Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Endocr Relat Cancer ; 27(3): 153-162, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31905165

RESUMO

HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR positive and HR negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR- HER2-positive breast tumors to understand their molecular heterogeneity. In this study, 64 HR+/HER2+ and 43 HR-/HER2+ stage I-III breast cancer patients were included. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76, 61 and 49, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P = 0.004), TGF-beta (P = 0.007) and WNT (P = 0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.

2.
Bioresour Technol ; 291: 121858, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377515

RESUMO

The improved performances during anaerobic degradation of phenol to methane with Fe(OH)3 were usually inapparent, due to its lower solubility (unaccessible to dissimilatory iron reduction) and more positive reduction potential of Fe(III)/Fe(II) (unfavorable for enriching Fe(III)-reducing bacteria [IRBs]). In this study, citrate, the organic chelates, were used to solubilize Fe(III) with the aim of improving the phenol degradation and declining the reduction potential of Fe(III)/Fe(II). Results showed that, in the co-occurrence of citrate and Fe(OH)3, the degradation rates of phenol were about 1.3-fold rapider than that with sole Fe(OH)3. Analysis of cyclic voltammetry demonstrated that the reduction potential of Fe(III)/Fe(II) in the form of Fe(OH)3 (-0.41 to -0.28 V vs Ag/AgCl) declined to -0.61 to -0.41 V. As a result, the Fe(III)-reducing genera, such as Petrimonas and Shewanella, which held a great potential of proceeding syntrophic metabolism via direct interspecies electron transfer (DIET), were significantly enriched.


Assuntos
Quelantes/farmacologia , Compostos Férricos/metabolismo , Ferro/metabolismo , Metano/metabolismo , Fenol/metabolismo , Anaerobiose , Bacteroides/efeitos dos fármacos , Bacteroides/metabolismo , Transporte de Elétrons , Oxirredução , Fenóis/metabolismo , Shewanella/efeitos dos fármacos , Shewanella/metabolismo
3.
Ann Transl Med ; 7(8): 179, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31168460

RESUMO

Background: The complexity of breast cancer at the clinical, morphological and genomic levels has been extensively studied in the western population. However, the mutational genomic profiles in Chinese breast cancer patients have not been explored in any detail. Methods: We performed targeted sequencing using a panel consisting of 33 breast cancer-related genes to investigate the genomic landscape of 304 consecutive treatment-naïve Chinese breast cancer patients at Guangdong Provincial People's Hospital (GDPH), and further compared the results to those in 453 of Caucasian breast cancer patients from The Cancer Genome Atlas (TCGA). Results: The most frequently mutated gene was TP53 (45%), followed by PIK3CA (44%), GATA3 (18%), MAP3K1 (10%), whereas the copy-number amplifications were frequently observed in genes of ERBB2 (24%), MYC (23%), FGFR1 (13%) and CCND1 (10%). Among the 8 most frequently mutated or amplified genes, at least one driver was identifiable in 87.5% (n=267) of our GDPH cohort, revealing the significant contribution of these known driver genes in the development of Chinese breast cancer. Compared to TCGA data, the median age at diagnosis in our cohort was significantly younger (48 vs. 58 years; P<0.001), while the distribution of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) statuses were similar. The largest difference occurred in HR+/HER2- subtype, where 8 of the 10 driver genes compared had statistically significant differences in their frequency, while there were differences in 2 of 10 driver genes among the TNBC and HR+/HER2+ group, but none in the HR-/HER2+ patients in our cohort compared to the TCGA data. Collectively, the most significant genomic difference was a significantly higher prevalence for TP53 and AKT1 in Chinese patients. Additionally, more than half of TP53-mutation HR+/HER2- Chinese patients (~60%) are likely to harbor more severe mutations in TP53, such as nonsense, indels, and splicing mutations. Conclusions: We elucidated the mutational landscape of cancer genes in Chinese breast cancer and further identified significant genomic differences between Asian and Caucasian patients. These results should improve our understanding of pathogenesis and/or metastatic behavior of breast cancer across races/ethnicities, including a better selection of targeted therapies.

