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1.
Front Plant Sci ; 15: 1374925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606078

RESUMO

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.

2.
J Appl Clin Med Phys ; : e14279, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38259194

RESUMO

BACKGROUND: Local recurrence in locally advanced pancreatic cancer (LAPC) after carbon-ion radiotherapy (CIRT) may partly attribute to low dose-averaged linear energy transfer (LETd ), despite high CIRT dose. PURPOSE: This study aimed to investigate the approaches to up-modulate the CIRT LETd and to evaluate the corresponding oxygen enhancement ratio (OER) reduction. METHODS: 10 LAPCs that had been irradiated by CIRT with 67.5 Gy (RBE) in 15 fractions were selected. Their original plans were taken as the control plan for the LETd and OER investigations. Our considerations for up-modulating LETd were: (1) to deliver high doses to gross tumor volume core (GTVcore), while keeping dose constraints of the gastrointestinal (GI) tract in tolerance; (2) to put more Bragg-peak (BP) within the modulated targets; (3) to increase the BP density, high doses were necessary; (4) CIRT LETd could be effectively increased to small volumes; and (5) simultaneous integrated boost technique (SIB) could achieve the aforementioned tasks. The LETd and the corresponding OER distributions of each type of SIB plan were evaluated. RESULTS: We delivered up to 100 Gy (RBE) to GTVcore using SIB. The mean LETd of GTV increased significantly by 21.3% from 47.8 to 58.0 keV/µm (p < 0.05). Meanwhile, the mean OER of GTVcore decreased by 6.6%, from 1.51 to 1.41 (p < 0.05). The GI LETd S in all modulated plans were not more than those in the original plans. CONCLUSIONS: SIB could effectively increase CIRT LETd to LAPC, thus producing reduced OER, which may effectively overcome the radioresistance of LAPCs.

4.
Int J Mol Sci ; 24(4)2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36834578

RESUMO

Seed sugar composition, mainly including fructose, glucose, sucrose, raffinose, and stachyose, is an important indicator of soybean [Glycine max (L.) Merr.] seed quality. However, research on soybean sugar composition is limited. To better understand the genetic architecture underlying the sugar composition in soybean seeds, we conducted a genome-wide association study (GWAS) using a population of 323 soybean germplasm accessions which were grown and evaluated under three different environments. A total of 31,245 single-nucleotide polymorphisms (SNPs) with minor allele frequencies (MAFs) ≥ 5% and missing data ≤ 10% were selected and used in the GWAS. The analysis identified 72 quantitative trait loci (QTLs) associated with individual sugars and 14 with total sugar. Ten candidate genes within the 100 Kb flanking regions of the lead SNPs across six chromosomes were significantly associated with sugar contents. According to GO and KEGG classification, eight genes were involved in the sugar metabolism in soybean and showed similar functions in Arabidopsis. The other two, located in known QTL regions associated with sugar composition, may play a role in sugar metabolism in soybean. This study advances our understanding of the genetic basis of soybean sugar composition and facilitates the identification of genes controlling this trait. The identified candidate genes will help improve seed sugar composition in soybean.


Assuntos
Glycine max , Locos de Características Quantitativas , Glycine max/genética , Desequilíbrio de Ligação , Estudo de Associação Genômica Ampla , Açúcares/metabolismo , Sementes/metabolismo , Polimorfismo de Nucleotídeo Único
5.
Int Immunopharmacol ; 113(Pt A): 109263, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36334370

RESUMO

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms. METHODS: We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs). RESULTS: MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes. CONCLUSION: Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.


