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1.
Nucleic Acids Res ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643730

RESUMO

Large indels greatly impact the observable phenotypes in different organisms including plants and human. Hence, extracting large indels with high precision and sensitivity is important. Here, we developed IndelEnsembler to detect large indels in 1047 Arabidopsis whole-genome sequencing data. IndelEnsembler identified 34 093 deletions, 12 913 tandem duplications and 9773 insertions. Our large indel dataset was more comprehensive and accurate compared with the previous dataset of AthCNV (1). We captured nearly twice of the ground truth deletions and on average 27% more ground truth duplications compared with AthCNV, though our dataset has less number of large indels compared with AthCNV. Our large indels were positively correlated with transposon elements across the Arabidopsis genome. The non-homologous recombination events were the major formation mechanism of deletions in Arabidopsis genome. The Neighbor joining (NJ) tree constructed based on IndelEnsembler's deletions clearly divided the geographic subgroups of 1047 Arabidopsis. More importantly, our large indels represent a previously unassessed source of genetic variation. Approximately 49% of the deletions have low linkage disequilibrium (LD) with surrounding single nucleotide polymorphisms. Some of them could affect trait performance. For instance, using deletion-based genome-wide association study (DEL-GWAS), the accessions containing a 182-bp deletion in AT1G11520 had delayed flowering time and all accessions in north Sweden had the 182-bp deletion. We also found the accessions with 65-bp deletion in the first exon of AT4G00650 (FRI) flowered earlier than those without it. These two deletions cannot be detected in AthCNV and, interestingly, they do not co-occur in any Arabidopsis thaliana accession. By SNP-GWAS, surrounding SNPs of these two deletions do not correlate with flowering time. This example demonstrated that existing large indel datasets miss phenotypic variations and our large indel dataset filled in the gap.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34465137

RESUMO

Yunnan is the first place where HIV-1 became prevalent in China, and it is also the place with the most complicated HIV-1 genetic diversity in China. On October 23, 2019, a patient newly diagnosed with acquired immunodeficiency syndrome from a hospital in Baosan, Yunnan, was recruited for genetic analysis. Near full-length genome of HIV-1 was amplified from the plasma sample. Phylogenetic analysis revealed that this sequence (BS6F24) has a close relationship with CRF86_BC and a unique recombinant form (KY406739), which was formed by recombination of subtypes B and C. Bootscan analysis confirmed that the first part (HXB2:1022-5832) and last part (HXB2:5833-9120) genomes of BS6F24 had the same recombinant structures as KY406739 and CRF86_BC, respectively. A second-generation recombinant form that originated from CRF86_BC and a unique recombinant form were reported for the first time. This indicates the need for continuous monitoring of the genetic diversity of HIV-1 in Yunnan, China.

4.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801148

RESUMO

Chemotherapeutics are the mainstay treatment for metastatic breast cancers. However, the chemotherapeutic failure caused by multidrug resistance (MDR) remains a pivotal obstacle to effective chemotherapies of breast cancer. Although in vitro evidence suggests that the overexpression of ATP-Binding Cassette (ABC) transporters confers resistance to cytotoxic and molecularly targeted chemotherapies by reducing the intracellular accumulation of active moieties, the clinical trials that target ABCB1 to reverse drug resistance have been disappointing. Nevertheless, studies indicate that ABC transporters may contribute to breast cancer development and metastasis independent of their efflux function. A broader and more clarified understanding of the functions and roles of ABC transporters in breast cancer biology will potentially contribute to stratifying patients for precision regimens and promote the development of novel therapies. Herein, we summarise the current knowledge relating to the mechanisms, functions and regulations of ABC transporters, with a focus on the roles of ABC transporters in breast cancer chemoresistance, progression and metastasis.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/classificação , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Progressão da Doença , Suscetibilidade a Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Família Multigênica , Metástase Neoplásica , Estadiamento de Neoplasias , Relação Estrutura-Atividade
5.
Am J Orthod Dentofacial Orthop ; 159(6): 758-765, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33722409

