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1.
Clin Immunol ; 212: 108345, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31953149

RESUMO

BACKGROUND: Biomarkers in non-colorectal gastrointestinal (GI) cancer patients receiving immune checkpoint blockades (ICBs) are still limited. METHODS: Data were prospectively collected from a discovery cohort (n = 53) and a validation cohort (n = 107) in patients with non-colorectal GI cancer receiving ICB, as well as a chemotherapy-only cohort (n = 171). System inflammatory markers and derived neutrophil-to-lymphocyte ratio (dNLR) were determined as biomarkers by univariate and multivariate analyses. RESULTS: A higher level of dNLR (cutoff = 3) was associated with shorter overall survival (OS) in discovery and validation cohorts. In pooled cohort, disease control rate (DCR) (28% vs. 48.1%) was associated with dNLR (p = .017). In univariate analysis, original tumor site, tumor histopathology, number of metastases, and dNLR were correlated with OS. In multivariate analysis, higher dNLR level was correlated with reduced OS (10.43 months vs. 4.20 months, p < .001). In chemotherapy-only cohort, dNLR was also correlated with DCR and OS. CONCLUSION: Higher dNLR level was correlated with worse outcomes, suggesting that dNLR may help risk-group stratification and assist disease management strategies as a prognostic biomarker for non-colorectal GI patients receiving ICB.

2.
J Hematol Oncol ; 12(1): 16, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764882

RESUMO

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

4.
Clin Colorectal Cancer ; 17(2): e233-e255, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29305209

RESUMO

BACKGROUND: For most colorectal cancer patients with initial lung metastasis (LM), the only suitable treatments are palliative, including palliative local therapy and pharmacotherapy. We investigated the role of palliative local treatments in prolonging survival and the efficacy of different pharmacotherapies. PATIENTS AND METHODS: After performing a medical record review of 2233 patients with metastatic colorectal cancer, 684 were identified as having LM. Their clinicopathologic characteristics, treatment patterns, and outcomes were analyzed retrospectively. RESULTS: For nonresectable initial LM, patients receiving palliative local therapy had significantly longer median progression-free survival (PFS) and overall survival (OS) than those treated with pharmacotherapy alone: PFS 16.1 months versus 7.4 months (P < .001) and OS 51.8 months versus 23.8 months (P < .001), respectively. Cox multivariate analysis confirmed the survival benefit induced by palliative local therapy. Chemonaive patients receiving single-agent fluoropyrimidine had shorter PFS and longer OS compared to oxaliplatin- or irinotecan-based doublets when used as first-line treatment (PFS 4.8, 7.4, and 7.3 months; and OS 28.7, 21.2, and 20.1 months, respectively); however, these differences were not statistically significant. The addition of targeted agents to cytotoxic drugs prolonged PFS (10.5 vs. 7.2 months, P = .005) but not OS (27.8 vs. 21.2 months, P = .454). Carcinoembryonic antigen level, LM-associated symptoms, extrapulmonary disease, and histopathologic type were independent pretreatment prognostic factors. CONCLUSION: Local treatments of LM may confer a survival benefit in the palliative setting. First-line single-agent fluoropyrimidine may be used in patients with good prognosis.


Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/terapia , Neoplasias Colorretais/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Cuidados Paliativos/métodos , Adenocarcinoma/mortalidade , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Pestic Biochem Physiol ; 142: 155-160, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29107240

RESUMO

Benzoylcyclohexanedione herbicides work by inhibiting 4-hydroxyphenylpyruvate dioxygenase which was the last new target site introduced for herbicides. In an attempt to find new 4-hydroxyphenylpyruvate dioxygenase inhibitors with high efficacy and selectivity, a novel benzoylcyclohexanedione compound SYP-9121 was synthesized and studied in greenhouse and field. In the greenhouse, SYP-9121 showed broad spectrum herbicidal activity and good safety to maize. Its control of barnyard grass, crabgrass, redroot pigweed, purslane, dayflower and night shade was equivalent to that of the commercial herbicide mesotrione. Three field trials in summer maize showed that SYP-9121 could efficiently control both grass and broadleaf weeds with good selectivity. Herbicidal activity of SYP-9121 was comparable to that of mesotrione.