Assuntos
Piperazinas , Piridonas , Animais , Camundongos , Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Piridonas/farmacologia , Piperazinas/farmacologia
6.
Strahlenther Onkol ; 198(4): 361-369, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34618172

RESUMO

PURPOSE: To identify the indications for hepatocellular carcinoma (HCC) irradiated by intensity-modulated photon radiotherapy (IMRT), proton radiotherapy (PRT) or carbon-ion radiotherapy (CIRT) by comparing of dosimetric parameters and incidences of classic radiation-induced liver disease (RILD). METHODS: In all, 40 HCCs were divided into group A (tumors located > 1 cm away from gastrointestinal [GI] tract), and group B (tumors located < 1 cm away from GI tract). The prescribed curative doses were 60 Gy (relative biological effectiveness [RBE]) in 10 fractions for group A, and 67.5 Gy (RBE) in 15 fractions for group B. IMRT, PRT and CIRT plans were separately generated to reach the curative doses and coverage. Dosimetric parameters evaluated were mean dose to normal liver (MDTNL) and the volume of normal liver receiving more than 1 Gy (RBE) (V1). Lyman-Kutcher-Burman model was used to determine the incidences of classic RILD, and Power model of non-linear regression, to estimate the tumor volume that could be irradiated with the curative doses within dose constraint of MDTNL. RESULTS: With comparable target doses, the MDTNL (Gy [RBE]) were 18.8 ± 3.7, 13.5 ± 3.1 and 12.8 ± 2.7 in group A and 24.9 ± 7.1, 18.2 ± 3.7 and 17.5 ± 3.7 in group B, respectively, for IMRT, PRT and CIRT. The classic RILD incidences (%) were 22.3 ± 30.0 in IMRT, 2.3 ± 4.9 in PRT and 1.2 ± 2.4 in CIRT. V1 (%) were 89.9 ± 8.8, 43.0 ± 10.2 and 45.9 ± 8.8, respectively, for IMRT, PRT and CIRT. CONCLUSIONS: PRT and CIRT could spare the liver more than IMRT. IMRT could deliver the curative doses to HCC up to a diameter of 7.9 cm; PRT, up to 13.2 cm; and CIRT, up to 14.8 cm.


Assuntos
Carcinoma Hepatocelular , Radioterapia com Íons Pesados , Neoplasias Hepáticas , Radioterapia de Intensidade Modulada , Carcinoma Hepatocelular/radioterapia , Humanos , Neoplasias Hepáticas/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos
7.
Front Oncol ; 11: 766822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858845

RESUMO

OBJECTIVES: This study aimed to investigate the tolerance and effect of proton plus carbon-ion radiotherapy with concurrent chemotherapy in limited-stage small cell lung cancer using the pencil beam scanning technique. MATERIALS AND METHODS: From March 2017 to April 2020, 25 patients with limited-stage small cell lung cancer treated with combined proton and carbon-ion radiotherapy were analyzed. The primary lesions and involved lymph nodes were irradiated using 2-4 portals. Proton and sequential carbon-ion beams were delivered with a median dose of 67.1 (range, 63-74.8) GyE as fraction doses of 2.0-2.2 GyE with proton beams in 20-23 fractions and 3.0-3.8 GyE with carbon ions in 5-8 fractions. Chemotherapy was delivered concurrently with radiotherapy in all patients. RESULTS: At the last follow-up, the 2-year overall and locoregional progression-free survival rates were 81.7% and 66.7%, respectively. Radiochemotherapy was well tolerated, with grade 1, 2, and 3 acute toxicities occurring in 12.0%, 68.0%, and 20.0% of patients, respectively. All grade 3 acute toxicities were hematologically related changes. One patient experienced grade 3 acute non-hematological toxicity in the esophagus, and one other patient had grade 3 bronchial obstruction accompanied by obstructive atelectasis as a late side effect. CONCLUSION: Proton plus carbon-ion radiotherapy using pencil beam scanning yielded promising survival rates and tolerability in patients with limited-stage small cell lung cancer. A prospective clinical study is warranted to validate the therapeutic efficacy of particle radiotherapy in combination with chemotherapy in limited-stage small cell lung cancer.