RESUMO

INTRODUCTION: The objective of this research was to evaluate the reliability of 2 methods (Andrews' Element III analysis and Yonsei transverse analysis) in maxillary transverse deficiency diagnosis. METHODS: Plaster casts and cone-beam computed tomography images of 80 outpatients with skeletal Class I malocclusion (29 males and 51 females, mean age, 20.16 ± 8.22 years) were selected. Maxillary and mandibular width were measured, respectively, and independently by 2 examiners at an interval of 2 weeks, using Andrews' Element III analysis and Yonsei transverse analysis. Intraclass correlation coefficients and Bland-Altman plots of intraexaminer and interexaminer reliability were evaluated. After diagnosis, Cohen's kappa statistics were calculated to evaluate the diagnostic agreement. RESULTS: The intraclass correlation coefficients were all above 0.85, indicating good to excellent reliability. Compared with Andrews' Element III analysis, Yonsei transverse analysis had higher intraexaminer and interexaminer reliability in both maxillary and mandibular width measurements. Thirty-one to 42 of the patients were diagnosed with maxillary transverse deficiency by 2 examiners using 2 methods. The intraexaminer and interexaminer Cohen's kappa values of Yonsei transverse analysis were all higher than those of Andrews' Element III analysis. CONCLUSIONS: Both Andrews' Element III analysis and Yonsei transverse analysis had good to excellent reliability and substantial diagnostic agreement. Yonsei transverse analysis had higher reliability in maxillary and mandibular width measurements and higher diagnostic agreement, compared with Andrews' Element III analysis.


Assuntos
Mandíbula , Dente , Adolescente , Adulto , Criança , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Maxila/diagnóstico por imagem , Reprodutibilidade dos Testes , Adulto Jovem
7.
Plant J ; 104(5): 1410-1422, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33048384

RESUMO

Brassica napus is an important oilseed crop in the world, and the mechanism of seed oil biosynthesis in B. napus remains unclear. In order to study the mechanism of oil biosynthesis and generate germplasms for breeding, an ethyl methanesulfonate (EMS) mutant population with ~100 000 M2 lines was generated using Zhongshuang 11 as the parent line. The EMS-induced genome-wide mutations in M2-M4 plants were assessed. The average number of mutations including single nucleotide polymorphisms and insertion/deletion in M2-M4 was 21 177, 28 675 and 17 915, respectively. The effects of the mutations on gene function were predicted in M2-M4 mutants, respectively. We screened the seeds from 98 113 M2 lines, and 9415 seed oil content and fatty acid mutants were identified. We further confirmed 686 mutants with altered seed oil content and fatty acid in advanced generation (M4 seeds). Five representative M4 mutants with increased oleic acid were re-sequenced, and the potential causal variations in FAD2 and ROD1 genes were identified. This study generated and screened a large scale of B. napus EMS mutant population, and the identified mutants could provide useful genetic resources for the study of oil biosynthesis and genetic improvement of seed oil content and fatty acid composition of B. napus in the future.


Assuntos
Brassica napus/genética , Metanossulfonato de Etila/farmacologia , Mutação , Óleos Vegetais/química , Sementes/química , Brassica napus/efeitos dos fármacos , Brassica napus/fisiologia , Ácidos Graxos/análise , Ácidos Graxos/química , Ácidos Graxos/genética , Flores/efeitos dos fármacos , Flores/genética , Proteínas de Plantas/genética , Plântula/efeitos dos fármacos , Plântula/genética , Sementes/genética , Sequenciamento Completo do Genoma
8.
Cancers (Basel) ; 12(10)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992445

RESUMO

Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of "omics" strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

