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1.
J Cell Mol Med ; 24(1): 1141-1145, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31749282

RESUMO

The identification of lymph node metastases is important for the diagnosis, treatment and prognosis of patients with lung cancer. We found DDX49 was associated with the lymph node metastases in lung cancer by the Akt/ß-catenin pathway. Transcriptome sequencing, bioinformatics analysis, quantitative RT-PCR, cell transfection and the Cancer Genome Atlas (TCGA) data set were used to identify DDX49 responsible for lymph node metastases. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to explore the possible molecular mechanism in experimental cell. The DDX49 gene was correlated significantly with lymph node metastases of lung cancer. The knockdown of DDX49 inhibited the cell proliferation and migration in PC-9 and H460 cells. The mechanism research found downexpression of DDX49 decreased the Akt/ß-catenin pathway in lung cancer cell. In vivo experiments showed that DDX49 promoted the proliferation and metastases of lung cancer cells by increasing the Akt/ß-catenin pathway. These findings suggested that DDX49 may be useful as a novel biomarker of lymph node metastases and therapeutic target for lung cancer metastasis.


Assuntos
Biomarcadores Tumorais/metabolismo , Movimento Celular , RNA Helicases DEAD-box/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , RNA Helicases DEAD-box/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Camundongos , Camundongos Nus , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Hum Genomics ; 13(1): 1, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606250

RESUMO

BACKGROUND: Recent advances in semiconductor sequencing platform (SSP) have provided new methods for preimplantation genetic diagnosis/screening (PGD/S). The present study aimed to evaluate the applicability and efficiency of SSP in PGD/S. METHODS: The artificial positive single-cell-like DNAs and normal single-cell samples were chosen to test our semiconductor sequencing platform for preimplantation genetic diagnosis/screening (SSP-PGD/S) method with two widely used whole-genome amplification (WGA) kits. A total of 557 single blastomeres were collected from in vitro fertilization (IVF) couples, and their WGA products were processed and analyzed by our SSP-PGD/S method in comparison with array comparative genomic hybridization (array-CGH). RESULTS: Our SSP-PGD/S method indicated high compatibilities with two commercial WGA kits. For 557 single blastomeres, our method with four million reads in average could detect 24-chromosome aneuploidies as well as microdeletion/microduplication of the size over 4 Mb, providing 100% consistent conclusion with array-CGH method in the classification of whether it was transplantable. CONCLUSIONS: Our studies suggested that SSP-PGD/S represents a valuable alternative to array-CGH and brought PGD/S into a new era of more rapid, accurate, and economic.


Assuntos
Blastômeros/fisiologia , Diagnóstico Pré-Implantação/métodos , Sequenciamento Completo do Genoma/métodos , Aneuploidia , Blastômeros/citologia , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Feminino , Fertilização in vitro , Humanos , Masculino , Semicondutores , Aberrações dos Cromossomos Sexuais , Análise de Célula Única/instrumentação , Análise de Célula Única/métodos , Sequenciamento Completo do Genoma/instrumentação
3.
Am J Obstet Gynecol ; 222(2): 185.e1-185.e17, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31394068

RESUMO

BACKGROUND: Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE: In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN: In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS: As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION: Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.


Assuntos
Hemoglobinas Anormais/genética , Hidropisia Fetal/diagnóstico , Amniocentese , Teorema de Bayes , Ácidos Nucleicos Livres , Amostra da Vilosidade Coriônica , Cordocentese , Síndrome de Down/diagnóstico , Feminino , Genótipo , Heterozigoto , Humanos , Hidropisia Fetal/genética , Teste Pré-Natal não Invasivo , Gravidez , Sensibilidade e Especificidade , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Talassemia alfa/diagnóstico , Talassemia alfa/genética
4.
J Transl Med ; 17(1): 124, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975179