8.
BMC Cancer ; 21(1): 734, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174854

RESUMO

BACKGROUND: Tracheobronchial adenoid cystic carcinoma (TACC) is a rare tumour. About one-third of patients miss their chance of surgery or complete resection as it is mostly detected in the advanced stage; hence, photon radiotherapy (RT) is used. However, the outcomes of photon RT remain unsatisfactory. Carbon ion radiotherapy (CIRT) is thought to improve the therapeutic gain ratio; however, the outcomes of CIRT in TACC are unclear. Therefore, we aimed to assess the effects and toxicities of CIRT in patients with TACC. METHODS: The inclusion criteria were as follows: 1) age 18-80 years; 2) Eastern Cooperative Oncology Group Performance Status 0-2; 3) histologically confirmed TACC; 4) stage III-IV disease; 5) visible primary tumour; and 6) no previous RT history. The planned prescription doses of CIRT were 66-72.6 GyE/22-23 fractions. The rates of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Treatment-induced toxicities and tumour response were scored according to the Common Terminology Criteria for Adverse Events and Response Evaluation Criteria in Solid Tumors, respectively. RESULTS: Eighteen patients with a median age of 48 (range 30-73) years were enrolled. The median follow-up time was 20.7 (range 5.8-44.1) months. The overall response rate was 88.2%. Five patients developed lung metastasis after 12.2-41.0 months and one of them experienced local recurrence at 31.9 months after CIRT. The rates of 2-year OS, LC, and PFS were 100, 100, and 61.4%, respectively. Except for one patient who experienced grade 4 tracheal stenosis, which was relieved after stent implantation, no other ≥3 grade toxicities were observed. CONCLUSIONS: CIRT might be safe and effective in the management of TACC based on a short observation period. Further studies with more cases and longer observation are warranted.


Assuntos
Neoplasias Brônquicas/radioterapia , Carcinoma Adenoide Cístico/radioterapia , Traqueíte/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Radioterapia com Íons Pesados/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
9.
Radiat Oncol ; 16(1): 72, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849589

RESUMO

BACKGROUND: The study objective was to establish the local effect model (LEM) rectum constraints for 12-, 8-, and 4-fraction carbon-ion radiotherapy (CIRT) in patients with localized prostate carcinoma (PCA) using microdosimetric kinetic model (MKM)-defined and LEM-defined constraints for 16-fraction CIRT. METHODS: We analyzed 40 patients with PCA who received 16- or 12-fraction CIRT at our center. Linear-quadratic (LQ) and RBE-conversion models were employed to convert the constraints into various fractionations and biophysical models. Based on them, the MKM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to 12-, 8-, and 4-fraction CIRT using the LQ model. Then, MKM constraints were converted to LEM using the RBE-conversion model. Meanwhile the LEM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to LEM using the RBE-conversion model. Then, LEM constraints were converted from 16-fraction constraints to the rectum constraints for 12-, 8-, and 4-fraction CIRT using the LQ model. The LEM constraints for 16- and 12-fraction CIRT were evaluated using rectum doses and clinical follow-up. To adapt them for the MKM LQ strategy, CNAO LEM constraints were first converted to MKM constraints using the RBE-conversion model. RESULTS: The NIRS (i.e. DMKM|v, V-20%, 10%, 5%, and 0%) and CNAO rectum constraints (i.e. DLEM|v, V-10 cc, 5 cc, and 1 cc) were converted for 12-fraction CIRT using the MKM LQ strategy to LEM 37.60, 49.74, 55.27, and 58.01 Gy (RBE), and 45.97, 51.70, and 55.97 Gy (RBE), and using the LEM LQ strategy to 39.55, 53.08, 58.91, and 61.73 Gy (RBE), and 49.14, 55.30, and 59.69 Gy (RBE). We also established LEM constraints for 8- and 4-fraction CIRT. The 10-patient RBE-conversion model was comparable to 30-patient model. Eight patients who received 16-fraction CIRT exceeded the corresponding rectum constraints; the others were within the constraints. After a median follow-up of 10.8 months (7.1-20.8), No ≥ G1 late rectum toxicities were observed. CONCLUSIONS: The LEM rectum constraints from the MKM LQ strategy were more conservative and might serve as the reference for hypofractionated CIRT. However, Long-term follow-up plus additional patients is necessary.


Assuntos
Carcinoma/radioterapia , Fracionamento da Dose de Radiação , Radioterapia com Íons Pesados/métodos , Neoplasias da Próstata/radioterapia , Reto/anatomia & histologia , Humanos , Cinética , Masculino , Análise de Componente Principal , Próstata/efeitos da radiação , Radiometria , Radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica Relativa
10.
Brain Res Bull ; 171: 183-195, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33745949

RESUMO

Inflammation plays a pivotal role in promoting the pathophysiology of ischemic stroke (IS). Microglia is the major immunocompetent cells involved in different neuropathologies. The activation of cyclic GMP-AMP synthase (cGAS) and its downstream signaling protein-stimulator of interferon genes (STING) is increasingly recognized as a crucial determinant of neuropathophysiology. However, the mechanisms underlying cGAS-STING signaling regulating inflammatory response during IS remains to be elucidated. In this study, HT22 cells was used to establish an oxygen-glucose deprivation (OGD) cell model in vitro, and then this cell culture supernatant containing OGD-induced DAMPs (OIDs) was employed to stimulate BV2 microglia. Furthermore, a middle cerebral artery occlusion (MCAO) mouse model was established. Cells and MCAO mice were treated with si-cGAS or si-NC lentivirus. The expression levels of STING, cGAS and p-IRF3 in BV2 cells or MCAO mouse brain; the microglial M1/M2 polarization of BV2 microglia or isolated microglial cells from MCAO mouse brain; the contents of iNOS, TNF-α, TGF-ß and IL-10 in the culture medium of BV2 cells or in murine brain homogenates, were all detected. In addition, the severity of cerebral infarction with or without the knockdown of cGAS in a MCAO mouse model was also determined by TTC staining. Results showed that OGD-induced DAMPs strongly activated cGAS-STING pathway and triggered microglia polarization in BV2 cells, reflecting as the accumulation of a plethora of pro-inflammatory factors in activated microglia. However, these effects could be inhibited by cGAS knockdown. In the MCAO mouse model, the inhibition of cGAS-STING pathway resulted from cGAS knockdown could effectively diminish cell apoptosis in mouse brain stimulated by MIDs (MCAO-induced DAMPs), reduced the area ratio of cerebral infarction and ultimately improved the injured nerve function during IS. Taken together, our elucidation of underlying mechanisms involved in the microglial inflammatory response, triggered by cGAS-STING signaling, highlights this pathway as a potential therapeutic target in IS.


Assuntos
Polaridade Celular/genética , AVC Isquêmico/patologia , Proteínas de Membrana/metabolismo , Microglia/patologia , Nucleotidiltransferases/metabolismo , Transdução de Sinais/fisiologia , Animais , Linhagem Celular , Técnicas de Silenciamento de Genes , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , Proteínas de Membrana/genética , Camundongos , Microglia/metabolismo , Doenças Neuroinflamatórias/genética , Doenças Neuroinflamatórias/metabolismo , Nucleotidiltransferases/genética
11.
J Sci Food Agric ; 101(4): 1515-1522, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32851665

RESUMO

BACKGROUND: Edamame is a vegetable soybean (Glycine max) rich in protein with well-balanced amino acid profiles, including all the essential amino acids. It is also relatively high in oil consisting of five fatty acids. In this study, fatty and amino acid contents in oven-dried edamame and mature seeds in 54 genotypes were analyzed to help edamame breeding and relevant research. RESULTS: Significant differences (P < 0.01) between dried edamame and mature soybeans were found for all traits, suggesting that the contents of seed fatty and amino acids varied with drying method and/or growth stage. The genotypic effects were significant for amino acids in all cases and mostly for fatty acids. Fatty acid content was more variable than amino acids in both edamame and mature soybeans. The broad-sense heritability estimates of traits in mature soybeans (51.89-90.37%) were larger than those in edamame seeds (13.10-81.83%), and the estimates for amino acids were larger than those for fatty acids. Correlations between the two edamame drying methods or between the edamame and mature soybeans were significant for all fatty and amino acids with few exceptions, and the correlation coefficients for amino acids (0.36-0.89) were larger than those for fatty acids (0.29-0.81). CONCLUSIONS: Selection for both fatty and amino acids in edamame seems less effective than that in mature soybeans, and the improvement of amino acids would be more achievable than fatty acid improvement. Indirect selection through mature soybeans may benefit the edamame improvement for most of the amino acids. © 2020 Society of Chemical Industry.