9.
Elife ; 92020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32844749

RESUMO

Arginine methyltransferase PRMT7 is associated with human breast cancer metastasis. Endosomal FAK signalling is critical for cancer cell migration. Here we identified the pivotal roles of PRMT7 in promoting endosomal FAK signalling activation during breast cancer metastasis. PRMT7 exerted its functions through binding to scaffold protein SHANK2 and catalyzing di-methylation of SHANK2 at R240. SHANK2 R240 methylation exposed ANK domain by disrupting its SPN-ANK domain blockade, promoting in co-accumulation of dynamin2, talin, FAK, cortactin with SHANK2 on endosomes. In addition, SHANK2 R240 methylation activated endosomal FAK/cortactin signals in vitro and in vivo. Consistently, all the levels of PRMT7, methylated SHANK2, FAK Y397 phosphorylation and cortactin Y421 phosphorylation were correlated with aggressive clinical breast cancer tissues. These findings characterize the PRMT7-dependent SHANK2 methylation as a key player in mediating endosomal FAK signals activation, also point to the value of SHANK2 R240 methylation as a target for breast cancer metastasis.


Assuntos
Arginina/metabolismo , Neoplasias da Mama , Quinase 1 de Adesão Focal/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Animais , Arginina/química , Mama/química , Mama/patologia , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Endossomos/metabolismo , Feminino , Humanos , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/química
10.
Zhongguo Gu Shang ; 33(7): 602-8, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32700481

RESUMO

OBJECTIVE: To compare clinical effects of common Kirschner wire, anatomical plate and perforated Kirschner wire in treating olecranon fracture. METHODS: From March 2014 to May 2017, clinical data of 79 patients with olecranon fracture treated with different internal fixation was retrospectively analyzed. Among them, 26 patients treated with common Kirschner wire (group A), including 19 males and 7 females aged from 23 to 51 years old with an average of (37.2±9.6) years old;11 patients were typeⅠ, and 15 patients were typeⅡ according to Mayo classification. Twenty eight patients were treated with olecroanon anatomical plate internal fixation, including 16 males and 12 females aged from 25 to 52 years old with an average of (36.6±8.9) years old;10 patientswere typeⅠ and 18 patients were typeⅡ according to Mayo classification. Twenty five patients were treated with perforated Kirschner wire, including 13 males and 12 females aged from 26 to 51 years old with an average of (38.2±9.2) years old;9 patients were typeⅠand 16 patients were typeⅡ according to Mayo classification. Operation time, intraoperatve blood loss, fracture healing time and postoperative complications among three groups were compared; VAS score at 1 week after operation was used to evaluate pain relief, Broberg-Morrey function score of elbow joint at the final follow up was applied to evaluate clinical effect. RESULTS: Seventy nine patients were followed up from 13 to 23 months with an average of (18.3±4.5) months. Operation time, intraoperatve blood loss, fracture healing time in group A were (82.9±19.7) min, (113.5±32.3) ml, (4.2±0.6) months respectively;in group B were(101.2±24.5) min, (150.2±39.5) ml, (4.6±0.8) months respectively;in group C were (83.3±18.7) min, (119.3±34.3) ml, (4.1±0.5) months respectively. Operation time, intraoperatve blood loss, fracture healing time in group A and group C were better than that of group B(P<0.05). Five patients in group A occurred ineffective internal fixation, other groups did not occurred;9 patients in group A occurred skin irritability, 3 patients in group B and no patient occurred in group C; there were statistical differences in complications among three groups (P<0.05). There were no differences in VAS score at 1 week after operation and Broberg-Morrey function score of elbow joint at the final follow-up among three groups (P>0.05). CONCLUSION: Common Kirschner wire has more complications; anatomical plate has greater surgical trauma and long fracture healing time;while perforated Kirschner wire was not only benefit for fracture union with less trauma, but also could reducing the incidence of postoperative complications, and it is the appropriate method for patients with olecranon fracture.