4.
Front Psychiatry ; 10: 360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178769

RESUMO

Objectives: Some neurological disorders demonstrate indistinguishable psychological symptoms at an early stage, especially when accompanied by jitters similar to those in Parkinson's disease. During dopamine replacement therapy, some patients display restless leg syndrome (RLS)-like symptoms. Therefore, we aimed to analyze treatment strategies and the prognosis of RLS caused by high-dose Madopar. Methods: Nine patients who were misdiagnosed with Parkinson's disease, taking a high dose of Madopar, and showed symptoms of anxiety, depression, and somatization were recruited. Clinical data were collected, and strategies of treatment and prognosis were analyzed. Results: Seven patients demonstrated varying degrees of anxiety and depression, and the other two cases were misdiagnosed as Parkinson's disease. During Madopar treatment, patients gradually showed aggravated symptoms, including swelling, numbness, pain, and other sensory abnormalities in both lower extremities, which spread to both upper extremities in a few patients. Among the seven patients, symptoms of anxiety, depression, insomnia, and somatization significantly worsened during the observation period. The average time from taking Madopar to the appearance of RLS was 2.6 ± 0.6 months, the average time to clinical diagnosis was 18.17 ± 9.40 months, and the average dosage of Madopar was 1.44 ± 0.21 g per day. Gradually reducing the Madopar dosage and administering a small dose of long-acting dopamine preparation greatly alleviated the symptoms after 3 months. Conclusion: A high dose of Madopar can cause RLS-like symptoms accompanied by anxiety, depression, insomnia, and other mental health symptoms. These symptoms should be more closely monitored by clinicians.

5.
Biomed Pharmacother ; 116: 108997, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31146111

RESUMO

As an important regulator of epigenetics, histone lysine methyltransferase 2C (KMT2C), is frequently mutated in multiple human cancers and is considered to be crucial for the occurrence and development of numerous cancers. However, the relationship between KMT2C mutation and clinicopathological characteristics in patients with breast cancer is unclear. In the present study, we performed next-generation sequencing to investigate the mutation status of KMT2C in 411 treatment-naive Chinese patients with breast cancer at Guangdong Provincial People's Hospital (GDPH), and further compared the results to those of patients with breast cancer from The Cancer Genome Atlas (TCGA, n = 981) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1454) cohorts. The KMT2C mutation rate was 8.0% (33/411) in the GDPH cohort, whereas that in the TCGA and the METABRIC cohorts was 7.0% (69/981) and 14.5% (211/1454), respectively. Nineteen novel mutations were observed in the GDPH cohort. KMT2C mutations were found to be significantly associated with patients older than 50 years (GDPH: p = 0.007; TCGA: p = 0.005; METABRIC: p = 0.015). The KMT2C mutation rate in HR+/HER2- breast cancer patients was higher than that in the other subtypes (GDPH: p = 0.047; TCGA: p = 0.032; METABRIC: p = 0.046). In addition, KMT2C mutations in the GDPH cohort were observed in invasive lobular breast cancer (ILC) at 30.8% (4/13). Further, KMT2C mutation was not found to be an independent risk factor in the prognosis of patients with breast cancer [TCGA: hazard ratio (HR), 1.71; 95% confidence interval (CI), 0.88-3.31; p = 0.111; METABRIC: HR, 2.03; 95% CI, 0.45-3.08; p = 0.419]. This is the first study to preliminarily elucidate the role of KMT2C mutations in Chinese patients with breast cancer and further identified significant KMT2C mutation differences according to race and ethnicity. KMT2C might be a susceptibility gene of Chinese patients with ILC that would help define high-risk groups that could benefit from adapted, personalized screening strategies.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação/genética , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Resultado do Tratamento
6.
ACS Synth Biol ; 8(5): 1134-1143, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-30951293

RESUMO

The regulation of biosynthetic pathways is a universal strategy for industrial strains that overproduce metabolites. Erythromycin produced by Saccharopolyspora erythraea has extensive clinical applications. In this study, promoters of the erythromycin biosynthesis gene cluster were tested by reporter mCherry. The SACE_0720 ( eryBIV)-SACE_0721 ( eryAI) spacer was selected as a target regulatory region, and bidirectional promoters with dual single guide RNAs (sgRNAs) were knocked-in using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 method. qPCR results indicated that knock-in of Pj23119-PkasO, which replaced the native promoter, enabled biosynthetic gene cluster activation, with eryBIV and eryAI expression increased 32 and 79 times, respectively. High performance liquid chromatography results showed that, compared with the wild-type strain, the yield of erythromycin was increased (58.3%) in bidirectional promoter knock-in recombinant strains. On the basis of the activated strain Ab::Pj23119-PkasO, further investigation showed that CRISPR-based interference of sdhA gene affected erythromycin biosynthesis and cell growth. Finally, regulating the culture temperature to optimize the inhibition intensity of sdhA further increased the yield by 15.1%. In summary, this study showed that bidirectional promoter knock-in and CRISPR interference could regulate gene expression in S. erythraea. This strategy has potential application for biosynthetic gene cluster activation and gene regulation in Actinobacteria.