RESUMO

BACKGROUND: Noninvasive prenatal screening (NIPS) based on cell-free fetal DNA (cffDNA) has rapidly been applied into clinic. However, the reliability of this method largely depends on the concentration of cffDNA in the maternal plasma. The chance of test failure results or false negative results would increase when cffDNA fraction is low. In this study, we set out to develop a method to enrich the cffDNA for NIPS based on the size difference between cell-free DNA (cfDNA) of fetal origin and maternal origin, and to evaluate whether the new NIPS method can improve the test quality. METHODS: We utilized 10,000 previous NIPS data to optimize a size-selection strategy for enrichment. Then, we retrospectively performed our new NIPS method with cffDNA enrichment on the 1415 NIPS samples, including 1404 routine cases and 11 false negative cases, and compared the results to the original NIPS results. RESULTS: The 10,000 NIPS data revealed the fetal fraction in short cfDNA fragments (< 160 bp) is significantly higher. By using our new NIPS strategy on the 1404 routine cases, the fetal fraction increased from 11.3 ± 4.2 to 22.6 ± 6.6%, and the new method performed a significant decrease of test-failure rate (0.1% vs 0.7%, P < 0.01). Moreover, in 45.5% (5/11) of the false negative cases, fetal trisomies were successfully detected by our new NIPS method. CONCLUSIONS: We developed an effective method to enrich cffDNA for NIPS, which shows an increased success rate and a reduced chance of false negative comparing to the ordinary NIPS method.


Assuntos
Ácidos Nucleicos Livres/genética , Feto/metabolismo , Diagnóstico Pré-Natal/métodos , Reações Falso-Negativas , Estudos de Viabilidade , Feminino , Humanos , Masculino , Gravidez
5.
Nature ; 490(7418): 49-54, 2012 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-22992520

RESUMO

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.


Assuntos
Adaptação Fisiológica/genética , Exoesqueleto/crescimento & desenvolvimento , Crassostrea/genética , Genoma/genética , Estresse Fisiológico/fisiologia , Exoesqueleto/química , Animais , Proteínas Reguladoras de Apoptose/genética , Elementos de DNA Transponíveis/genética , Evolução Molecular , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Genes Homeobox/genética , Genômica , Proteínas de Choque Térmico HSP70/genética , Humanos , Larva/genética , Larva/crescimento & desenvolvimento , Espectrometria de Massas , Anotação de Sequência Molecular , Dados de Sequência Molecular , Polimorfismo Genético/genética , Sequências Repetitivas de Ácido Nucleico/genética , Análise de Sequência de DNA , Estresse Fisiológico/genética , Transcriptoma/genética
6.
Proc Natl Acad Sci U S A ; 112(47): 14670-5, 2015 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-26554006

RESUMO

Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.


Assuntos
Aberrações Cromossômicas/embriologia , DNA/sangue , Feto/anormalidades , Diagnóstico Pré-Natal/métodos , Semicondutores , Análise de Sequência de DNA/métodos , Sistema Livre de Células , Deleção Cromossômica , Duplicação Cromossômica , Hibridização Genômica Comparativa , Feminino , Humanos , Peso Molecular , Gravidez
7.
Nature ; 479(7372): 223-7, 2011 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-21993625

RESUMO

The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.


Assuntos
Adaptação Fisiológica/genética , Genoma/genética , Longevidade/genética , Ratos-Toupeira/genética , Ratos-Toupeira/fisiologia , Envelhecimento/genética , Sequência de Aminoácidos , Animais , Regulação da Temperatura Corporal/genética , Dióxido de Carbono/análise , Dióxido de Carbono/metabolismo , Ritmo Circadiano/genética , Escuridão , Genes/genética , Instabilidade Genômica/genética , Genômica , Humanos , Canais Iônicos/genética , Longevidade/fisiologia , Masculino , Proteínas Mitocondriais/genética , Dados de Sequência Molecular , Mutagênese/genética , Oxigênio/análise , Oxigênio/metabolismo , Paladar/genética , Transcriptoma/genética , Proteína Desacopladora 1 , Percepção Visual/genética
8.
Proc Natl Acad Sci U S A ; 111(20): 7415-20, 2014 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-24799683

RESUMO

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.