Assuntos
Olécrano , Fraturas da Ulna , Adulto , Placas Ósseas , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Am J Orthod Dentofacial Orthop ; 157(3): 329-339, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115111

RESUMO

INTRODUCTION: The purpose of this study was to comparatively evaluate the effects of Twin-block (TB) appliance and sagittal-guidance Twin-block (SGTB) appliance on alveolar bone around mandibular incisors in growing patients with Class II Division 1 malocclusion, using cone-beam computed tomography. METHODS: The sample consisted of 25 growing patients with Class II Division 1 malocclusion (14 boys and 11 girls, mean age 11.92 ± 1.62 years) and was randomly distributed into the TB group (n = 13) and the SGTB group (n = 12). The treatment duration was 11.56 ± 1.73 months. Pretreatment (T1) and posttreatment (T2) cone-beam computed tomography scans were taken in both groups. Height, thickness at apex level, and volume of the alveolar bone around mandibular left central incisors were measured respectively on labial and lingual side, using Mimics software (version 19.0; Materialise, Leuven, Belgium). Based on the stable structures, 3-dimensional (3D) registrations of T1 and T2 models were taken to measure the sagittal displacement of incisors. Intragroup comparisons were evaluated by paired-samples t tests and Wilcoxon tests. Independent-samples t tests and Mann-Whitney U tests were used for intergroup comparisons. RESULTS: In both groups, alveolar bone height and volume on the labial side of the incisors significantly decreased after treatment (P <0.05). Lingual alveolar bone height, lingual and total alveolar bone volume, labial, lingual and total alveolar bone thickness showed no significant difference between T1 and T2 (P >0.05). In both groups the incisors tipped labially and drifted to the labial side. Compared with the TB group, less labial alveolar bone loss, less incisor proclination and crown edge drift were found in the SGTB group (P <0.05). CONCLUSIONS: Labial alveolar bone loss around mandibular incisors was observed after both types of appliances treatment in growing patients with Class II Division 1 malocclusion. Less labial alveolar bone loss, less incisor proclination, and crown edge drift were found in the SGTB group than in the TB group during treatment.


Assuntos
Perda do Osso Alveolar , Má Oclusão Classe II de Angle , Aparelhos Ortodônticos , Adolescente , Cefalometria , Criança , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Incisivo , Masculino , Má Oclusão Classe II de Angle/diagnóstico por imagem , Má Oclusão Classe II de Angle/terapia , Mandíbula , Coroa do Dente
13.
Molecules ; 24(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779169

RESUMO

The solid dispersion technique, which is widely used in the medical field, was applied to prepare a pesticide dosage form of emamectin benzoate (EM). The preparation, physicochemical characterization, aqueous solubility, release dynamics, photolytic degradation, bioactivity, and sustained-release effects of the prepared EM solid dispersions were studied by a solvent method, using polymer materials as the carriers. Water-soluble polyvinyl pyrrolidone (PVP) K30 and water-insoluble polyacrylic resin (PR)III were used as the carriers. The influence of various parameters, such as different EM:PVP-K30 and EM:PRIII feed ratios, solvent and container choices, rotational speed and mixing time effects on pesticide loading, and the entrapment rate of the solid dispersions were investigated. The optimal conditions for the preparation of EM-PVP-K30 solid dispersions required the use of methanol and a feed ratio between 1:1 and 1:50, along with a rotational speed and mixing time of 600 rpm and 60 min, respectively. For the preparation of EM-PRIII solid dispersions, the use of methanol and a feed ratio between 1:4 and 1:50 were required, in addition to the use of a porcelain mortar for carrying out the process. Under optimized conditions, the prepared EM-PVP-K30 solid dispersions resembled potato-like, round, and irregular structures with a jagged surface. In contrast, the EM-PRIII solid dispersions were irregular solids with a microporous surface structure. The results of X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), ultraviolet (UV) spectrometry, and infrared (IR) spectrometry showed that the solid dispersions were formed by intermolecular hydrogen bonding. The solid dispersion preparation in PVP-K30 significantly improved the solubility and dissolution rate of EM, particularly the aqueous solubility, which reached a maximum of 37.5-times the EM technical solubility, when the feed ratio of 1:10 was employed to prepare the dispersion. Importantly, the wettable powder of EM-PVP-K30 solid dispersion enhanced the insecticidal activity of EM against the Plutella xylostella larvae. Furthermore, the solid dispersion preparation in PRIII afforded a significant advantage by prolonging the EM technical release in water at a pH below 7.0, especially when the PRIII content in solid dispersions was high. While the amplified toxicity of the wettable powder of EM-PRIII solid dispersions against the P. xylostella larvae showed no significant differences from that of the EM technical, the long-term toxicity under the field condition was much better than that of the commercially available EM 1.5% emulsifiable concentrate. Notably, solid dispersions with both the PVP-K30 and PRIII carriers reduced the effect of UV photolysis.


