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1.
Food Res Int ; 137: 109688, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233263

RESUMO

In this study, fruit-zone microclimate was modified by three treatments, including inter-row mulch (M), the combination of leaf removal applied at the onset of veraison and inter-row mulch (MLR-BV), and the combination of leaf removal applied at complete veraison and inter-row mulch (MLR-EV), in a semi-arid climate in three consecutive years (2015-2017). M decreased fruit-zone reflected solar radiation from vineyard floor and low temperature (10-20 °C) duration, whereas it increased soil temperature and high temperature (> 30 °C) duration. MLR-BV and MLR-EV increased fruit-zone incident photosynthetically active radiation while decreased the duration of 20-25 °C compared to M. Notably, M significantly decreased grape total norisoprenoid concentrations in 2015-2017, and total terpenoid concentrations in 2015-2016. Applying leaf removal applied at the onset of veraison could compensate the decreases of total norisoprenoids and terpenoids caused by M when two treatments were applied together. Besides, M significantly increased grape total C6/C9 compound concentrations, besides, (Z)-3-hexen-1-ol concentrations were significantly higher in grapes of M than those of MLR-BV in 2015-2017. Light exposure and high temperature duration after veraison had strong positive correlations with total norisoprenoids and terpenoids, besides, low temperature duration was positively correlated with total norisoprenoids. In addition, light exposure after veraison had strong negative correlations with total C6/C9 compounds. With respect to the volatile compounds in wines, M significantly decreased the concentrations of isopentanol and ethyl acetate, and the concentrations of ethyl cinnamate, phenylacetaldehyde, phenylethyl alcohol and 3-methylthio-1-propanol were significantly lower in MLR-BV and MLR-EV than in M. The outcome of this study can assist winegrowers to properly adjust vineyard managements to optimize the concentrations of desired volatile compounds in grapes and wines.

2.
Yi Chuan ; 42(6): 599-612, 2020 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-32694118

RESUMO

Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to personalized precision therapy, due to the individual differences of unique neoantigens. With the discovery of many common oncogenic mutations, and such mutation-associated neoantigens could cover more patients, and hence are valuable in clinical field. However, whether the common neoantigens can be identified in CRC is unknown. Combining the somatic mutations data from 321 CRC patients with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*1101-restricted common neoantigens with a high binding affinity (IC50<50 nmol/L) and presentation score (>0.90). Besides the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens specifically induced in vitro pre- stimulated cytotoxic lymphocyte (CTL) to secrete interferon gamma (IFN-γ). Moreover, combining cell-sorting technology and single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were analyzed and validated. Their related T-cell receptor engineered T cell (TCR-T) cells could also recognize the neoantigens and secrete IFN-γ. Hence, we have established a method to screen for common neoantigens with immunogenicity in CRC based on the public somatic mutation library. It can provide essential peptide and TCR information for immunotherapies, such as peptides, dendritic cells (DC) vaccines, TCR-like antibodies, TCR-T, etc., for the CRC and other cancers, which has practical application value in the clinics.


Assuntos
Antígenos de Neoplasias , Neoplasias Colorretais , Antígenos de Neoplasias/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Detecção Precoce de Câncer , Humanos , Mutação , Receptores de Antígenos de Linfócitos T/genética
3.
New Phytol ; 226(5): 1413-1428, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32119117

RESUMO

Effective legume-rhizobia symbiosis depends on efficient nutrient exchange. Rhizobia need to synthesize iron-containing proteins for symbiotic nitrogen fixation (SNF) in nodules, which depends on host plant-mediated iron uptake into the symbiosome. We functionally investigated a pair of vacuolar iron transporter like (VTL) genes, GmVTL1a/b, in soybean (Glycine max) and evaluated their contributions to SNF, including investigations of gene expression patterns, subcellular localization, and mutant phenotypes. Though both GmVTL1a/b genes were specifically expressed in the fixation zone of the nodule, GmVTL1a was the lone member to be localized at the tonoplast of tobacco protoplasts, and shown to facilitate ferrous iron transport in yeast. GmVTL1a targets the symbiosome in infected cells, as verified by in situ immunostaining. Two vtl1 knockout mutants had lower iron concentrations in nodule cell sap and peribacteroid units than in wild-type plants, suggesting that GmVTL1 knockout inhibited iron import into symbiosomes. Furthermore, GmVTL1 knockout minimally affected soybean growth under nonsymbiotic conditions, but dramatically impaired nodule development and SNF activity under nitrogen-limited and rhizobia-inoculation conditions, which eventually led to growth retardation. Taken together, these results demonstrate that GmVTL1a is indispensable for SNF in nodules as a transporter of ferrous iron from the infected root cell cytosol to the symbiosome.

