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1.
Org Lett ; 22(1): 98-101, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31829608

RESUMO

The recently discovered antibiotic burnettramic acid A (1) and three new congeners, burnettramic acids C-E (2-4), were identified from the co-cultures of two marine Aspergillus strains. The structure of burnettramic acid A was revised on the basis of reinterpretation of the nuclear magnetic resonance (NMR) data and chemical derivatization. The full absolute configurations of burnettramic acids were established using the Mosher ester method and Marfey's analysis, combined with density functional theory calculation of NMR and electric circular dichroism data.

2.
Front Aging Neurosci ; 11: 190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402860

RESUMO

The globus pallidus occupies a critical position in the indirect pathway of the basal ganglia motor control system. Hyperpolarization-activated cyclic-nucleotide gated (HCN) channels play an important role in the modulation of neuronal excitability. In vivo extracellular single unit recording, behavioral test and immunohistochemistry were performed to explore the possible modulation of endogenous HCN channels in the globus pallidus under parkinsonian states. In MPTP parkinsonian mice, micro-pressure application of the selective HCN channel antagonist, ZD7288, decreased the firing rate in 10 out of the 28 pallidal neurons, while increased the firing rate in another 15 out of the 28 neurons. In 6-OHDA parkinsonian rats, ZD7288 also bidirectionally regulated the spontaneous firing activity of the globus pallidus neurons. The proportion of pallidal neurons with ZD7288-induced slowing of firing rate tended to reduce in both parkinsonian animals. Morphological studies revealed a weaker staining of HCN channels in the globus pallidus under parkinsonian state. Finally, behavioral study demonstrated that intrapallidal microinjection of ZD7288 alleviated locomotor deficits in MPTP parkinsonian mice. These results suggest that endogenous HCN channels modulate the activities of pallidal neurons under parkinsonian states.

3.
Molecules ; 24(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382398

RESUMO

A new pyrazine derivative, trypilepyrazinol (1), a new α-pyrone polyketide, (+)-neocitreoviridin (2), and a new ergostane analogue, 3ß-hydroxyergosta-8,14,24(28)-trien-7-one (3), were isolated and characterized along with five known compounds from the marine-derived fungus Penicillium sp. IMB17-046. The structures of these new compounds were determined using spectroscopic data analyses (HRESIMS, 1D- and 2D-NMR), X-ray crystallography analysis, and TDDFT ECD calculation. Compounds 1 and 3 exhibited broad-spectrum antiviral activities against different types of viruses, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza A virus (IAV), with IC50 values ranging from 0.5 to 7.7 µM. Compounds 1 and 2 showed antibacterial activities against Helicobacter pylori, a causative pathogen of various gastric diseases, with minimum inhibitory concentration (MIC) values of 1-16 µg/mL.


Assuntos
Antivirais/farmacologia , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Penicillium/química , Antivirais/química , Produtos Biológicos/química , Linhagem Celular , HIV/efeitos dos fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
4.
J Integr Plant Biol ; 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31180179

RESUMO

High amylose starch can be produced by plants deficient in the function of branching enzymes (BEs). Here we report the production of transgenic cassava (Manihot esculenta Crantz) with starches containing up to 50% amylose due to the constitutive expression of hair-pin dsRNAs targeting the BE1 or BE2 genes. All BE1-RNAi plant lines (BE1i) and BE2-RNAi plant lines (BE2i) were grown up in the field, but with reduced total biomass production. Considerably high amylose content in the storage roots of BE2i plant lines was achieved. Storage starch granules of BE1i and BE2i plants had similar morphology as wild type (WT), however, the size of BE1i starch granules were bigger than that of WT. Comparisons of amylograms and thermograms of all three sources of storage starches revealed dramatic changes to the pasting properties and a higher melting temperature for BE2i starches. Glucan chain length distribution analysis showed a slight increase in chains of DP>36 in BE1i lines and a dramatic increase in glucan chains between DP 10-20 and DP>40 in BE2i lines. Furthermore, BE2i starches displayed a B-type X-ray diffraction pattern instead of the A-type pattern found in BE1i and WT starches. Therefore, cassava BE1 and BE2 function differently in storage root starch biosynthesis.