Assuntos
Preparações de Ação Retardada/química , Ivermectina/análogos & derivados , Tecnologia Farmacêutica/métodos , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Interações Hidrofóbicas e Hidrofílicas , Ivermectina/química , Polímeros/química , Polivinil/química , Pós/química , Pirrolidinas/química , Solubilidade , Solventes/química , Espectrofotometria Infravermelho/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Raios Ultravioleta , Difração de Raios X/métodos
14.
Cancers (Basel) ; 11(9)2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500349

RESUMO

Our recent publications showed that multidrug resistance protein 2 (MRP2, encoded by the ABCC2 gene) conferred oxaliplatin resistance in human liver cancer HepG2 cells. However, the contribution of MRP2 to oxaliplatin resistance remains unclear in colorectal and pancreatic cancer lines. We investigated the effects of silencing MRP2 by siRNA on oxaliplatin accumulation and sensitivity in human colorectal cancer Caco-2 cells and pancreatic cancer PANC-1 cells. We characterized the effects of oxaliplatin on MRP2 ATPase activities using membrane vesicles. Over-expression of MRP2 (endogenously in Caco-2 and PANC-1 cells) was associated with decreased oxaliplatin accumulation and cytotoxicity, but those deficits were reversed by inhibition of MRP2 with myricetin or siRNA knockdown. Silencing MRP2 by siRNA increased oxaliplatin-induced apoptotic rate in Caco-2 and PANC-1 cells. Oxaliplatin stimulated MRP2 ATPase activity with a concentration needed to reach 50% of the maximal stimulation (EC50) value of 8.3 ± 0.7 µM and Hill slope 2.7. In conclusion, oxaliplatin is a substrate of MRP2 with possibly two binding sites, and silencing MRP2 increased oxaliplatin accumulation and cytotoxicity in two widely available gastrointestinal tumour lines (PANC-1 and Caco-2).

15.
Environ Pollut ; 252(Pt B): 1491-1499, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31265960

RESUMO

Understanding the influence of colloids on radionuclide migration is of significance to evaluate environmental risks for radioactive waste disposals. In order to formulate an appropriate modelling framework that can quantify and interpret the anomalous transport of Strontium (Sr) in the absence and presence of colloids, the continuous time random walk (CTRW) approach is implemented in this work using available experimental information. The results show that the transport of Sr and its recovery are enhanced in the presence of colloids. The causes can be largely attributed to the trap-release processes, e.g. electrostatic interactions of Sr, colloids and natural sediments, and differences in pore structures, which gave rise to the varying interstitial velocities of dissolved and, if any, colloid-associated Sr. Good agreement between the CTRW simulations and the column-scale observations is demonstrated. Regardless of the presence of colloids, the CTRW modelling captures the characteristics of non-Fickian anomalous transport (0 < ß < 2) of Sr. In particular, a range of 0 < ß < 1, corresponding to the cases with greater recoveries, reveal strongly non-Fickian transport with distinctive earlier arrivals and tailing effects, likely due to the physicochemical heterogeneities, i.e. the repulsive interactions and/or the macro-pores originating from local heterogeneities. The results imply that colloids can increase the Sr transport as a barrier of Sr sorption onto sediments herein, apart from often being carriers of sored radionuclides in aqueous phase. From a modelling perspective, the findings show that the established CTRW model is valid for quantifying the non-Fickian and promoted transport of Sr with colloids.