4.
Onco Targets Ther ; 12: 5499-5513, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371988

RESUMO

Background: ß2-adrenoceptors (ß2-ARs) are expressed on the surface of immune cells, including tumor-associated macrophages (TAMs). Previous studies have demonstrated that the expression of ß2-ARs in hepatocellular carcinoma (HCC) is significantly increased in vitro. However, the role of ß2-AR in M2-polarized macrophages remains unclear. G protein-coupled receptor kinase 2 (GRK2) can regulate G protein-coupled receptor (GPCR). Previous studies showed that down-regulation of GRK2 in HCC contributes the HCC progression, but it still remains unclear whether the regulation of ß2-AR in M2-polarized macrophages by GRK2 can promote HCC. Purpose: The present study was designed to investigate the role of activated ß2-AR in M2-polarized macrophages in the HCC progression and GRK2 regulatory effect, as well as the underlying mechanisms involved. Results: The results demonstrated that the M2-polarized macrophages were increased with HCC progression. In vitro, the activation of ß2-AR by terbutaline in M2-polarized macrophages elevated the proliferative, migratory and invasive attributes of HCC cells. Furthermore, GRK2 down-regulation in ß2-AR activated M2-polarized macrophages activated the downstream cyclic adenosine monophosphate (cAMP)/protein kinase A/cAMP-response element binding protein and cAMP/interleukin-6/signal transducer and the activator of transcription 3 signaling pathways, contributing to the secretion of tumor-associated cytokines, and thus resulting in the promotion of malignant biological behavior in HCC cells. Conclusion: These findings suggest that the regulation of ß2-AR occurs through the silencing of GRK2 in M2-polarized macrophages, which is conducive to HCC development, through its engagement in the activation of downstream signaling.

5.
Cancer Manag Res ; 11: 5425-5435, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354350

RESUMO

Background: Resistance to docetaxel is a major obstacle to effective treatment of breast cancer. Exosomal microRNAs (miRNAs) have recently been introduced in cell-to-cell transmission of chemoresistance between heterogeneous populations of tumor cells with diverse drug sensitivity. However, a systematic evaluation of the exosomal miRNA signature remains largely unclear. Method: miRNA expression profiles in exosomes from docetaxel-resistant (D/exo) and parental sensitive breast cancer cells (S/exo) were assessed using microarray. Bioinformatics analysis was performed to predict target genes of the dysregulated miRNAs and to uncover their potential roles in chemoresistance formation. Signaling pathways, gene ontology terms, transcription factors, protein-protein interactions, and hub genes were also constructed. Results: The selected exosomal miRNAs could modulate target genes responsible for MAPK, TGF-beta, Wnt, mTOR, and PI3K/Akt signaling pathways. Function enrichment analysis revealed the involvement of target genes in transcription regulation, protein phosphorylation, kinase activity, and protein binding. Enriched transcription factors including SP1, SP4, and EGR1 were obtained and a protein-protein interaction network was established. The hub genes for up-expressed and down-expressed exosomal miRNAs such as CCND1 and PTEN were identified. Conclusion: This bioinformatics study provides a comprehensive view of the function of dysregulated exosomal miRNAs, and may help us to understand exosome-mediated resistance transmission and overcome docetaxel resistance in future breast cancer therapy.