Assuntos
Aminoácidos/química , Ácidos Graxos/química , Glycine max/química , Dessecação , Manipulação de Alimentos , Genótipo , Sementes/química , Sementes/classificação , Sementes/genética , Sementes/crescimento & desenvolvimento , Glycine max/genética , Glycine max/crescimento & desenvolvimento
12.
Radiat Oncol ; 15(1): 101, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381042

RESUMO

OBJECTIVE: To identify a safe carbon ion radiotherapy (CIRT) regimen for patients with locally advanced pancreatic cancer (LAPC). METHODS: We generated treatment plans for 13 consecutive, unselected patients who were treated for LAPC with CIRT at our center using three dose and fractionation schedules: 4.6 GyRBE × 12, 4.0 GyRBE × 14, and 3.0 GyRBE × 17. We tested the ability to meet published dose constraints for the duodenum, stomach, and small bowel as a function of dose schedule and distance between the tumor and organs at risk. RESULTS: Using 4.6 GyRBE × 12 and 4.0 GyRBE × 14, critical (high-dose) constraints could only reliably be achieved when target volumes were not immediately adjacent to organs at risk. Critical constraints could be met in all cases using 3.0 GyRBE × 17. Low-dose constraints could not uniformly be achieved using any dose schedule. CONCLUSION: While selected patients with LAPC may be treated safely with a CIRT regimen of 4.6 GyRBE × 12, our dosimetric analyses indicate that a more conservative schedule of 3.0 GyRBE × 17 may be required to safely treat a broader population of LAPC patients, including those with large tumors and tumors that approach gastrointestinal organs at risk. The result of this work was used to guide an ongoing clinical trial.


Assuntos
Fracionamento da Dose de Radiação , Radioterapia com Íons Pesados/métodos , Neoplasias Pancreáticas/radioterapia , Radiometria , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco
13.
J Sci Food Agric ; 100(10): 3987-3994, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32337733

RESUMO

BACKGROUND: Edamame, a vegetable soybean (Glycine max) grown mainly in Asia, has high nutritional and market value and is a relatively new crop to North America. By 2 years of field trials, we evaluated the seed composition traits in 54 genotypes to analyze the differences and relationship between edamame seeds dried by two oven-drying methods and mature soybeans. RESULTS: The genotypic differences were significant for all the traits investigated. Significant differences also existed between the two sets of dried edamame and mature seeds. Protein content in mature soybean averaged 426.8 g kg-1 , and 432.8 g kg-1 and 405.6 g kg-1 for shelled-dried and unshelled-dried edamame respectively. Oil content in shelled-dried and unshelled-dried edamame averaged 206.3 g kg-1 and 212.6 g kg-1 respectively, and 195.8 g kg-1 for mature soybean. Sucrose content in mature soybean (60.2 g kg-1 ) was approximately 1.5 and 3 times that of unshelled-dried and shelled-dried edamame respectively. Mature soybean also exhibited the highest concentrations of stachyose and total sugars, followed by unshelled-dried and shelled-dried edamame. The broad-sense heritability estimates of traits in mature soybean (49.41-89.16%) were higher than those of edamame (10.26-78.96%). Higher broad-sense heritability was uncovered for protein and oil, but lower estimates for sugars, fiber, and ash. Positive correlations were detected between the two sets of edamame seeds and mature soybean for protein and oil (r = 0.63-0.88). CONCLUSION: The results suggest that indirect selection through mature seeds is helpful for the improvement of protein and oil in edamame, whereas the improvement of seed sugars in edamame is more challenging. © 2020 Society of Chemical Industry.