5.
J Nat Prod ; 82(5): 1391-1395, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31013089

RESUMO

Raistrickindole A (1), a new indole diketopiperazine alkaloid containing an unusual pyrazino[1',2':2,3][1,2]oxazino[6,5- b]indole tetraheterocyclic ring system, a new benzodiazepine derivative, raistrickin (2), and the known haenamindole (3) and sclerotigenin (4) were isolated from the marine-derived fungus Penicillium raistrickii IMB17-034. Their structures were elucidated by extensive spectroscopic analyses and TDDFT calculations of the NMR and ECD data. Compounds 1 and 2 showed inhibitory activities against the hepatitis C virus.

6.
Prostate ; 79(7): 709-719, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30825345

RESUMO

OBJECTIVES: The predictive value of the histological parameters and molecular markers for neoadjuvant hormonal therapy (NHT) in prostate cancer (PCa) has not been well established. The aim of this study is to determine pathological variables that can predict differences in response to NHT in PCa. METHODS: A total of 85 locally high risk PCa patients with matched preoperative needle biopsies and radical prostatectomy (RP) specimens were included. All patients were treated with NHT for at least 3 months. We quantified the response to NHT using a new proposed pathological grading system. The system classified tumors into five groups (grades 0-4) according to the severity of histological response. We then categorized the PCa patients into drug-sensitive (DS) group (Grades 2-4) and drug-resistant (DR) group (Grades 0-1). Two pathologists assessed each pretreated tumors for presence or absence of nine morphological features. The expression of androgen receptor (AR), ERG, and PTEN were evaluated by immunohistochemistry (IHC) as well. Statistical analysis was performed to identify significant associations between differentially histological response to NHT and morphological features as well as molecular aberrations. We evaluated different prediction models using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) analysis. RESULTS: 73% (n = 62/85) of tumors in our cohort belonged to DS group, whereas 27% (n = 23/85) of tumors were DR. Univariate logistic analysis suggested four pathological variables, cribriform growth pattern, macronucleoli, ductal adenocarcinoma differentiation, and PTEN loss in needle biopsies were significantly associated with DR effect, all with P-value < 0.05. Multivariate logistic regression analysis revealed that the three parameters as significant predictive factors for predicting DR effect. These were macronucleoli (RR = 4.008, P = 0.002), ductal adenocarcinoma differentiation (RR = 11.659, P = 0.009) and PTEN loss expression (RR = 7.275, P = 0.015). The AUC of three integrated indicators model was 0.781. CONCLUSIONS: Our study suggested that the presence of tumor cribriform growth pattern, macronucleoli, ductal adenocarcinoma differentiation, and PTEN loss in needle biopsies are of value in predicting tumor response to NHT regimen. Multivariate logistic regression analysis revealed the performance of combined pathological indicators in predicting DR response was better than that of model based on individual factor alone.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/administração & dosagem , Terapia Neoadjuvante/métodos , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/classificação , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Antagonistas de Androgênios , Biópsia por Agulha , Resistencia a Medicamentos Antineoplásicos/fisiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/biossíntese , Valor Preditivo dos Testes , Prognóstico , Prostatectomia , Neoplasias da Próstata/classificação , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/biossíntese , Regulador Transcricional ERG/biossíntese
7.
Mar Drugs ; 16(10)2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30241346

RESUMO

Six new tetracenomycin congeners, saccharothrixones E⁻I (1⁻5) and 13-de-O-methyltetracenomycin X (6), were isolated from the rare marine-derived actinomycete Saccharothrix sp. 10-10. Their structures were elucidated by spectroscopic analysis and time-dependent density functional theory (TDDFT)-electronic circular dichroism (ECD) calculations. Saccharothrixones G (3) and H (4) are the first examples of tetracenomycins featuring a novel ring-A-cleaved chromophore. Saccharothrixone I (5) was determined to be a seco-tetracenomycin derivative with ring-B cleavage. The new structural characteristics, highlighted by different oxidations at C-5 and cleavages in rings A and B, enrich the structural diversity of tetracenomycins and provide evidence for tetracenomycin biosynthesis. Analysis of the structure⁻activity relationship of these compounds confirmed the importance of the planarity of the naphthacenequinone chromophore and the methylation of the polar carboxy groups for tetracenomycin cytotoxicity.