6.
Food Chem ; 292: 237-246, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054670

RESUMO

The ripeness of a grape is critical to berry composition and to the resultant wine. For wineries with a single cultivar occupying an extensive area, the total soluble solid of grapes can range from 22°Brix to 28°Brix. Accordingly, the influence of different harvest dates (ripeness) on berry compositions and on the resultant wine profile was investigated for Vitis vinifera L. cv. 'Cabernet Sauvignon.' Berry dehydration was observed as berry weight and juice yields decreased. Berry anthocyanins were concentrated and methylated anthocyanin levels fluctuated with increasing delays in harvesting. Hexanal and 2-hexenal levels in must decreased significantly as berries ripened. In the resultant wines, 2,3-butanediol levels increased. Wines harvested earlier were lighter, presented lower color intensity (CI) values and higher yellow% levels, and exhibited richer aroma profiles (compounds). Through a principal component analysis and discriminant analysis, the compounds characterizing each harvest date were identified.


Assuntos
Vitis/química , Vinho/análise , Aldeídos/análise , Antocianinas/análise , Cromatografia Gasosa , Clima , Frutas/química , Frutas/metabolismo , Análise dos Mínimos Quadrados , Análise de Componente Principal , Fatores de Tempo , Vitis/metabolismo , Compostos Orgânicos Voláteis/análise
7.
Biosci Rep ; 38(6)2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30201690

RESUMO

A major cause of failure in chemotherapy is drug resistance of cancer cells. Exosomes have been introduced to spread chemoresistance through delivering miRNAs. However, a systematic evaluation of the exosomal miRNA expression profiles responsible for chemoresistance is still lacking. In the present study, miRNA signature differentially expressed in exosomes derived from adriamycin-resistant (A/exo) and parental breast cancer cells (S/exo) were analyzed by microarray and the results were confirmed by PCR. A total of 309 miRNAs were increased and 66 miRNAs were decreased significantly in A/exo compared with S/exo. Specifically, 52 novel miRNAs with increased expression levels >16.0-fold in A/exo were identified. After prediction of target genes for 13 of 52 selected novel miRNAs, pathway analysis, gene ontology (GO) terms, and protein-protein interactions (PPIs) were constructed. The results implied that these selected exosomal miRNAs inhibited target genes involved in transcriptional misregulation in cancer, MAPK, and Wnt signaling pathways. Functional enrichment analysis demonstrated that the target genes were mainly responsible for protein phosphorylation, transcription regulation, molecular binding, and kinase activity. In summary, the current bioinformatics study of exosomal miRNAs may offer a new understanding into mechanisms of chemoresistance, which is helpful to find potential exosomal miRNAs to overcome drug insensitivity in future breast cancer treatment.


Assuntos
Neoplasias da Mama/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Doxorrubicina/efeitos adversos , Exossomos/efeitos dos fármacos , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Análise em Microsséries , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , Via de Sinalização Wnt/genética
8.
Biosci Rep ; 38(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30061173

RESUMO

d Rhamnose ß-hederin (DRß-H), an active component extracted from the traditional Chinese medicinal plant Clematis ganpiniana, has been reported to be effective against breast cancer. Recent studies have also indicated that the isolated exosomes (D/exo) from docetaxel-resistant breast cancer cells MCF-7 (MCF-7/Doc) were associated with resistance transmission by delivering genetic cargo. However, the relevance of D/exo during DRß-H exposure remains largely unclear. In the present work, exosomes were characterized by morphology and size distribution. We reinforced the significant role of D/exo in spreading chemoresistance from MCF-7/Doc to recipient sensitive cells after absorption and internalization. DRß-H could reduce the formation and release of D/exo. Next, we demonstrated that DRß-H was able to reverse docetaxel resistance and that D/exo was responsible for DRß-H-mediated resistance reversal. We also found that DRß-H could decrease the expressions of several most abundant miRNAs (miR-16, miR-23a, miR-24, miR-26a, and miR-27a) transported by D/exo. Target gene prediction and pathway analysis showed the involvement of these selected miRNAs in pathways related to treatment failure. Our results suggested that DRß-H could reduce D/exo secretion from MCF-7/Doc cells and induce the reduction in resistance transmission via D/exo.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Docetaxel/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Exossomos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , MicroRNAs/genética , Ácido Oleanólico/farmacologia
9.
Acta Pharmacol Sin ; 39(11): 1699-1705, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29921886

RESUMO

G protein-coupled receptor kinases (GRKs) constitute seven subtypes of serine/threonine protein kinases that specifically recognize and phosphorylate agonist-activated G protein-coupled receptors (GPCRs), thereby terminating the GPCRs-mediated signal transduction pathway. Recent research shows that GRKs also interact with non-GPCRs and participate in signal transduction in non-phosphorylated manner. Besides, GRKs activity can be regulated by multiple factors. Changes in GRKs expression have featured prominently in various tumor pathologies, and they are associated with angiogenesis, proliferation, migration, and invasion of malignant tumors. As a result, GRKs have been intensively studied as potential therapeutic targets. Herein, we review evolving understanding of the function of GRKs, the regulation of GRKs activity and the role of GRKs in human malignant tumor pathophysiology.