Assuntos
Herbicidas/síntese química , Herbicidas/farmacologia , 4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Herbicidas/química , Estrutura Molecular , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/metabolismo , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/enzimologia , Plantas Daninhas/crescimento & desenvolvimento , Relação Estrutura-Atividade , Zea mays/efeitos dos fármacos , Zea mays/enzimologia , Zea mays/crescimento & desenvolvimento
6.
Exp Parasitol ; 159: 183-206, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26420464

RESUMO

An increasing number of researchers have applied secondary-structure based multiple alignments of rDNA genes in phylogeny. These studies mostly depended on a few valuable divergent domains in LSU and SSU rDNA. Yet other divergent domains, e.g. D1, were poorly investigated and rarely used. However, these domains might contain additional evolutionary data and play a vital role in DNA-based phylogenetic study. Here, we investigated all available D1 sequences of Arachnida taxa and predicted corresponding secondary structures to help identify homologous positions in the D1 region. Long insertions were found exclusive to Eriophyoidea and folded into three newly proposed helices. Non-Acari taxa were all GC rich. In Acari, most Trombidiformes and all Mesostigmata (Parasitiformes) taxa were AT rich and Ixodida (Parasitiformes) GC rich; however there was no consistent base bias in Sarcoptiformes sequences. For Eriophyoid mites, genera Cecidophyopsis and Aceria were both well supported in MP, NJ, ME and ML tress based on D1 sequences, and clusters of Cecidophyopsis species were identical with former study. This demonstrated that the D1 region could act as a valuable molecular marker in phylogenetic reconstruction of Eriophyoidea. Additionally, D1 has been proven suitable in phylogenetic analysis at the family and genus level in Acari, but not in Opiliones.


Assuntos
Aracnídeos/classificação , Aracnídeos/genética , DNA Ribossômico/química , Conformação de Ácido Nucleico , Filogenia , Ácaros e Carrapatos/classificação , Ácaros e Carrapatos/genética , Animais , DNA Ribossômico/genética , Marcadores Genéticos , Ácaros/classificação , Ácaros/genética , Alinhamento de Sequência
7.
Exp Parasitol ; 135(2): 370-81, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23954189

RESUMO

According to base pairing, the rRNA folds into corresponding secondary structures, which contain additional phylogenetic information. On the basis of sequencing for complete rDNA sequences (18S, ITS1, 5.8S, ITS2 and 28S rDNA) of Demodex, we predicted the secondary structure of the complete rDNA sequence (18S, 5.8S, and 28S rDNA) of Demodex folliculorum, which was in concordance with that of the main arthropod lineages in past studies. And together with the sequence data from GenBank, we also predicted the secondary structures of divergent domains in SSU rRNA of 51 species and in LSU rRNA of 43 species from four superfamilies in Acari (Cheyletoidea, Tetranychoidea, Analgoidea and Ixodoidea). The multiple alignment among the four superfamilies in Acari showed that, insertions from Tetranychoidea SSU rRNA formed two newly proposed helixes, and helix c3-2b of LSU rRNA was absent in Demodex (Cheyletoidea) taxa. Generally speaking, LSU rRNA presented more remarkable differences than SSU rRNA did, mainly in D2, D3, D5, D7a, D7b, D8 and D10.


Assuntos
Ácaros e Carrapatos/genética , DNA Ribossômico/química , Conformação de Ácido Nucleico , Trombiculidae/genética , Ácaros e Carrapatos/classificação , Animais , Sequência de Bases , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 18S/genética , RNA Ribossômico 28S/genética , RNA Ribossômico 5,8S/genética , Alinhamento de Sequência
8.
J Zhejiang Univ Sci B ; 13(10): 763-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23024043

RESUMO

To our knowledge, few reports on Demodex studied at the molecular level are available at present. In this study our group, for the first time, cloned, sequenced and analyzed the chitin synthase (CHS) gene fragments of Demodex folliculorum, Demodex brevis, and Demodex canis (three isolates from each species) from Xi'an China, by designing specific primers based on the only partial sequence of the CHS gene of D. canis from Japan, retrieved from GenBank. Results show that amplification was successful only in three D. canis isolates and one D. brevis isolate out of the nine Demodex isolates. The obtained fragments were sequenced to be 339 bp for D. canis and 338 bp for D. brevis. The CHS gene sequence similarities between the three Xi'an D. canis isolates and one Japanese D. canis isolate ranged from 99.7% to 100.0%, and those between four D. canis isolates and one D. brevis isolate were 99.1%-99.4%. Phylogenetic trees based on maximum parsimony (MP) and maximum likelihood (ML) methods shared the same clusters, according with the traditional classification. Two open reading frames (ORFs) were identified in each CHS gene sequenced, and their corresponding amino acid sequences were located at the catalytic domain. The relatively conserved sequences could be deduced to be a CHS class A gene, which is associated with chitin synthesis in the integument of Demodex mites.