Assuntos
Actinomycetales/química , Antineoplásicos/farmacologia , Organismos Aquáticos/química , Naftacenos/farmacologia , Policetídeos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Dicroísmo Circular , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Naftacenos/química , Naftacenos/isolamento & purificação , Policetídeos/química , Quinonas/química , Relação Estrutura-Atividade
8.
J Nat Prod ; 81(1): 178-187, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29308897

RESUMO

Analysis of the whole genome sequence of Streptomyces sp. IMB7-145 revealed the presence of seven type I polyketide synthase biosynthetic gene clusters, one of which was highly homologous to the biosynthetic gene cluster of azalomycin F. Detailed bioinformatic analysis of the modular organization of the PKS gene suggested that this gene is responsible for niphimycin biosynthesis. Guided by genomic analysis, a large-scale cultivation ultimately led to the discovery and characterization of four new niphimycin congeners, namely, niphimycins C-E (1-3) and 17-O-methylniphimycin (4). The configurations of most stereocenters of niphimycins have not been determined to date. In the present study, the relative configurations were elucidated by spectroscopic analysis, including J-based analysis and the CNMR database method. Further, the full absolute configurations of niphimycins were completely proposed for the first time based on biosynthetic gene cluster analysis of the ketoreductase and enoylreductase domains for hydroxy- and methyl-bearing stereocenters. Compounds 1, 3, 4, and niphimycin Iα (5) showed antimicrobial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (MIC: 8-64 µg/mL), as well as cytotoxicity against the human HeLa cancer cell line (IC50: 3.0-9.0 µM). In addition, compounds 1 and 5 displayed significant activity against several Mycobacterium tuberculosis clinical isolates (MIC: 4-32 µg/mL).


Assuntos
Organismos Aquáticos/química , Streptomyces/química , Streptomyces/genética , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Genômica/métodos , Guanidinas/química , Guanidinas/farmacologia , Células HeLa , Células Hep G2 , Humanos , Células K562 , Células MCF-7 , Macrolídeos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Família Multigênica/genética , Policetídeo Sintases/genética
9.
Zhonghua Zhong Liu Za Zhi ; 37(5): 379-82, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26463031

RESUMO

OBJECTIVE: The aim of this study was to analyze the efficacy and safety of paclitaxel liposomal and docetaxel for neoadjuvant chemotherapy of breast cancer. METHODS: We retrospectively analyzed the clinical data of 188 operable patients with breast cancer who received neoadjuvant chemotherapy. According to the treatment regimens, they were divided into the group of paclitaxel liposome (86 patients) and group of docetaxel (102 patients) treatment. All the patients received a combination therapy with epirubicin and cyclophosphamide, i.e. neoadjuvant chemotherapy with three drugs, 21 days as a cycle, and a total of 6 cycles. Surgery was carried out three weeks after the end of chemotherapy, and the chemotherapy efficacy and adverse reaction of both groups were evaluated. RESULTS: Pathological complete response (pCR) rate in the paclitaxel liposome group and docetaxel group was 10.5% and 9.8%, respectively, the objective response rate (ORR) was 80.2% and 79.4%, respectively, and the disease control rate (DCR) was 95.3% and 93.1%, respectively, showing a non-significant difference in therapy efficacy between the two groups (P > 0.05). Safety analysis indicated that all the occurrence rates of skin and nail toxic reaction, body fluid retention, oral mucositis, allergic reaction (such as facial blushing, chest distress, palpitation, dyspnea. etc.), and grade III-IV leukopenia and neutropenia in the paclitaxel liposome group were significantly lower than that of the docetaxel group (all P < 0.05). CONCLUSIONS: Compared with docetaxel, paclitaxel liposome has the same anti-tumor efficacy, but causes fewer and milder adverse reactions with a higher safety in the neoadjuvant chemotherapy for breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Ciclofosfamida/uso terapêutico , Docetaxel , Epirubicina/uso terapêutico , Feminino , Humanos , Lipossomos , Neutropenia , Paclitaxel/uso terapêutico , Indução de Remissão , Taxoides/uso terapêutico
10.
Mol Cell Neurosci ; 68: 46-55, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25858108