Assuntos
Aneuploidia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 18 , Análise Custo-Benefício , Síndrome de Down/diagnóstico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Humanos , Cariotipagem , Masculino , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Semicondutores , Sensibilidade e Especificidade , Trissomia/diagnóstico , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18
9.
Plant Cell Environ ; 39(6): 1381-92, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26679011

RESUMO

Receptor-like cytoplasmic kinases (RLCKs) represent a large family of proteins in plants. However, few RLCKs have been well characterized. Here, we report the functional characterization of four rice RLCKs - OsRLCK57, OsRLCK107, OsRLCK118 and OsRLCK176 from subfamily VII. These OsRLCKs interact with the rice brassinosteroid receptor, OsBRI1 in yeast cell, but not the XA21 immune receptor. Transgenic lines silenced for each of these genes have enlarged leaf angles and are hypersensitive to brassinolide treatment compared to wild type rice. Transgenic plants silenced for OsRLCK57 had significantly fewer tillers and reduced panicle secondary branching, and lines silenced for OsRLCK107 and OsRLCK118 produce fewer seeds. Silencing of these genes decreased Xa21 gene expression and compromised XA21-mediated immunity to Xanthomonas oryzae pv. oryzae. Our study demonstrates that these OsRLCKs negatively regulate BR signalling, while positively regulating immune responses by contributing to the expression of the immune receptor XA21.


Assuntos
Oryza/crescimento & desenvolvimento , Proteínas de Plantas/fisiologia , Resistência à Doença/fisiologia , Inativação Gênica/fisiologia , Oryza/enzimologia , Oryza/imunologia , Filogenia , Plantas Geneticamente Modificadas , Transdução de Sinais/fisiologia , Estresse Fisiológico , Xanthomonas
10.
Front Med (Lausanne) ; 9: 1011366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36590958

RESUMO

Introduction: This study aimed to determine the correlation between fetal fraction (FF) of cell-free DNA (cf-DNA) and pregnancy complications related to placental dysfunction in Twin Pregnancy. Methods: This retrospective cohort study analyzed twin pregnant women who underwent non-invasive prenatal testing (NIPT) at 12+0-26+6 weeks of gestation from April 2017 to April 2021. Low fetal fraction (LFF) was defined individually as less than the 25th, 10th, 5th, and 2.5th percentile among all fetal fractions in the cohort. Primary outcomes included gestational hypertension (GH), preeclampsia (PE), gestational diabetes mellitus (GDM), and small for gestational age (SGA). Logistic regression analysis was used to assess the relationship between LFF and pregnancy complications. Results: A total of 500 twin pregnancies (male-male twins, 245; female-female twins, 255) were included in this study. In LFF group (FF < 25th percentiles), maternal BMI was significantly higher than FF > 75th percentiles (23.6 kg/m2 vs. 21.3 kg/m2; P < 0.001). The risk of SGA increased gradually from FF < 25th percentiles [adjusted odds ratio (OR), 1.71; 95% confidence interval (CI), 1.07-2.99; P = 0.016] to FF < 2.5th percentiles (adjusted OR, 4.44; 95% CI,1.33-14.82; P < 0.015). In addition, the risks of SGA in both fetuses were higher than the risks of at least one fetus SGA in LFF group. LFF had no correlation with GH, PE, and GDM in twin pregnancy. Conclusion: LFF has a strong association with increased risk of SGA in twin pregnancy. Moreover, FF of cf-DNA may provide a new idea for the early screening of diseases related to placental dysfunction in twin pregnancy.