7.
Sci Rep ; 9(1): 1251, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718739

RESUMO

Microcystis, the dominant species among cyanobacterial blooms, normally forms colonies under natural conditions but exists as single cells or paired cells in axenic laboratory cultures after long-term cultivation. Here, a bloom-forming Microcystis aeruginosa strain CHAOHU 1326 was studied because it presents a colonial morphology and grows on the water surface during axenic laboratory culturing. We first examined the morphological features of strain CHAOHU 1326 and three other unicellular M. aeruginosa strains FACHB-925, FACHB-940, and FACHB-975 cultured under the same conditions by scanning and transmission electron microscopy. Then, we compared the extracellular polysaccharide (EPS)-producing ability of colonial strain CHAOHU 1326 to that of the three unicellular M. aeruginosa strains, and found that strain CHAOHU 1326 produced a higher amount of EPS than the other strains during growth. Moreover, based on genome sequencing, multiple gene clusters implicated in EPS biosynthesis and a cluster of 12 genes predicted to be involved in gas vesicle synthesis in strain CHAOHU 1326 were detected. These predicted genes were all functional and expressed in M. aeruginosa CHAOHU 1326 as determined by reverse transcription PCR. These findings provide a physiological and genetic basis to better understand colony formation and buoyancy control during M. aeruginosa blooming.

8.
Chin J Cancer Res ; 30(3): 340-350, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30046228

RESUMO

Objective: Although circulating tumor cells (CTCs) have been well-established as promising prognostic biomarkers in both early breast cancer and metastatic settings, little is known regarding the prognostic relevance of CTCs in the long-term postoperative monitoring of patients with non-metastatic breast cancer (non-MBC). In this study, we investigated the associations of CTCs with clinicopathological features and metabolic-related variables, such as obesity and hyperglycemia. Methods: In this retrospective study, we recruited 264 patients with postoperative stage I-III breast cancer at Guangdong General Hospital from January 2009 to December 2015. The prevalence and number of CTCs were assessed using the CellSearch System at a median time of 19.0 months [interquartile range (IQR), 7.8-33.0] after surgery. The CTC assay results were correlated with the clinicopathological features and metabolic-related variables. A multivariate logistic regression analysis was performed to further determine the independent predictors of CTCs. Results: CTCs were detected in 10.6% of all patients. The positive rate of CTCs in patients with infiltrating ductal carcinoma was lower than that in patients with other pathological types (9.0% vs. 28.6%, P=0.020). More importantly, the presence of CTCs was correlated with blood glucose level (P=0.015) and high-density lipoprotein level (P=0.030). The multivariate logistic regression analysis showed that the pathological type [odds ratio (OR): 1.757, 95% CI: 1.021-3.023; P=0.042] and blood glucose level (OR: 1.218, 95% CI: 1.014-1.465; P=0.035) were independent predictors of the presence of CTCs. Conclusions: This study revealed potential associations between CTCs and metabolic-related factors in Chinese patients with non-MBC and supports the hypothesis that metabolic dysfunction in breast cancer patients might influence the biological activity of metastatic breast cancer, leading to a higher prevalence of CTCs.

9.
Environ Sci Technol ; 52(9): 5339-5348, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29608291

RESUMO

Horizontal transfer of catabolic plasmids is used in genetic bioaugmentation for environmental pollutant remediation. In this study, we examined the effectiveness of genetic bioaugmentation with dioxin-catabolic plasmids harbored by Rhodococcus sp. strain p52 in laboratory-scale sequencing batch reactors (SBRs). During 100 days of operation, bioaugmentation decreased the dibenzofuran content (120 mg L-1) in the synthetic wastewater by 32.6%-100% of that in the nonbioaugmented SBR. Additionally, dibenzofuran was removed to undetectable levels in the bioaugmented SBR, in contrast, 46.8 ± 4.1% of that in the influent remained in the nonbioaugmented SBR after 96 days. Moreover, transconjugants harboring pDF01 and pDF02 were isolated from the bioaugmented SBR after 2 days, and their abilities to degrade dibenzofuran were confirmed. After 80 days, the copy numbers of strain p52 decreased by 3 orders of magnitude and accounted for 0.05 ± 0.01% of the total bacteria, while transconjugants were present at around 106 copies mL-1 sludge and accounted for 8.2 ± 0.3% of the total bacteria. Evaluation of the bacterial community profile of sludge by high-throughput 16S rRNA gene sequencing revealed that genetic bioaugmentation led to a bacterial community with an even distribution of genera in the SBR. This study demonstrates the promise of genetic bioaugmentation with catabolic plasmids for dioxins remediation.


Assuntos
Dioxinas , Rhodococcus , Reatores Biológicos , Plasmídeos , RNA Ribossômico 16S , Esgotos
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 34(7): 1016-9, 1024, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25057075

RESUMO

OBJECTIVE: To study the incidence of implantation metastasis of breast cancer in vacuum-assisted breast biopsy (VABB) needle tract in Chinese patients and evaluate the effect of neoadjuvant chemotherapy on needle tract metastasis following VABB. METHODS: The breast cancer patients with established diagnosis by VABB were divided into two groups to receive open surgery or neoadjuvant chemotherapy prior to open surgery. The incidence of needle tract metastasis, disease-free survival (DFS) and overall survival (OS) were compared between the two groups. RESULTS: A total of 214 patients were enrolled, among whom 94 directly underwent surgeries and 120 had neoadjuvant chemotherapy before surgery. The two groups showed no significant differences in the incidence of needle tract metastasis (3.2% vs 0.8%, P=0.206), DFS (P=0.221), or OS (P=0.531). CONCLUSION: The incidence of needle tract metastasis is low after VABB, and neoadjuvant chemotherapy does not increase this risk.