Assuntos
Coloides/química , Resíduos Radioativos/análise , Eliminação de Resíduos/métodos , Poluentes Radioativos do Solo/análise , Estrôncio/análise , Poluentes Radioativos da Água/análise , Radioisótopos/análise
16.
Br J Cancer ; 120(7): 728-745, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30816325

RESUMO

BACKGROUND: SHON nuclear expression (SHON-Nuc+) was previously reported to predict clinical outcomes to tamoxifen therapy in ERα+ breast cancer (BC). Herein we determined if SHON expression detected by specific monoclonal antibodies could provide a more accurate prediction and serve as a biomarker for anthracycline-based combination chemotherapy (ACT). METHODS: SHON expression was determined by immunohistochemistry in the Nottingham early-stage-BC cohort (n = 1,650) who, if eligible, received adjuvant tamoxifen; the Nottingham ERα- early-stage-BC (n = 697) patients who received adjuvant ACT; and the Nottingham locally advanced-BC cohort who received pre-operative ACT with/without taxanes (Neo-ACT, n = 120) and if eligible, 5-year adjuvant tamoxifen treatment. Prognostic significance of SHON and its relationship with the clinical outcome of treatments were analysed. RESULTS: As previously reported, SHON-Nuc+ in high risk/ERα+ patients was significantly associated with a 48% death risk reduction after exclusive adjuvant tamoxifen treatment compared with SHON-Nuc- [HR (95% CI) = 0.52 (0.34-0.78), p = 0.002]. Meanwhile, in ERα- patients treated with adjuvant ACT, SHON cytoplasmic expression (SHON-Cyto+) was significantly associated with a 50% death risk reduction compared with SHON-Cyto- [HR (95% CI) = 0.50 (0.34-0.73), p = 0.0003]. Moreover, in patients received Neo-ACT, SHON-Nuc- or SHON-Cyto+ was associated with an increased pathological complete response (pCR) compared with SHON-Nuc+ [21 vs 4%; OR (95% CI) = 5.88 (1.28-27.03), p = 0.012], or SHON-Cyto- [20.5 vs. 4.5%; OR (95% CI) = 5.43 (1.18-25.03), p = 0.017], respectively. After receiving Neo-ACT, patients with SHON-Nuc+ had a significantly lower distant relapse risk compared to those with SHON-Nuc- [HR (95% CI) = 0.41 (0.19-0.87), p = 0.038], whereas SHON-Cyto+ patients had a significantly higher distant relapse risk compared to SHON-Cyto- patients [HR (95% CI) = 4.63 (1.05-20.39), p = 0.043]. Furthermore, multivariate Cox regression analyses revealed that SHON-Cyto+ was independently associated with a higher risk of distant relapse after Neo-ACT and 5-year tamoxifen treatment [HR (95% CI) = 5.08 (1.13-44.52), p = 0.037]. The interaction term between ERα status and SHON-Nuc+ (p = 0.005), and between SHON-Nuc+ and tamoxifen therapy (p = 0.007), were both statistically significant. CONCLUSION: SHON-Nuce+ in tumours predicts response to tamoxifen in ERα+ BC while SHON-Cyto+ predicts response to ACT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Proteínas Oncogênicas/metabolismo , Tamoxifeno/uso terapêutico , Adolescente , Adulto , Idoso , Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Núcleo Celular/metabolismo , Quimioterapia Adjuvante , Intervalo Livre de Doença , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Adulto Jovem
17.
J Biomed Nanotechnol ; 15(1): 204-211, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30480527