11.
Mol Med Rep ; 24(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34109425

RESUMO

Cancer metastasis and recurrence are major causes of poor survival in patients with colorectal cancer (CRC). Therefore, the biological behavior of microRNA (miR)­451 in CRC deserves further investigation. Reverse transcription­quantitative PCR was applied to measure the relative expression of miR­451 in blood serum specimens from patients with CRC and CRC cells. In vitro, HCT116 cells were transfected with miR­451 mimics, a miR­451 inhibitor, or SAMD4B plasmids. Proliferation, migration and apoptosis were measured using CCK­8, Transwell assays and flow cytometry, respectively. Luciferase reporter assay was used to identify targets of miR­451 and western blotting performed to explore the internal mechanisms of miR­451 regulation. In vivo, the effect of miR­451 and SAMD4B plasmids on tumor growth was analyzed using a nude mouse xenograft model. Results indicated that serum miR­451 expression was lower in patients with CRC compared with healthy controls. Patients with elevated expression of miR­451 had longer survival times compared with those with low expression. Overexpression of miR­451 inhibited proliferation and migration, promoted apoptosis and enhanced the sensitivity of CRC cells to chemotherapy. SAMD4B was identified as a direct target of miR­451 using miRNA target prediction programs and dual luciferase reporter assay validated the binding site of miR­451 in the 3­'UTR region of SAMD4B. Further studies confirmed that miR­451 inhibited CRC progression via targeting SAMD4B. Results indicated that miR­451 is essential for blocking tumor growth via targeting SAMD4B in vivo and in vitro. The miR­451/SAMD4B axis may serve as a novel therapeutic target in patients with CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Nus , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Int J Clin Exp Pathol ; 14(1): 9-23, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33532019

RESUMO

Disease progression after curative surgery is still the main challenge for colorectal cancer (CRC). Identifying biomarkers and precise mechanisms in CRC disease progression is necessary for therapeutic improvement. As a transcription factor, ZEB1 promotes malignancy, but the precise mechanism by which ZEB1-dependent transcriptional regulation remains largely undefined. In this study, the transcriptional regulation of lysyl oxidase-like 2 (LOXL2) by ZEB1 in CRC was investigated. Our data show that ZEB1 enhanced LOXL2 transcription through direct binding to its promoter. The gain of function assays of ZEB1 showed increased cell proliferation, migration, and invasion. The inhibition of LOXL2 impaired the invasion and migratory ability of CRC cells, but had no effect on cell proliferation in vitro and in vivo. Immunohistochemical staining of tumor tissues indicated that elevated ZEB1/LOXL2 expression was significantly associated with lymph node metastasis and TNM stage. More importantly, elevated ZEB1/LOXL2 expression was an independent prognostic factor in CRC patients. These findings provide a molecular basis for the promotion of an invasive cancer phenotype by ZEB1-LOXL2 overexpression. Our results identify ZEB1/LOXL2 as a prognostic biomarker and potential therapeutic target against progression of CRC.

13.
Onco Targets Ther ; 13: 9657-9666, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061447

RESUMO

BACKGROUND: Recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is a difficult challenge for physicians, especially when patients have been treated with external beam radiotherapy. The purpose of this study was to assess the clinical efficacy and safety of computed tomography (CT)-guided iodine-125 brachytherapy as a palliative treatment for R/M HNSCC. METHODS: From May 2011 to July 2018, we enrolled 87 patients with R/M HNSCC who had previously received external beam radiotherapy. Among these patients, 43 successfully underwent CT-guided iodine-125 brachytherapy and chemotherapy (group A); 44 patients who only received chemotherapy (group B) were matched with patients in group A. Patients' pain score, Eastern Cooperative Oncology Group (ECOG) score, tumor compression symptoms, and side effects of iodine-125 implantation were recorded. Clinical follow-up was performed to assess progression-free survival (PFS) and overall survival (OS). RESULTS: Both groups of patients completed the treatment and were followed up for 9-66 months, with a median follow-up time of 44 months. The OS was 51 months (95% CI: 42.93-59.06 months) versus 28 months (95% CI: 23.79-32.21 months) (p < 0.05), the PFS was 10 months (95% CI: 6.15-13.84 months) versus 6 months (95% CI: 4.40-7.59 months) (p < 0.05) in groups A and B, respectively. The RR in group A was 25/43 (58.14%) versus 15/44 (34.10%) in group B (p < 0.05). Compared with group B, patients in group A had lower pain scores, better physical performance, and better improvement of compression symptoms. No serious treatment-related complications were observed in either group of patients. CONCLUSION: Compared with chemotherapy alone, iodine-125 seed implantation combined with chemotherapy was a more effective and safer strategy for R/M HNSCC.