RESUMO

The globus pallidus plays a significant role in motor control under both health and pathological states. Recent studies have revealed that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels occupy a critical position in globus pallidus pacemaking activity. Morphological studies have shown the expression of HCN channels in the globus pallidus. To investigate the in vivo effects of HCN channels in the globus pallidus, extracellular recordings and behavioral tests were performed in the present study. In normal rats, micro-pressure ejection of 0.05mM ZD7288, the selective HCN channel blocker, decreased the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The average decrease was 50.4±5.4%. Interestingly, in another 18 out of the 40 pallidal neurons, ZD7288 increased the firing rate by 137.1±27.6%. Similar bidirectional modulation on the firing rate was observed by a higher concentration of ZD7288 (0.5mM) as well as another HCN channel blocker, CsCl. Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by 63.0±9.3% in 15 out of the 25 pallidal neurons and decreased the firing rate by 46.9±9.4% in another 8 out of the 25 pallidal neurons. Further experiments revealed that modulation of glutamatergic but not GABAergic transmission may be involved in ZD7288-induced increase in firing rate. Consistent with electrophysiological results, further studies revealed that modulation of HCN channels also had bidirectional effects on behavior. Taken together, the present studies suggest that HCN channels may modulate the activity of pallidal neurons by different pathways in vivo.


Assuntos
Globo Pálido/citologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Neurônios/fisiologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Cardiotônicos/farmacologia , Césio/farmacologia , Cloretos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Postura/fisiologia , Pirimidinas/farmacologia , Ratos , Ratos Wistar , Núcleo Subtalâmico/lesões , Valina/análogos & derivados , Valina/farmacologia , Vigília
11.
Zhonghua Yi Xue Za Zhi ; 94(36): 2808-11, 2014 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-25534096

RESUMO

OBJECTIVE: To explore the prognosis of occult breast cancer. METHODS: From January 1978 to December 2008, retrospective analyses were conducted for 205 female patients with axillary lymph node metastasis from an unknown primary source. RESULTS: During a median follow-up time of 61 (4-158) months, the 5 and 10-year rates of disease-free survival (DFS) were 63.5% and 39.8% respectively. The median overall survival (OS) was 10 years. And the 5 and 10-year OS were 79.8% and 49.4% respectively. Significant differences existed in medical history, family history, estrogen receptor (ER), human epidermal growth factor receptor-2 (HER-2), infiltration of soft tissue, surgical option, neoadjuvant chemotherapy, chemotherapy, and radiotherapy with DFS of occult breast cancer (P < 0.05). The most important determinants of DFS and OS were ER, infiltration of soft tissue and neoadjuvant chemotherapy (P < 0.05). CONCLUSION: Radical mastectomy should be performed instead of modified radical mastectomy to improve the patient quality of life.