Assuntos
Manipulação de Alimentos/métodos , Glycine max/química , Óleos de Plantas/análise , Proteínas de Soja/análise , Açúcares/análise , Genótipo , Sementes/química
14.
Int J Radiat Oncol Biol Phys ; 107(1): 98-105, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987968

RESUMO

PURPOSE: This prospective phase 2 study evaluated the efficacy and safety of intensity modulated radiation therapy plus etoposide/cisplatin (EP) for patients with unresectable thymic epithelial tumors (TETs). METHODS AND MATERIALS: Patients with limited advanced unresectable TETs whose lesions could be encompassed within radiation fields were enrolled in this study. Two cycles of EP (75 mg/m2 etoposide and 25 mg/m2 cisplatin on days 1-3 and days 29-31) were administered concurrently with radiation therapy, followed by 2 cycles after radiation therapy. The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival rate, overall survival rate, and incidence of adverse events. RESULTS: Fifty-six patients were enrolled between June 2011 and May 2018. Twenty-two and 34 patients had thymomas and thymic carcinomas, respectively. The median age was 52 (range, 21-76) years, and 30 patients (53.6%) were men. Eight patients (14.3%) had stage III tumors, 6 (10.7%) had stage IVA tumors, and 42 (75.0%) had stage IVB tumors. The objective response rate was 85.7% (95% confidence interval, 76.3%-95.2%). With a median follow-up of 46 (range, 7-101) months, the 1-, 2-, and 5-year progression-free survival rates were 66.1%, 48.0%, and 29.5%, and the 1-, 2-, and 5-year overall survival rates were 91.0%, 76.2%, and 56.2%, respectively. The most common grade 3 to 4 adverse event was leukopenia (42.9%). Pulmonary fibrosis was also observed (5.3%). CONCLUSIONS: Because intensity modulated radiation therapy with EP is effective and safe for limited advanced unresectable TETs, it could be a suitable treatment option for such patients.


Assuntos
Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/radioterapia , Radioterapia de Intensidade Modulada , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/radioterapia , Adulto , Idoso , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Segurança , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia , Resultado do Tratamento , Adulto Jovem
15.
Thorac Cancer ; 10(3): 519-525, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30648821

RESUMO

BACKGROUND: Concurrent chemoradiation is the standard treatment for locally advanced esophageal squamous cell carcinoma (SCC). We conducted a phase II study to explore the effect of three-dimensional conformal radiotherapy (3-DCRT) alone for patients with locally advanced esophageal SCC. This study aimed to analyze the long-term survival outcomes. METHODS: Between November 2004 and April 2007, 30 patients with thoracic esophageal SCC underwent late-course sequential boost 3-DCRT at Fudan University Shanghai Cancer Center. The planning target volume (PTV1) comprised a 1.2-1.5 cm lateral margin around the gross tumor volume and a 3.0 cm margin, superior and inferior to the gross tumor volume. PTV2 encompassed the gross tumor volume with a margin of 0.5-0.7 cm. The PTV1 dose delivered was 50 Gy, and the PTV2 dose was a boost dose of 16 Gy, resulting in a total dose of 66 Gy. No chemotherapy was administered. RESULTS: The median follow-up time was 30 months for all patients, and 132 months for patients who were alive. The median overall survival was 27 months (95% confidence interval [CI] 18.9-35.0). The 2-, 5-, and 10-year overall survival rates were 56.6%, 33.3%, and 26.6%, respectively. The median progression-free survival was 14 months (95% CI 7.7-20.2 months), and the 2-, 5-, and 10-year progression-free survival rates were 33.3%, 30.0%, and 26.6%, respectively. No severe late toxicity was observed in long-term survivors. CONCLUSION: Late-course sequential boost 3-DCRT is safe and feasible with promising long-term outcomes for esophageal SCC.


Assuntos
Carcinoma de Células Escamosas do Esôfago/epidemiologia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Radioterapia Conformacional , Idoso , China , Terapia Combinada , Fracionamento da Dose de Radiação , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Planejamento da Radioterapia Assistida por Computador , Taxa de Sobrevida , Resultado do Tratamento
16.
Plant Genome ; 11(3)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30512046

RESUMO

Soybean aphid [ Matsumura (Hemiptera: Aphididae)] is the most damaging insect pest of soybean [ (L.) Merr.] in the Upper Midwest of the United States and is primarily controlled by insecticides. Soybean aphid resistance (i.e., genes) has been documented in some soybean accessions but more sources of resistance are needed. Incorporation of the resistance into marketed varieties has also been slow. Genome-wide association mapping can aid in identifying resistant accessions by correlating phenotypic data with single nucleotide polymorphisms (SNPs) across a genome. Aphid population measures from 2366 soybean accessions were collected from published studies screening cultivated soybean () and wild soybean ( Siebold & Zucc.) with aphids exhibiting Biotype 1, 2, or 3 characteristics. Genotypic data were obtained from the SoySNP50K high-density genotyping array previously used to genotype the USDA Soybean Germplasm Collection. Significant associations between SNPs and soybean aphid counts were found on 18 of the 20 soybean chromosomes. Significant SNPs were found on chromosomes 7, 8, 13, and 16 with known genes. SNPs were also significant on chromosomes 1, 2, 4 to 6, 9 to 12, 14, and 17 to 20 where genes have not yet been mapped, suggesting that many genes remain to be discovered. These SNPs can be used to determine accessions that are likely to have novel aphid resistance traits of value for breeding programs.


Assuntos
Resistência à Doença/genética , Glycine max/genética , Doenças das Plantas/genética , Animais , Afídeos , Genes de Plantas , Estudo de Associação Genômica Ampla , Doenças das Plantas/parasitologia , Polimorfismo de Nucleotídeo Único , Glycine max/parasitologia
17.
Mol Plant ; 11(3): 460-472, 2018 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-29305230

RESUMO

The complex genetic architecture of quality traits has hindered efforts to modify seed nutrients in soybean. Genome-wide association studies were conducted for seed composition, including protein, oil, fatty acids, and amino acids, using 313 diverse soybean germplasm accessions genotyped with a high-density SNP array. A total of 87 chromosomal regions were identified to be associated with seed composition, explaining 8%-89% of genetic variances. The candidate genes GmSAT1, AK-HSDH, SACPD-C, and FAD3A of known function, and putative MtN21 nodulin, FATB, and steroid-5-α-reductase involved in N2 fixation, amino acid biosynthesis, and fatty acid metabolism were found at the major-effect loci. Further analysis of additional germplasm accessions indicated that these major-effect loci had been subjected to domestication or modern breeding selection, and the allelic variants and distributions were relevant to geographic regions. We also revealed that amino acid concentrations related to seed weight and to total protein had a different genetic basis. This helps uncover the in-depth genetic mechanism of the intricate relationships among the seed compounds. Thus, our study not only provides valuable genes and markers for soybean nutrient improvement, both quantitatively and qualitatively, but also offers insights into the alteration of soybean quality during domestication and breeding.


Assuntos
Glycine max/genética , Glycine max/fisiologia , Melhoramento Vegetal , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Glycine max/metabolismo
18.
BMC Plant Biol ; 17(1): 91, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28558691