RESUMO

Alternative antibody (aptamer)-based biosensors are attracting increasing attention owing to advantages such as simplicity and low cost, which are beneficial for point-of-care diagnosis, particularly where resources are limited. In this study based on in silico modeling predictions made with Autodock Vina, the binding affinity of an optimized novel peptide (Pf_P1: KITTTDEEVEGIFD) was altered compared to that of the original epitope peptide (P1: KITDEEVEGIFDC). The binding energy of Pf_P1 implies that it has stronger interactions with Plasmodium falciparum lactate dehydrogenase (LDH) than with human LDH. Fluorescence-linked immunosorbent assay (FLISA) demonstrated significant interactions (P < 0.05) between the Pf_P1 peptide and P. falciparum LDH at 35.7 nmol. A peptide- and antibody-linked sandwich FLISA was able to detect at least 100 infected red blood cells (RBC)/µL significantly (P < 0.001). The clinical diagnostic performance of peptide- and antibody-linked sandwich FLISA was evaluated using blood samples from patients infected by P. falciparum with parasitemia values of 151 to 128,636. All positive samples exhibited higher fluorescence than normal samples did. In conclusion, in silico modeling was used to efficiently design a Plasmodium LDH epitope-derived peptide aptamer to function as an alternative to antibodies in immunoassays.


Assuntos
Plasmodium falciparum , Aptâmeros de Peptídeos , Humanos , L-Lactato Desidrogenase , Malária Falciparum , Peptídeos
18.
Pharmaceutics ; 10(3)2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30096910

RESUMO

Multidrug resistance (MDR) is a major hurdle which must be overcome to effectively treat cancer. ATP-binding cassette transporters (ABC transporters) play pivotal roles in drug absorption and disposition, and overexpression of ABC transporters has been shown to attenuate cellular/tissue drug accumulation and thus increase MDR across a variety of cancers. Overcoming MDR is one desired approach to improving the survival rate of patients. To date, a number of modulators have been identified which block the function and/or decrease the expression of ABC transporters, thereby restoring the efficacy of a range of anticancer drugs. However, clinical MDR reversal agents have thus far proven ineffective and/or toxic. The need for new, effective, well-tolerated and nontoxic compounds has led to the development of natural compounds and their derivatives to ameliorate MDR. This review evaluates whether synthetically modifying natural compounds is a viable strategy to generate potent, nontoxic, ABC transporter inhibitors which may potentially reverse MDR.

19.
Histopathology ; 73(4): 545-558, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29603357

RESUMO

Endocrine therapy for oestrogen receptor-positive (ER+) breast cancer (BC) is arguably the most successful targeted cancer therapy to date. Nevertheless, resistance to endocrine therapy still occurs in a significant proportion of patients, limiting its clinical utility. ER+ or luminal BC, which represents approximately three-quarters of all breast malignancies, are biologically heterogeneous, with no distinct, clinically defined subclasses able to predict the benefit of endocrine therapy in early settings. To improve patient outcomes there is a clear need for improved understanding of the biology of the luminal BC, with subsequent translation into more effective methods of diagnosis to identify potential predictive biomarkers for endocrine therapy. This review summarises current knowledge of factors predictive of benefit of endocrine therapy and discusses why molecular classification systems of BC have yet to be translated into the clinic.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/classificação , Neoplasias da Mama/tratamento farmacológico , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Humanos , Receptores de Estrogênio/biossíntese
20.
Neoplasia ; 20(1): 99-117, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29245123

RESUMO

The glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs) comprising of GDNF, neurturin, artemin, and persephin plays an important role in the development and maintenance of the central and peripheral nervous system, renal morphogenesis, and spermatogenesis. Here we review our current understanding of GFL biology, and supported by recent progress in the area, we examine their emerging role in endocrine-related and other non-hormone-dependent solid neoplasms. The ability of GFLs to elicit actions that resemble those perturbed in an oncogenic phenotype, alongside mounting evidence of GFL involvement in tumor progression, presents novel opportunities for therapeutic intervention.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Família Multigênica , Neoplasias/etiologia , Neoplasias/metabolismo , Animais , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Humanos , Ligantes , Mutação , Neoplasias/patologia , Neoplasias/terapia , Transdução de Sinais
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