Assuntos
Quinases de Receptores Acoplados a Proteína G/metabolismo , Neoplasias/fisiopatologia , Animais , Humanos , Transdução de Sinais/fisiologia
10.
Int J Mol Sci ; 19(5)2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29734668

RESUMO

Among a great variety of cell surface receptors, the largest superfamily is G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors. GPCRs can modulate diverse signal-transduction pathways through G protein-dependent or independent pathways which involve β-arrestins, G protein receptor kinases (GRKs), ion channels, or Src kinases under physiological and pathological conditions. Recent studies have revealed the crucial role of GPCRs in the tumorigenesis and the development of cancer metastasis. We will sum up the functions of GPCRs—particularly those coupled to chemokines, prostaglandin, lysophosphatidic acid, endothelin, catecholamine, and angiotensin—in the proliferation, invasion, metastasis, and angiogenesis of hepatoma cells and the development of hepatocellular carcinoma (HCC) in this review. We also highlight the potential avenues of GPCR-based therapeutics for HCC.


Assuntos
Carcinogênese/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Receptores Acoplados a Proteínas-G/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Metástase Neoplásica , Transdução de Sinais/genética , beta-Arrestinas/genética
11.
Physiol Plant ; 2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29572845

RESUMO

Magnesium (Mg) is an essential element for the growth of both plants and bacteria. Low availability of Mg in agriculture can limit crop productivity and quality. In addition to direct effects on plant growth, limited Mg supply may also impact biological dinitrogen (N2 ) fixation in nodules formed from symbiotic interactions between legumes and rhizobial bacteria. To date, the physiological mechanisms involved in Mg-dependent nodulation remains largely unknown. The objectives of this work were to assess how Mg supply affects nodule growth and development in symbiotic systems, and to test if any observed changes in nodule and soybean are correlated with Mg supply. Here, we found that external Mg supply enhanced nodule growth under nitrogen (N) limited conditions, and subsequently improved N2 fixation and soybean growth. Mg supply altered neither nodule structure nor Mg homeostasis, but remarkably promoted nodule enlargement, resulting in an increase in the number of big nodules. In addition, high Mg supply decreased starch and sucrose accumulation in leaves, and increased their concentrations in roots, which consequently enhanced carbohydrate import into the rhizobia infection zone of nodules. In this study, Mg was shown to promote nodule growth in soybean. This Mg-promoted nodule growth is derived from Mg-facilitated alteration of carbohydrate partitioning and transport into nodules.

12.
Semin Cell Dev Biol ; 74: 142-152, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28822768

RESUMO

Magnesium (Mg) is the second most abundant cation in plants, and, as such, is involved in numerous physiological and biochemical processes, including photosynthesis, enzyme activation, and synthesis of nucleic acids and proteins. Due to its relatively small ionic radius and large hydrated radius, Mg binds weakly to soil and root surfaces, and thereby is easily leached from soil. Mg deficiency not only affects crop productivity and quality, but also contributes to numerous chronic human diseases. Therefore, Mg nutrition in plants is an important issue in nutrition and food security. To acquire and maintain high concentrations of Mg, plants have evolved highly-efficient systems for Mg uptake, storage and translocation. Advances in the understanding of fundamental principles of Mg nutrition and physiology are required in order to improve Mg nutrient management, Mg stress diagnosis, and genetic marker assisted breeding efforts. The aims of this review are to highlight physiological and molecular mechanisms underlying Mg biological functions and to summarize recent developments in the elucidation of Mg transport systems in plants.