14.
Sci China C Life Sci ; 51(6): 569-74, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18488178

RESUMO

It is of great importance to identify new cancer genes from the data of large scale genome screenings of gene mutations in cancers. Considering the alternations of some essential functions are indispensable for oncogenesis, we define them as cancer functions and select, as their approximations, a group of detailed functions in GO (Gene Ontology) highly enriched with known cancer genes. To evaluate the efficiency of using cancer functions as features to identify cancer genes, we define, in the screened genes, the known protein kinase cancer genes as gold standard positives and the other kinase genes as gold standard negatives. The results show that cancer associated functions are more efficient in identifying cancer genes than the selection pressure feature. Furthermore, combining cancer functions with the number of non-silent mutations can generate more reliable positive predictions. Finally, with precision 0.42, we suggest a list of 46 kinase genes as candidate cancer genes which are annotated to cancer functions and carry at least 3 non-silent mutations.


Assuntos
Perfilação da Expressão Gênica , Genes Neoplásicos , Mutação , Neoplasias/genética , Humanos , Neoplasias/patologia
15.
Onco Targets Ther ; 11: 6617-6624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349295

RESUMO

BACKGROUND: Advanced non-small-cell lung cancer (NSCLC) is a huge challenge for physicians. Traditional chemoradiotherapy is associated with high rates of toxicities, especially when treating gerontal patients. Our study was focused on investigating the safety and efficacy of permanent iodine-125 seed implantation and chemotherapy for the treatment of advanced NSCLC in the elderly. METHODS: Fifty elderly patients with stage III or IV NSCLC at our hospital from January 2011 to June 2017 were treated with the chemotherapy regimens (paclitaxel/cisplatin) and computed tomography (CT)-guided iodine-125 brachytherapy (group A), 50 patients who received chemotherapy consisting of paclitaxel and cisplatin only (group B) were matched-up with the patients in group A. The local response rate was evaluated by CT. Progression-free survival (PFS) and overall survival (OS) data were obtained through clinical follow-up. RESULTS: The patients were followed-up for 3-46 months. With a median follow-up time of 20 months, the OS and PFS were 20 months (95% CI: 19.09-20.90 months) vs 15 months (95% CI: 14.48-15.51 months) (P<0.05) and 13 months (95% CI: 11.96-14.04 months) vs 8 months (95% CI: 7.63-8.37 months) (P<0.05) in group A and group B, respectively. The symptoms of patients in group A were significantly relieved when compared with group B. Severe complications were not observed in either of the groups. CONCLUSION: The combination of iodine-125 seed brachytherapy and chemotherapy is an effective and safe therapy and is superior to chemotherapy alone for advanced NSCLC in the elderly.

16.
Yi Chuan ; 29(9): 1061-6, 2007 Sep.
Artigo em Zh | MEDLINE | ID: mdl-17855254

RESUMO

Breast cancer is one of the most common malignant tumours. However, the existing functional knowledge about the proteins related to the breast cancer is too general to promote the following study. To find their finer functions, we suggest using the function-specific interaction sub-networks by integrating the functional knowledge of Gene Ontology and the protein-protein interaction network. The results show that the proposed approach is able to reliably find finer functions for these proteins with high precision. The predicted finer functions are highly valuable for guiding the follow-up wet-lab re-search to study the molecular mechanism of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Bases de Dados de Proteínas , Proteínas/metabolismo , Animais , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Modelos Teóricos , Ligação Proteica , Proteínas/fisiologia
17.
Front Plant Sci ; 8: 908, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28680425

RESUMO

The brassinosteroid-SIGNALING KINASE (BSK) belongs to the receptor-like cytoplasmic kinase XII subgroup. BSK1 regulates development and immunity in Arabidopsis. However, the function of rice (Oryza sativa) BSK1 is largely unknown. Here, we report that the expression level of OsBSK1-2 is induced after a chitin or fagellin22 (flg22) treatment. Silencing OsBSK1-2 in rice results in compromised responses to chitin- or flg22-triggered immunity and resistance to Magnaporthe oryzae, but does not alter the plant's architecture nor reduce plant responses to brassinosteroid signaling. Our study reveals that OsBSK1-2 functions as a major regulator in rice plant immunity.

