-1 plasma level using linear modeling. Genotyping was performed using the Illumina CVD Bead Chip v2. Loci meeting a p < 5 × 10(-4) cutoff were carried forward and tested in stage 2 for association with PGD. Two hundred ninety-seven enrollees were evaluated in stage 1. Six loci, associated with PAI-1, were carried forward to stage 2 and evaluated in 728 patients. rs3168046 (Toll interacting protein [TOLLIP]) was significantly associated with PGD (p = 0.006). The increased risk of PGD for carrying at least one copy of this variant was 11.7% (95% confidence interval 4.9-18.5%). The false-positive rate for individuals with this genotype who did not have PGD was 6.1%. Variants in the TOLLIP gene are associated with higher circulating PAI-1 plasma levels and validate for association with clinical PGD. A protein quantitative trait analysis for PGD risk prioritizes genetic variations in TOLLIP and supports a role for Toll-like receptors in PGD pathogenesis.
Assuntos
Biomarcadores/análise , Variação Genética/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/diagnóstico , Locos de Características Quantitativas , Adulto , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Inibidor 1 de Ativador de Plasminogênio/sangue , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/etiologia , Prognóstico , Estudos ProspectivosRESUMO
Zinc (Zn) is important for male mammalian reproduction. In this study, we sought to clarify the role of Zn in heat-induced testicular damage in mice. Eighteen mice were divided into either control (con), heat (heat) and heat plus Zn (H+Zn) treatment groups, and fed diets containing 60 (con and heat groups) or 300 (H+Zn group) mg/kg Zn sulfate for one month. Mice in the con group were then maintained at 25°C, while mice in heat and H+Zn groups were exposed to 40°C for 2 h daily, for eight days. Mouse testes and serum from each animal were analyzed. Zinc levels in serum and testes were positively correlated to Zn feed concentrations. Mice in the heat group had higher testes index than those in the other two groups (7.22 ± 0.75, heat; 4.92 ± 0.20, con; 4.80 ± 0.30 mg/g, H+Zn; P < 0.05). Testicular antioxidant status showed malondialdehyde levels in heat group mice were increased compared to control mice (2.34 ± 0.15 versus 1.55 ± 0.23 nmol/mg protein; P < 0.05), and Cu-Zn superoxide dismutase (SOD) level differed between heat and H+Zn groups (14.04 ± 0.74 versus 18.27 ± 1.53 U/mg protein; P < 0.05). Testicular Cu-Zn SOD protein expression levels were significantly lower in the heat than in the control group (0.30 ± 0.11 versus 1.22 ± 0.13; P < 0.05). These results suggest that dietary Zn may elevate the activity and protein concentration of Cu-Zn SOD, to attenuate testicular oxidative stress induced by heat exposure.
Assuntos
Estresse Oxidativo , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Zinco/farmacologia , Animais , Suplementos Nutricionais , Temperatura Alta/efeitos adversos , Masculino , Malondialdeído/metabolismo , Camundongos , Superóxido Dismutase/genética , Testículo/metabolismo , Regulação para Cima , Zinco/administração & dosagem , Zinco/sangueRESUMO
Numerous studies have evaluated the association between the angiotensin II type-1 receptor (AGTR1) gene A1166C polymorphism and breast cancer risk. However, the specific association is controversial. The aim of the present study was to derive a more precise estimation of the relationship. A comprehensive research was conducted of the PubMed and the Google Scholar databases through February 2015. Data were assessed using STATA version 12.0. Pooled odds ratios with 95%CIs were derived from the fixed-effect or random-effect models. A total of 911 patients with breast cancer and 1284 controls from 5 case-control studies were included in this meta-analysis. The meta-analysis results showed no significant association between the AGTR1 gene A1166C polymorphism and breast cancer risk. Similarly, in the subgroup analysis regarding ethnicity, no associations were observed. Heterogeneity and publication bias were not observed in this meta-analysis. The A1166C polymorphism in the AGTR1 gene may not be a risk factor for breast cancer. Further, large, and well-designed studies are needed to confirm this conclusion.
Assuntos
Neoplasias da Mama/genética , Polimorfismo Genético/genética , Receptor Tipo 1 de Angiotensina/genética , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Modelos Genéticos , Razão de Chances , Fatores de RiscoRESUMO
It has been shown that microRNA-215 (miR-215) is dysregulated in several human malignancies, and this correlates with tumor progression. However, its expression and function in pancreatic cancer is still unclear. The aim of this study was to explore the effects of miR-215 on pancreatic cancer formation and progression. Using quantitative RT-PCR, we detected miR-215 expression in pancreatic cancer cell lines and primary tumor tissues. The association of miR-215 expression with clinicopathological factors and prognosis was also analyzed. We then observed the effects of miR-215 on the biological behavior of pancreatic cancer cells. Lastly, the potential regulatory function of miR-215 on ZEB2 expression was investigated. miR-215 expression levels were significantly downregulated in pancreatic cancer samples and cell lines. Decreased miR-215 expression was significantly associated with large tumor size, advanced TNM stage, lymph node metastasis, vessel invasion, and lower overall survival. Multivariate regression analysis corroborated that downregulation of miR-215 was an independent unfavorable prognostic factor. Overexpression of miR-215 inhibited pancreatic cancer cell proliferation, invasion, and migration; promoted cell apoptosis in vitro; and suppressed tumorigenicity in vivo. Further, ZEB2 was confirmed as a direct target of miR-215 by using a luciferase reporter assay. These findings indicate that miR-215 may act as a tumor suppressor in pancreatic cancer cells, and could serve as a novel therapeutic target for miR-based therapy.
Assuntos
Genes Supressores de Tumor , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Interferência de RNA , Proteínas Repressoras/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Animais , Apoptose/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Proteínas de Homeodomínio/química , Humanos , Masculino , Camundongos , MicroRNAs/química , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Mensageiro/química , RNA Mensageiro/genética , Proteínas Repressoras/química , Carga Tumoral , Homeobox 2 de Ligação a E-box com Dedos de ZincoRESUMO
The basic-region/leucine-zipper (bZIP) family is one of the major transcription factor (TF) families associated with responses to abiotic stresses. Many members of group A in this family have been extensively examined and are reported to perform significant functions in ABA signaling as well as in responses to abiotic stresses. In this study, 10 bZIP factors in carrot were classified into group A based on their DNA-binding domains. The cis-acting regulatory elements and folding states of these 10 factors were analyzed. Evolutionary analysis of the group A members suggested their importance during the course of evolution in plants. In addition, cis-acting elements and the folding state of proteins were important for DNA binding and could affect gene expression. Quantitative RT-PCR was conducted to investigate the stress response of 10 genes encoding the group A factors. Six genes showed responses to abiotic stresses, while four genes showed other special phenomenon. The current analysis on group A bZIP family TFs in carrot is the first to investigate the TFs of Apiaceae via genome analysis. These results provide new information for future studies on carrot.