Assuntos
Magnésio/metabolismo , Plantas/metabolismo , Transporte Biológico , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
13.
Cancer Res ; 74(13): 3399-407, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24924774

RESUMO

We investigated the loss of somatic mutations in TP53 and PIK3CA in breast cancer tissue after neoadjuvant chemotherapy (NCT) and the clinical relevance of the observed mutation profiles. Samples were derived from three cohorts: Cohort 1 consisting of 206 patients undergoing NCT with matched pre- and postchemotherapy tumor tissues; Cohort 2 consisting of 158 additional patients undergoing NCT; and Cohort 3, consisting of 81 patients undergoing chemotherapy with prechemotherapy tumor tissues. In the first cohort, somatic mutations in TP53 or PIK3CA were identified in 24.8% of the pre-NCT tumor samples but in only 12.1% of the post-NCT tumor samples (P < 0.001). Patients with initial TP53 and PIK3CA mutations who became negative for the mutations after NCT had a higher Miller-Payne score (P = 0.008), improved disease-free survival, and improved overall survival than those with no change or the opposite change. The association of loss of mutations in TP53 and PIK3CA and improved survival was successfully validated in the second cohort. In addition, 28.4% of the tumors showed intratumoral heterogeneity of somatic mutations in TP53 or PIK3CA, whereas 71.6% were homogeneous, either with or without the mutations. Our data reveal the novel concept that chemotherapy may reduce mutation frequency in patients with breast cancer. Furthermore, the loss of somatic mutations in TP53 and PIK3CA may be translated to biomarkers for prognosis via further verification, which may optimize the choice of sequential therapy and improve patient survival.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Terapia Neoadjuvante , Fosfatidilinositol 3-Quinases/genética , Proteína Supressora de Tumor p53/genética , Sequência de Bases , Neoplasias da Mama/mortalidade , Carboplatina/uso terapêutico , Classe I de Fosfatidilinositol 3-Quinases , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Paclitaxel/uso terapêutico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Prostaglandina/metabolismo , Análise de Sequência de DNA
14.
Nat Commun ; 5: 3802, 2014 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-24823476

RESUMO

Among chemotherapeutic agents, paclitaxel has shown great efficacy against breast cancer. Prediction of paclitaxel response may improve patient outcomes. Here we show, using exome sequencing, that in comparison with pre-treatment biopsies, two TEKT4 germline variations are enriched in post-treatment tumours. We find TEKT4 variations in ~ 10% of an independent cohort of 84 pairs of samples. Tektin4 (encoded by TEKT4) associates closely with tubulin in doublet microtubules and helps stabilize these structures. These two TEKT4 germline variations in a high cis linkage are biologically relevant, as the ectopic expression of variant TEKT4 deregulates the microtubule stability, antagonizes the paclitaxel-induced stabilizing effect of microtubules and increases paclitaxel resistance. Furthermore, TEKT4 germline variations are associated with reduced disease-free survival and overall survival compared with wild-type TEKT4 in patients undergoing paclitaxel-based chemotherapy. Taken together, we reveal a potential mechanism of resistance to paclitaxel through the acquisition of germline variations in breast cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas dos Microtúbulos/genética , Microtúbulos/metabolismo , Paclitaxel/uso terapêutico , Adulto , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Variação Genética , Humanos , Pessoa de Meia-Idade , Prognóstico
15.
Ann Surg Oncol ; 21 Suppl 4: S648-56, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24793340

RESUMO

BACKGROUND: Girdin was identified as a novel Akt substrate that contributes to a positive feedback loop between Girdin and Akt. Although several recent studies have demonstrated that Girdin is involved in tumor metastasis, the clinical implications of Girdin in breast cancer remain unclear. METHODS: To retrospectively evaluate the prognostic value of Girdin in breast cancer, we performed an immunohistochemistry screening for Girdin using tissue microarrays constructed from 250 patients who were histologically confirmed as having invasive ductal breast carcinoma at the Fudan University Shanghai Cancer Center. RESULTS: Our results demonstrated that the levels of Girdin in different subcellular distributions, including Girdin in the nucleus (GN) and the cytoplasm (GC) were each associated with the clinical parameters of breast cancer, including phospho-Akt (S473) [p = 0.014 for GN], phospho-Akt (T308) [p = 0.045 for GC], estrogen receptor (ER) [p = 0.012 for GN and p = 0.004 for GC], progesterone receptor (p = 0.028 for GC) and human epidermal growth factor receptor 2 status (p = 0.004 for GC). Moreover, we showed that elevated expression of GN indicated a worse disease-free survival (p = 0.032) and overall survival (p = 0.011) exclusively in the ER-positive breast cancer population. CONCLUSIONS: Cumulatively, our findings suggest that GN might serve as an important prognostic factor for ER-positive breast carcinoma.