Assuntos
Neoplasias da Mama , Diagnóstico Diferencial , Qualidade de Vida , Axila , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfonodos , Metástase Linfática , Mastectomia Radical Modificada , Terapia Neoadjuvante , Prognóstico , Receptor ErbB-2 , Receptores Estrogênicos , Estudos Retrospectivos
12.
Cell Cycle ; 13(8): 1299-305, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24621502

RESUMO

Breast cancer is a disease of cell cycle, and the dysfunction of cell cycle checkpoints plays a vital role in the occurrence and development of breast cancer. We employed multi-gene fluorescence in situ hybridization (M-FISH) to investigate gene copy number aberrations (CNAs) of 4 genes (Rb1, CHEK2, c-Myc, CCND1) that are involved in the regulation of cell cycle, in order to analyze the impact of gene aberrations on prognosis in the young breast cancer patients. Gene copy number aberrations of these 4 genes were more frequently observed in young breast cancer patients when compared with the older group. Further, these CNAs were more frequently seen in Luminal B type, Her2 overexpression, and tiple-negative breast cancer (TNBC) type in young breast cancer patients. The variations of CCND1, Rb1, and CHEK2 were significantly correlated with poor survival in the young breast cancer patient group, while the amplification of c-Myc was not obviously correlated with poor survival in young breast cancer patients. Thus, gene copy number aberrations (CNAs) of cell cycle-regulated genes can serve as an important tool for prognosis in young breast cancer patients.


Assuntos
Neoplasias da Mama/genética , Dosagem de Genes , Genes cdc , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/patologia , Quinase do Ponto de Checagem 2/genética , Ciclina D1/genética , Feminino , Genes myc , Humanos , Hibridização in Situ Fluorescente/métodos , Prognóstico , Receptor ErbB-2/genética , Proteína do Retinoblastoma/genética
13.
Zhonghua Zhong Liu Za Zhi ; 36(9): 671-6, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25564057

RESUMO

OBJECTIVE: This study was conducted to analyze the Ki-67 expression before and after neoadjuvant chemotherapy and clinicopathological characteristics of different biological breast cancer phenotypes. The significance and prognostic predictive value of the changes of Ki-67 expression in different biological breast cancer phenotypes were analyzed. METHODS: A regression analysis was performed on 178 patients with invasive breast carcinoma who accepted neoadjuvant chemotherapy at Tianjin Medical University Cancer Institute and Hospital from August 2007 to August 2008. These patients were subtyped by hormone receptor status and HER-2 status. The Ki-67 index (percentage of Ki-67-positive cancer cell nuclei) was determined by immunohistochemistry. The prognostic value of Ki-67 index for disease-free survival (DFS) in different biological breast cancer phenotypes was analyzed using Kaplan-Meier survival and multivariable Cox regression. RESULTS: The overall pathologic CR (pCR) rate, defined as no invasive residuals in the breast and axilla, was 15.2%. The highest pCR rate of 25.0% was observed in the TNBC patients, which was 14.3%, 10.3% and 18.2% in the luminal A, luminal B and HER2 overexpressing patients, respectively (P = 0.040). The changes of Ki-67 expression in pre-NAC and post-NAC patients showed a prognostic significance in luminal A and TNBC (P = 0.019 and P = 0.022, respectively) cases. Clinical stage, the efficacy of NAC, and changes of Ki-67 expression between pre- and post-NAC were independent prognostic factors in TNBC patients who did not achieve pCR. CONCLUSIONS: The Ki-67 expression after neoadjuvant chemotherapy is an independent prognostic factor affecting the disease-free survival (DFS) in TNBC patients who have not achieved pCR.


Assuntos
Neoplasias da Mama/metabolismo , Antígeno Ki-67/metabolismo , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Fenótipo , Prognóstico , Receptor ErbB-2 , Receptores Estrogênicos , Receptores de Progesterona
14.
Tumour Biol ; 35(3): 2035-45, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24096546