RESUMO

BACKGROUND: Achieving appropriate maturity in a target environment is essential to maximizing crop yield potential. In soybean [Glycine max (L.) Merr.], the time to maturity is largely dependent on developmental response to dark periods. Once the critical photoperiod is reached, flowering is initiated and reproductive development proceeds. Therefore, soybean adaptation has been attributed to genetic changes and natural or artificial selection to optimize plant development in specific, narrow latitudinal ranges. In North America, these regions have been classified into twelve maturity groups (MG), with lower MG being shorter season than higher MG. Growing soybean lines not adapted to a particular environment typically results in poor growth and significant yield reductions. The objective of this study was to develop a molecular model for soybean maturity based on the alleles underlying the major maturity loci: E1, E2, and E3. RESULTS: We determined the allelic variation and diversity of the E maturity genes in a large collection of soybean landraces, North American ancestors, Chinese cultivars, North American cultivars or expired Plant Variety Protection lines, and private-company lines. The E gene status of accessions in the USDA Soybean Germplasm Collection with SoySNP50K Beadchip data was also predicted. We determined the E allelic combinations needed to adapt soybean to different MGs in the United States (US) and discovered a strong signal of selection for E genotypes released in North America, particularly the US and Canada. CONCLUSIONS: The E gene maturity model proposed will enable plant breeders to more effectively transfer traits into different MGs and increase the overall efficiency of soybean breeding in the US and Canada. The powerful yet simple selection strategy for increasing soybean breeding efficiency can be used alone or to directly enhance genomic prediction/selection schemes. The results also revealed previously unrecognized aspects of artificial selection in soybean imposed by soybean breeders based on geography that highlights the need for plant breeding that is optimized for specific environments.


Assuntos
Glycine max/crescimento & desenvolvimento , Modelos Genéticos , Genes de Plantas , Banco de Sementes , Seleção Genética
19.
World J Gastroenterol ; 23(3): 540-546, 2017 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-28210091

RESUMO

AIM: To evaluate the long-term effectiveness and late toxicities of paclitaxel (PTX) plus cisplatin (DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer. METHODS: Between 2008 and 2011, 76 patients were enrolled in a phase II study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy (68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP (25 mg/m2 per day for 3 d) and PTX (175 mg/m2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern. RESULTS: A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient (heart failure). In log-rank analysis, the pretreatment stage (stage II + III: 36.1 mo vs stage IV: 14.9 mo) and the completed cycle (1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors (P = 0.037 < 0.05 and P = 0.013 < 0.05). CONCLUSION: Radiotherapy combined with chemotherapy consisting of PTX and DDP is a safe and effective definitive treatment for loco-regionally advanced esophageal squamous cancer.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida , Resultado do Tratamento
20.
Front Plant Sci ; 7: 445, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27148284

RESUMO

Abiotic stresses, including high soil salinity, significantly reduce crop production worldwide. Salt tolerance in plants is a complex trait and is regulated by multiple mechanisms. Understanding the mechanisms and dissecting the components on their regulatory pathways will provide new insights, leading to novel strategies for the improvement of salt tolerance in agricultural and economic crops of importance. Here we report that soybean salt tolerance 1, named GmST1, exhibited strong tolerance to salt stress in the Arabidopsis transgenic lines. The GmST1-overexpressed Arabidopsis also increased sensitivity to ABA and decreased production of reactive oxygen species under salt stress. In addition, GmST1 significantly improved drought tolerance in Arabidopsis transgenic lines. GmST1 belongs to a 3-prime part of Glyma.03g171600 gene in the current version of soybean genome sequence annotation. However, comparative reverse transcription-polymerase chain reaction analysis around Glyma.03g171600 genomic region confirmed that GmST1 might serve as an intact gene in soybean leaf tissues. Unlike Glyma.03g171600 which was not expressed in leaves, GmST1 was strongly induced by salt treatment in the leaf tissues. By promoter analysis, a TATA box was detected to be positioned close to GmST1 start codon and a putative ABRE and a DRE cis-acting elements were identified at about 1 kb upstream of GmST1 gene. The data also indicated that GmST1-transgenic lines survived under drought stress and showed a significantly lower water loss than non-transgenic lines. In summary, our results suggest that overexpression of GmST1 significantly improves Arabidopsis tolerance to both salt and drought stresses and the gene may be a potential candidate for genetic engineering of salt- and drought-tolerant crops.

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