Assuntos
Neoplasias da Mama/química , Carcinoma Ductal de Mama/química , Proteínas dos Microfilamentos/análise , Proteínas de Transporte Vesicular/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/química , Citoplasma/química , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Fosforilação , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Estudos Retrospectivos , Taxa de Sobrevida
16.
PLoS One ; 9(1): e86676, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24489766

RESUMO

BACKGROUND: Tumor size is one of the most important factors in making clinical and pathological assessment of breast cancer. In the present study, we aimed to determine whether the preoperative measurement of tumor size, by imaging modalities, deviate from the postoperative pathological measurement in breast cancer. PATIENTS AND METHODS: 1296 patients diagnosed with invasive ductal breast carcinoma (IDC) during 2007 and 2009 were involved. Pre- and postoperative measurements of tumor size were compared using paired t-test and Chi-square test. RESULTS: The mean maximum diameters of tumors by imaging modalities and pathology were 27.9 mm and 22.4 mm, respectively. There was a statistically significant difference of 5.5 mm (95% CI: 4.7-6.2, p<0.001) between them. The discordance between pre- and post-surgical measurements of tumor size had significant effect on choosing surgery type, causing less application of breast conserving therapy (p<0.0001). CONCLUSION: Compared to pathological size, preoperative measurement by imaging modalities tends to overestimate tumor size. These differences could have implications in the treatment of patients with breast cancer.


Assuntos
Mama/patologia , Carcinoma Ductal de Mama/patologia , Adulto , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/mortalidade , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Gradação de Tumores , Período Pré-Operatório , Estudos Retrospectivos , Análise de Sobrevida , Carga Tumoral
17.
Cancer ; 120(9): 1329-37, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24477928

RESUMO

BACKGROUND: The GATA3 gene (GATA-binding protein 3) is one of the most frequently mutated genes in breast cancer. The objective of the current study was to determine the clinicopathologic characteristics of patients with breast cancer harboring GATA3 mutations. METHODS: The authors examined the somatic mutation status of GATA3 and performed survival analysis in The Cancer Genome Atlas (TCGA) cohort (n=934) and the Fudan University Shanghai Cancer Center (FUSCC) cohort (n=308). Patient characteristics, including age; menopausal status; tumor laterality; tumor size; lymph node status; tumor grade; molecular subtypes; adjuvant radiotherapy, chemotherapy, and endocrine therapy; and prognosis, together with PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) and TP53 (tumor protein p53) mutation status, were collected. RESULTS: GATA3 mutations were detected in 8.8% of patients (82 of 934 patients) in the TCGA cohort and 14.9% of patients (46 of 308 patients) in the FUSCC cohort. GATA3 mutations were found to be significantly associated with luminal-like breast cancer (P=.002 in the TCGA cohort and P<.001 in the FUSCC cohort), and were highly mutually exclusive to PIK3CA mutations (P=.001 in the TCGA cohort and P=.003 in the FUSCC cohort) and TP53 mutations (P<.001 in both cohorts). Furthermore, GATA3 mutations were correlated with improved overall survival in the entire population (P=.025 in the TCGA cohort and P = .043 in the FUSCC cohort) as well as in patients with luminal-like disease who received adjuvant endocrine therapy. CONCLUSIONS: GATA3 mutations mainly occur in patients with luminal-like breast cancer and have identifiable clinicopathologic and genetic characteristics, highlighting a subgroup of patients with breast cancer in whom limited therapy may be appropriate.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Fator de Transcrição GATA3/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/classificação , Estudos de Coortes , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Modelos de Riscos Proporcionais , Análise de Sobrevida
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