RESUMO

This study selected luminal-type breast cancer patients as the study subjects. The patients were divided into groups according to the presence of diabetes and the types of medication used, and the patients' clinicopathological characteristics and prognostic indicators were explored. A total of 5,785 patients with luminal-type breast cancer admitted to Tianjin Medical University Cancer Institute and Hospital between January 2002 and December 2006 were selected as the study subjects. The subjects included 680 breast cancer patients with diabetes and 5,105 breast cancer patients without diabetes. The patients were divided into Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes. Each subtype was further divided into a metformin group, a non-metformin group, and a nondiabetic group. The research indicators included breast cancer mortality, age, body mass index (BMI), amenorrhea, the presence of cardiovascular and cerebrovascular disease, pathological stage, pathological type, lymph node involvement, vessel carcinoma embolus, and the chemotherapy and endocrine regimen. A Kaplan-Meier analysis was conducted to analyze the differences in breast cancer mortality rates among the groups. The Cox proportional hazard model was adopted to detect independent factors related to prognosis. Kaplan-Meier univariate analysis showed that for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes, the cancer-specific mortality rates differed significantly among the metformin, non-metformin, and nondiabetic groups. The 5-year survival rates were 94%, 82%, and 91% (P = 0.002); 93.5%, 81%, and 89% (P < 0.001); and 84%, 77%, and 83% (P = 0.035) for the subtypes within each group, respectively. Cox regression multivariate analysis showed that compared with the metformin group, all three subtypes of the, the non-metformin group showed poorer prognosis (hazard ratio [HR], 3.579; 95% confidence interval [CI], 1.506-8.506 [P = 0.004]; HR, 3.232; 95% CI, 1.839-5.678 [P < 0.001]; HR, 2.034; 95% CI,1.019-4.059 [P = 0.044] for Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+, respectively). Compared with the metformin group, the diabetic group showed poorer prognosis only for the Luminal B (high ki67) subtype (HR, 1.762; 95% CI, 1.033-3.005 [P = 0.038]). In addition, for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subgroups, there was a higher proportion of elderly patients (P < 0.001) and postmenopausal patients (P < 0.001) in the metformin and non-metformin groups than in the nondiabetic group. Moreover, the probability of having cardiovascular and cerebrovascular disease was also higher (P < 0.001) in the metformin and non-metformin groups. For the Luminal B (high ki67) and Luminal B (her-2/neu +) subgroups, there was a higher proportion of obese patients in the metformin and non-metformin groups (P < 0.001). In terms of clinical characteristics, for the Luminal B (high ki67) subtype, the proportion of patients with invasive ductal carcinoma was lower in the non-metformin group than in the other two groups (P = 0.001). In both the metformin and non-metformin groups, the proportion of T3/4 patients was higher (P < 0.001), the proportion of patients with lymph node metastasis was higher (P = 0.001), and the proportion of patients with vessel carcinoma embolus was higher (P = 0.001) compared with the nondiabetic group. In conclusion, compared with the metformin group, the non-metformin group had a poorer prognosis for all subtypes of luminal breast cancer. In the diabetic group, only patients with the Luminal B (high ki67) subtype exhibited a poorer prognosis. Therefore, different diabetes medication may have a different impact on the prognosis of different subtypes of luminal breast cancer.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Adulto , Idoso , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Estimativa de Kaplan-Meier , Metformina/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais
15.
Neurosci Bull ; 29(6): 701-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23839052

RESUMO

The globus pallidus in rodents, equivalent to the external segment of the globus pallidus in primates, plays an important role in movement regulation. Previous studies have shown abundant γ-aminobutyric acid (GABA)ergic innervation and GABAA receptors in the globus pallidus. In this study, we investigated the effects of endogenous GABAA receptors on the spontaneous firing activity of pallidal neurons in both normal and MPTP-treated mice using multi-barrel electrodes extracellular recordings in vivo. We found that in normal mice, pressure ejection of 0.1 mmol/L gabazine, a specific GABAA receptor antagonist, increased the spontaneous firing rate of globus pallidus neurons by 27.6 ± 5.6%. Furthermore, in MPTP mice (14 days after MPTP treatment), 0.1 mmol/L gabazine increased the firing rates by 51.0 ± 7.9%, significantly greater than in normal mice. These results suggest that endogenous GABAA receptors modulate the activity of globus pallidus neurons. The present findings may provide a rationale for investigations into the potential role of GABAA receptors in Parkinson's disease.


Assuntos
Globo Pálido/fisiopatologia , Intoxicação por MPTP/fisiopatologia , Neurônios/fisiologia , Receptores de GABA-A/fisiologia , Potenciais de Ação/fisiologia , Animais , Antagonistas GABAérgicos/farmacologia , Globo Pálido/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Piridazinas/farmacologia
16.
Zhonghua Zhong Liu Za Zhi ; 35(2): 135-9, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23714670

RESUMO

OBJECTIVE: To evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy. METHODS: A total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed. RESULTS: Brain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05). CONCLUSIONS: Cardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Epirubicina/uso terapêutico , Razoxano/uso terapêutico , Adolescente , Adulto , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Medula Óssea/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/cirurgia , Fármacos Cardiovasculares/efeitos adversos , Quimioterapia Adjuvante , Epirubicina/efeitos adversos , Feminino , Seguimentos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Neutrófilos/citologia , Razoxano/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Adulto Jovem
17.
Chin J Cancer Res ; 25(1): 46-54, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23372341

RESUMO

The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis. miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT), whereas let-7b, miR-381, miR-10b, miR-125a-5p, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR (RT-PCR), we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and 10 healthy people. miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients (P<0.05). By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis. miR-205 was down-regulated and miR-155 was up-regulated in BC patient serum. miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status.

18.
Breast Cancer Res Treat ; 137(3): 807-16, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23292119

RESUMO

The purpose of this study was to investigate the clinical, pathological, and prognostic characteristics of breast cancer patients with diabetes. In total, the study included 1,013 breast cancer patients with diabetes and 4,621 breast cancer patients without diabetes. Patients with diabetes were further divided into the metformin- and nonmetformin-treated subgroups. The percentage of elderly patients (P < 0.001), obese patients (P < 0.001), and menopausal patients (P < 0.001) as well as the percentage of patients with cardio-cerebrovascular complications (P < 0.001), negative PR (P < 0.001) expression, or low Ki67 expression (P = 0.001) tended to be higher in the diabetic group. In addition, these patients had later pathological stages (P < 0.001), more lymph node metastasis (P = 0.014), and a lower percentage of them were on the anthracycline-based chemotherapy regimen (P = 0.003). The diabetic group was further divided into the metformin and nonmetformin-treated subgroups. The pairwise comparison between the metformin-treated subgroup and the control group did not show a significant difference in the pathological stages (P = 0.0079). However, the HER-2 positive rate tended to be lower in the metformin-treated subgroup than in the nonmetformin-treated subgroup (P = 0.002). No significant difference was found in the lymph node status between the nonmetformin-treated subgroup and the control group (P = 0.057), while the nonmetformin-treated subgroup was associated with higher HER-2 positive expression (P = 0.002). The median follow-up time for this study was 68 months (10-120 months). In Kaplan-Meier analysis, The diabetic group predicted worse survival compared with the control group (P < 0.001) with 5-year survival rates of 79 and 82 %, respectively. The breast cancer mortality rates in the metformin-treated subgroup, the nonmetformin-treated subgroup, and the control group were significantly different (long-rank test, P < 0.001), and the 5-year survival rates were 88, 73, and 82 %, respectively. As shown in the multivariate survival analysis using Cox's regression model, compared with the control group, the metformin-treated subgroup was associated with lower mortality risk (HR 0.762; 95 % CI 0.6-0.968; P = 0.026), whereas the nonmetformin-treated subgroup was associated with higher mortality risk (HR 1.708; 95 % CI 1.461-1.997; P < 0.001). In conclusion, the diabetic group is associated with poor prognosis. Compared with the control group, the metformin-treated subgroup is associated with better clinical outcomes, while nonmetformin-treated subgroup with poorer prognosis. The selection of different antidiabetic drugs may impact the prognosis of breast cancer patients with diabetes.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Diabetes Mellitus , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Feminino , Seguimentos , Humanos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco
19.
Breast Cancer Res Treat ; 133(2): 473-85, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21947651

RESUMO

The purpose of the study was to detect the effect and possible mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) on the in vitro and in vivo growth of stem cells isolated from primary human breast cancer cells and cell lines MDA-MB-231 and MCF-7. Primary human breast cancer cells and MDA-MB-231 and MCF-7 cells were sorted in vitro using flow cytometry, and the ESA+, CD44+, CD24-/low cells were isolated as breast cancer stem cells (CSCs). The inhibitory effect of hUCMSCs on CSCs was examined using the Cell Counting Kit-8 cell proliferation and soft agar colony formation assay. In vivo tumor inhibition was studied using a severe combined immunodeficient xenograft mouse model transplanted with MDA-MB-231 breast CSCs. The expression of phosphoinositide 3-kinase (PI3K) and AKT was examined in the xenograft tumors using immunohistochemistry. The number of colonies formed by breast CSCs co-cultured with hUCMSCs at the bottom of soft agar was significantly lower than those formed by the control group (P < 0.01). Compared with the control group, the CSCs co-cultured with hUCMSCs showed a higher number of cells in the G2-M phase (P < 0.05) and an increased number of apoptotic cells (P < 0.01). The mice in the medium- and high-concentration hUCMSC treatment groups exhibited clearly reduced tumor volume and tumor weight, compared with the control group (P < 0.01). Compared with the saline group, the xenograft tumor tissues from the mice treated with different concentrations of hUCMSCs showed significantly reduced levels of PI3K and AKT proteins (P < 0.001). In conclusion, hUCMSC significantly inhibited the growth of breast CSCs in vitro and in vivo. The underlying mechanism is likely related to cell cycle arrest, induction of tumor cell apoptosis, and suppressed activities of PI3K and AKT protein kinases.


Assuntos
Neoplasias da Mama/metabolismo , Sangue Fetal/citologia , Células-Tronco Mesenquimais/metabolismo , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Cancer Epidemiol ; 36(1): 89-93, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21613000

RESUMO

BACKGROUND: Despite anecdotal evidence linking socioeconomic status and choices on surgical management in breast cancer patients in China, no scientific evaluations have ever been conducted. The objective of this study was to evaluate patient factors that influence patients' treatment options between breast cancer patients receiving breast-conserving therapy (BCT) and modified radical mastectomy (MRM). METHODS: A total of 268 stage I-II breast cancer patients treated with BCT in Tianjin Cancer Hospital, from January 2005 to January 2007, were compared with 200 randomly selected breast cancer patients (controls) treated with MRM. A personal health questionnaire (PHQ) was used to assess the factors that may affect the surgical decision making. Chi-squared test and multiple logistic regressions were used to examine factors associated with BCT. RESULTS: BCT patients who were younger and were more likely to live in urban areas had medical insurance, higher levels of education and family income. Patients with medical insurance coverage were approximately six times more likely to receive BCT than patients without medical insurance after controlling for other potentially confounding factors. Similar results were also observed for family income. The observed differences cannot be explained by clinical aspects of their disease, such as tumor stage, estrogen receptor, and lymph node involvement. CONCLUSION: Breast cancer patients' socioeconomic status, rather than their clinical condition, is the predominant factor in determining whether a breast cancer patient receives BCT or not. These results provide a snapshot on how socioeconomic status influences cancer care provision in China. Future efforts should be made towards reducing discrepancies in treatment options for cancer patients caused by social class and socioeconomic status.


Assuntos
Neoplasias da Mama/economia , Neoplasias da Mama/cirurgia , Adulto , Idoso , Neoplasias da Mama/patologia , Estudos de Casos e Controles , China , Feminino , Humanos , Mastectomia Radical Modificada/economia , Mastectomia Radical Modificada/estatística & dados numéricos , Mastectomia Segmentar/economia , Mastectomia Segmentar/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Classe Social , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
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