18.
Rice (N Y) ; 8(1): 34, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26054238

RESUMO

BACKGROUND: Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent a large class of proteins in regulating plant development and immunity. The LRR-RLK XA21 confers resistance to the bacterial disease caused by the pathogen of Xanthomonas oryzae pv. oryzae (Xoo). Several XA21 binding proteins have been characterized, however the early events governing XA21 signaling have not been fully elucidated. RESULTS: Here we report the identification of one LRR-RLK gene (XIK1) whose expression is induced rapidly upon the infection with the pathogen of Xoo. Expression pattern analysis reveals that XIK1 is preferentially expressed in reproductive leaves and panicles, and that expression is associated with plant development. By using RNA interference (RNAi), we silenced the expression of XIK1 in rice with Xa21 and found that reduced expression of XIK1 compromised disease resistance mediated by XA21. In addition, we found that the expression of the downstream marker genes of pathogen associated molecular pattern (PAMP) triggered immunity (PTI) in rice was compromised in Xa21 plants silenced for XIK1. CONCLUSION: Our study reveals that the LRR-RLK gene XIK1 is Xoo-responsive and positively regulates Xa21-mediated disease resistance.

19.
PLoS One ; 9(4): e95543, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24743270

RESUMO

BACKGROUND: The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing vascular wilt disease is one of the most devastating pathogens of banana (Musa spp.). To understand the molecular underpinning of pathogenicity in Foc, the genomes and transcriptomes of two Foc isolates were sequenced. METHODOLOGY/PRINCIPAL FINDINGS: Genome analysis revealed that the genome structures of race 1 and race 4 isolates were highly syntenic with those of F. oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence associated genes were identified in both Foc genomes, including genes putatively involved in root attachment, cell degradation, detoxification of toxin, transport, secondary metabolites biosynthesis and signal transductions. Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate (Foc4) has evolved with some expanded gene families of transporters and transcription factors for transport of toxins and nutrients that may facilitate its ability to adapt to host environments and contribute to pathogenicity to banana. Transcriptome analysis disclosed a significant difference in transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the banana 'Brazil' in comparison with the vegetative growth stage. Of particular note, more virulence-associated genes were up regulated in Foc4 than in Foc1. Several signaling pathways like the mitogen-activated protein kinase Fmk1 mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway and a pathogenicity associated two-component system were activated in Foc4 rather than in Foc1. Together, these differences in gene content and transcription response between Foc1 and Foc4 might account for variation in their virulence during infection of the banana variety 'Brazil'. CONCLUSIONS/SIGNIFICANCE: Foc genome sequences will facilitate us to identify pathogenicity mechanism involved in the banana vascular wilt disease development. These will thus advance us develop effective methods for managing the banana vascular wilt disease, including improvement of disease resistance in banana.


Assuntos
Proteínas Fúngicas/genética , Fusarium/genética , Fusarium/patogenicidade , Musa/microbiologia , Doenças das Plantas/microbiologia , Transcriptoma/genética , Perfilação da Expressão Gênica , Genoma Fúngico
20.
Nat Genet ; 43(10): 1035-9, 2011 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-21873998

RESUMO

We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.


Assuntos
Brassica rapa/genética , Genoma de Planta , Poliploidia , Arabidopsis/genética , Cromossomos Artificiais Bacterianos/genética , Cromossomos de Plantas/genética , Mapeamento de Sequências Contíguas , Evolução Molecular , Duplicação Gênica , Genes de Plantas , Anotação de Sequência Molecular , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA
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