Assuntos
Quitina Sintase/genética , Ácaros/enzimologia , Ácaros/genética , Animais , Sequência de Bases , Clonagem Molecular , Primers do DNA/genética , Ácaros/classificação , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie
9.
Parasitol Res ; 111(5): 2109-14, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22903416

RESUMO

Due to the difficulty of DNA extraction for Demodex, few studies dealt with the identification and the phyletic evolution of Demodex at molecular level. In this study, we amplified, sequenced, and analyzed a complete (Demodex folliculorum) and an almost complete (D12 missing) (Demodex brevis) ribosomal DNA (rDNA) sequence and also analyzed the primary sequences of divergent domains in small-subunit ribosomal RNA (rRNA) of 51 species and in large-subunit rRNA of 43 species from four superfamilies in Acari (Cheyletoidea, Tetranychoidea, Analgoidea, and Ixodoidea). The results revealed that 18S rDNA sequence was relatively conserved in rDNA-coding regions and was not evolving as rapidly as 28S rDNA sequence. The evolutionary rates of transcribed spacer regions were much higher than those of the coding regions. The maximum parsimony trees of 18S and 28S rDNA appeared to be almost identical, consistent with their morphological classification. Based on the fact that the resolution capability of sequence length and the divergence of the 13 segments (D1-D6, D7a, D7b, and D8-D12) of 28S rDNA were stronger than that of the nine variable regions (V1-V9) of 18S rDNA, we were able to identify Demodex (Cheyletoidea) by the indels occurring in D2, D6, and D8.


Assuntos
Ácaros e Carrapatos/classificação , Ácaros e Carrapatos/genética , DNA Espaçador Ribossômico/genética , DNA Ribossômico/genética , Filogenia , Análise de Sequência de DNA , Animais , Análise por Conglomerados , Sequência Conservada , DNA Ribossômico/química , DNA Espaçador Ribossômico/química , Variação Genética , Mutação INDEL
10.
Exp Parasitol ; 131(1): 45-51, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22414329

RESUMO

The study for the first time attempted to accomplish 18S ribosomal DNA (rDNA) complete sequence amplification and analysis for three Demodex species (Demodex folliculorum, Demodex brevis and Demodex canis) based on gDNA extraction from individual mites. The mites were treated by DNA Release Additive and Hot Start II DNA Polymerase so as to promote mite disruption and increase PCR specificity. Determination of D. folliculorum gDNA showed that the gDNA yield reached the highest at 1 mite, tending to descend with the increase of mite number. The individual mite gDNA was successfully used for 18S rDNA fragment (about 900 bp) amplification examination. The alignments of 18S rDNA complete sequences of individual mite samples and those of pooled mite samples ( ≥ 1000mites/sample) showed over 97% identities for each species, indicating that the gDNA extracted from a single individual mite was as satisfactory as that from pooled mites for PCR amplification. Further pairwise sequence analyses showed that average divergence, genetic distance, transition/transversion or phylogenetic tree could not effectively identify the three Demodex species, largely due to the differentiation in the D. canis isolates. It can be concluded that the individual Demodex mite gDNA can satisfy the molecular study of Demodex. 18S rDNA complete sequence is suitable for interfamily identification in Cheyletoidea, but whether it is suitable for intrafamily identification cannot be confirmed until the ascertainment of the types of Demodex mites parasitizing in dogs.


Assuntos
DNA Ribossômico/química , Genoma/genética , Ácaros/genética , RNA Ribossômico 18S/genética , Animais , Sequência de Bases , Clonagem Molecular , DNA Ribossômico/isolamento & purificação , Ácaros/classificação , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNA
11.
J Exp Bot ; 61(11): 2923-37, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20497970

RESUMO

Plant height (PH), a crucial trait related to yield potential in crop plants, is known to be typically quantitatively inherited. However, its full expression can be inhibited by a limited water supply. In this study, the genetic basis of the developmental behaviour of PH was assessed in a 150-line wheat (Triticum aestivum L.) doubled haploid population (Hanxuan 10 x Lumai 14) grown in 10 environments (year x site x water regime combinations) by unconditional and conditional quantitative trait locus (QTL) analyses in a mixed linear model. Genes that were expressed selectively during ontogeny were identified. No single QTL was continually active in all periods of PH growth, and QTLs with additive effects (A-QTLs) expressed in the period S1|S0 (the period from the original point to the jointing stage) formed a foundation for PH development. Additive main effects (a effects), which were mostly expressed in S1|S0, were more important than epistatic main effects (aa effects) or QTL x environment interaction (QE) effects, suggesting that S1|S0 was the most significant development period affecting PH growth. A few QTLs, such as QPh.cgb-6B.7, showed high adaptability for water-limited environments. Many QTLs, including four A-QTLs (QPh.cgb-2D.1, QPh.cgb-4B.1, QPh.cgb-4D.1, and QPh.cgb-5A.7) coincident with previously identified reduced height (Rht) genes (Rht8, Rht1, Rht2, and Rht9), interacted with more than one other QTL, indicating that the genetic architecture underlying PH development is a network of genes with additive and epistatic effects. Therefore, based on multilocus combinations in S1|S0, superior genotypes were predicted for guiding improvements in breeding for PH.


Assuntos
Triticum/crescimento & desenvolvimento , Triticum/genética , Água/metabolismo , Cruzamento , Regulação da Expressão Gênica no Desenvolvimento , Haploidia , Locos de Características Quantitativas , Triticum/metabolismo
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