Assuntos
Biópsia por Agulha/métodos , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Segunda Neoplasia Primária/tratamento farmacológico , Mama , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Agulhas , Vácuo
11.
Clin Transl Oncol ; 15(1): 79-84, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22926944

RESUMO

INTRODUCTION: The timing of sentinel lymph node biopsy (SLNB) of breast cancer in the neoadjuvant setting is still controversial. We retrospectively analyzed a Chinese patient cohort with neoadjuvant chemotherapy (NAC) to evaluate the accuracy and axilla sparing potentials of different SLNB timings with methylene blue alone for lymphatic mapping. MATERIALS AND METHODS: Patients with NAC and axillary lymph node dissection (ALND) and either pre- or post-NAC SLNB were eligible. Clinicopathological characteristics, identification rate (IR), false-negative rate (FNR), accuracy, and positive-predictive value were calculated and compared between the pre- and post-NAC SLNB group using appropriate statistical methods. Axilla sparing potentials of different SLNB timings were evaluated and compared. RESULTS: One hundred and fifteen eligible cases were included, and 58 had pre-NAC SLNB while the other 57 had post-NAC SLNB. Both groups were comparable in clinicopathological characteristics, neoadjuvant treatments and pathologic complete response rate. IR, FNR, and accuracy of SLNB, as pre-NAC versus post-NAC, were 100 versus 98.2 % (P = 0.496), 0 versus 8.0 % (P = 0.181), and 100 versus 96.4 % (P = 0.239), respectively. Post-NAC SLNB had significantly higher positive-predictive value for ALNs than pre-NAC SLNB (70.0 vs. 36.4 %, P = 0.014), suggesting as high as 63.6 % of ALND performed in the pre-NAC group could have been avoided while only 30 % of ALND in the post-NAC group were theoretically unnecessary. CONCLUSIONS: Both SLNB timings of breast cancer patients with NAC were feasible and accurate. Although pre-NAC SLNB tends to be better in accuracy, post-NAC SLNB is significantly superior in terms of axilla sparing.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Linfonodos/cirurgia , Azul de Metileno/química , Adulto , Neoplasias da Mama/patologia , Corantes , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Biópsia de Linfonodo Sentinela/métodos
12.
Med Oncol ; 29(5): 3222-31, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22547076

RESUMO

Trastuzumab-containing neoadjuvant chemotherapy achieves a pathologic complete response (pCR) rate of about 40 % in HER2-positive breast cancers, and pCR predicts better survival. A cohort of 102 consecutive Chinese HER2-positive stage II/III patients with neoadjuvant trastuzumab/taxanes were retrospectively analyzed, to evaluate the role of hormonal receptor (HR) status and Ki67 index, along with other parameters, in pCR and survival prediction. pCR rate of the cohort was 44.1 % (45/102). Fifty-three patients were HR-positive and 49 were HR-negative. Median Ki67 index was 40 %, and 49 patients had a high Ki67 index (>40 %) whereas 53 had a low Ki67 index (≤40 %). HR status and Ki67 index were confirmed as the only two parameters associated with pCR in multivariate analysis (hazard ratio = 2.952; 95 % CI, 1.227-7.105; P = 0.016 for HR status and hazard ratio = 2.583, 95 % CI 1.107-6.026, P = 0.028 for Ki67 index). Patients with coexisting HR-negative and high Ki67 index had higher pCR rate (69.2 %), compared to those with either HR-negative alone or high Ki67 alone (hazard ratio = 3.038; 95 % CI, 1.102-8.372; P = 0.029), and to those with coexisting HR-positive and low Ki67 index as well (hazard ratio = 7.071; 95 % CI, 2.150-23.253; P = 0.001). In a median follow-up duration of 25.9 months, 11 disease-free survival events (DFS) were recorded. pCR predicted better DFS (log rank P = 0.018) and was the only significant factor in Cox regression analysis (hazard ratio = 0.184; 95 % CI, 0.038-0.893; P = 0.036). Our study indicates that HR status and Ki67 index are predictors for pCR but not for DFS in HER2-positive patients with neoadjuvant trastuzumab/taxanes, which deserves further investigations.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Esteroides/metabolismo , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/genética , Receptores de Esteroides/genética , Trastuzumab , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA