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1.
Br J Cancer ; 130(9): 1517-1528, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38459187

RESUMO

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.


Assuntos
Proliferação de Células , Neoplasias Colorretais , Progressão da Doença , Fator de Iniciação 4A em Eucariotos , Camundongos Nus , MicroRNAs , RNA Circular , beta Catenina , MicroRNAs/genética , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , RNA Circular/genética , Animais , Camundongos , beta Catenina/metabolismo , beta Catenina/genética , Proliferação de Células/genética , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , delta Catenina , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Masculino , Feminino , Movimento Celular/genética , Camundongos Endogâmicos BALB C
2.
Cancer Biol Ther ; 25(1): 2306674, 2024 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-38372700

RESUMO

DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in vitro. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant anti-oncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.


Assuntos
Adenina/análogos & derivados , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Azacitidina/farmacologia , RNA Mensageiro/genética , Metiltransferases , GTP Fosfo-Hidrolases , Proteínas Supressoras de Tumor , Dioxigenase FTO Dependente de alfa-Cetoglutarato
3.
Heliyon ; 9(11): e21043, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37928028

RESUMO

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development. Methods: Between 2018 and 2022, we retrospectively studied a total of 777 patients, comprising 339 patients with high-level cervical lesions and 313 patients with microinvasive or invasive cervical cancer. Overall, 1554 colposcopic images were put into the DeepLabv3+ model for learning. Accuracy, Precision, Specificity, and mIoU were employed to evaluate the performance of the model in the prediction of cervical high-level lesions and cancer. Results: Experiments showed that our segmentation model had better diagnosis efficiency than colposcopic experts and other artificial intelligence models, and reached Accuracy of 93.29 %, Precision of 87.2 %, Specificity of 90.1 %, and mIoU of 80.27 %, respectively. Conclution: The DeepLabv3+ model had good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnosis.

4.
Chem Biodivers ; 19(10): e202200767, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36098055

RESUMO

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.


Assuntos
Selaginellaceae , Humanos , Selaginellaceae/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Açúcares , Etanol , Extratos Vegetais
5.
Reprod Sci ; 26(12): 1618-1625, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30832539

RESUMO

The myometrium, especially the junctional zone (JZ), is now well documented to have a role in the pathogenesis of adenomyosis. Cannabinoid receptors have been shown to participate in the establishment of endometriosis and its pain perception. However, its relation to adenomyosis has not been identified yet. The aim of this study was to investigate the expression of cannabinoid receptor type I (CB1) and type II (CB2) in myometrium of uteri with and without adenomyosis and determine the correlation between their levels and clinical parameters of adenomyosis. We collected tissue samples of JZ and the outer myometrium from 45 premenopausal women with adenomyosis and 34 women without adenomyosis. CB1 and CB2 messenger RNA (mRNA) and protein expression levels were evaluated by the use of Western blotting and real-time quantitative polymerase chain reaction from all samples. Clinical information on the severity of dysmenorrhea and other data were collected. We found both CB1 and CB2 mRNA and protein levels in women with adenomyosis were significantly higher than those of controls, and CB1 expression levels in JZ were positively correlated with the severity of dysmenorrhea. These data suggest that cannabinoid receptor CB1 may be involved in the pathogenesis of dysmenorrhea in adenomyosis and may be a potential therapeutic target.


Assuntos
Adenomiose/metabolismo , Dismenorreia/metabolismo , Miométrio/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade
6.
Planta Med ; 85(9-10): 692-700, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30791058

RESUMO

Dammarane-type saponins, the main active ingredients of Panax notoginseng, have substantial neuroprotective effects in different animal models of neurodegenerative diseases. However, because these compounds have different structures, the level of protection provided by individual compounds varies, and highly active compounds can be selected based on structure-activity relationships. Glutamate is a major excitatory neurotransmitter that plays an important role in synaptic response development. However, excessive extracellular glutamate levels lead to neuronal dysfunctions in the central nervous system. Herein, we investigated the neuroprotective effects of nine saponins (compounds 1:  - 9: ) on glutamate-treated PC12 cells in the concentration range of 0.1 - 10 µM. The MTT assay revealed that these compounds increased cell viability to 65.6, 69.8, 76.9, 91.7, 74.4, 63.3, 59.9, 64.7, and 59.9%, respectively, compared with the glutamate-treated cells (44.6%). Protopanaxatriol (compound 4: ) was the most neuroprotective compound, and subsequent experiments revealed that pretreatment with compound 4: significantly reverses mitochondrial membrane potential collapse, increases superoxide dismutase activity, and decreases lactate dehydrogenase leakage, malondiadehyde levels, reactive oxygen species generation, and cell apoptosis. Compound 4: also decreased the Bax/Bcl-2 ratio, cleaved caspase-3, N-methyl-D-aspartic receptor 1, and Ca2+-/calmodulin-dependent protein kinase II expression, and inhibited glutamate-induced cytochrome C release and phosphorylation of apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38. Overall, the results indicate that protopanaxatriol has significant neuroprotective effects, and might be a promising neuroprotective agent for preventing and treating neurodegenerative diseases.


Assuntos
Ácido Glutâmico/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Panax notoginseng/química , Saponinas/química , Saponinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Malondialdeído/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Fosforilação/efeitos dos fármacos , Proteínas/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Saponinas/administração & dosagem , Triterpenos/química , Damaranos
7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 972-7, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30048092

RESUMO

Spine is one of the most important organs in the human body. One of the most commonly used method for the treatment of spinal diseases is the internal fixation and accurate placement of pedicle screw, which is a key factor of spinal surgery. However, due to the large differences as to the appearance of pedicles, it is hard to place the pedicle screw precisely, which will cause complication. Therefore, to find a new real-time intra-operative monitoring method with navigation is the direction of clinical application research. In this paper, a new method was firstly proposed. This method combined computer tomography (CT) values and near-infrared spectroscopy (NIRs) measurement data to guide the PS placement, and the relationship between NIRs parameters and CT values along the PS trajectory in vertebrae was investigated. First, we took pig vertebrae as samples and different puncture paths were planned. Second, a near-infrared monitoring device was utilized in experiments of fresh pig vertebrae to acquire the best NIRs monitoring pattern factors. Finally, the correlation function between NIRs data and CT values pattern factors was obtained. The results showed that CT values have a linear relationship with NIRs monitoring pattern factors, which provide references for real-time monitoring method in pedicle screw fixation surgery. This model can be applied in monitoring the pedicle screw implantation and alarming. The proposed method will be potential in improving the accuracy of PS placement and reduce the risk caused by the misplacement of pedicle screw.

8.
Mol Clin Oncol ; 2(6): 953-959, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25279180

RESUMO

Rechallenge chemotherapy with pemetrexed was shown to be efficient in malignant pleural mesothelioma; however, its role in non-small-cell lung cancer (NSCLC) has not been investigated. In this study, we retrospectively enrolled 31 patients with non-squamous NSCLC who had achieved disease control with initial pemetrexed treatment, followed by rechallenge with pemetrexed-based chemotherapy (PBC) upon disease progression. After the rechallenge, 5 patients (16.1%) achieved partial remission (PR), 17 (54.8%) achieved stable disease (SD) and 9 (29.1%) experienced progressive disease. The treatment was generally well tolerated, with a low rate of toxicity. The median progression-free survival (PFS) was 3.8 months with the rechallenge. Patients with a PFS of ≥10 months with initial PBC exhibited longer PFS and overall survival (OS) with the rechallenge compared to those with a PFS of <10 months with initial PBC (PFS: 6.2±0.33 vs. 3.1±0.26 months, respectively; P=0.011; and OS, 19.8±3.2 vs. 9.2±1.1 months, respectively; P=0.005). The time from the termination of initial PBC to disease progression was also associated with survival after the rechallenge. However, the response to initial PBC (PR vs. SD) did not affect PFS after the rechallenge. No significant differences were observed in thymidylate synthase expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene fusion, or epithelial growth factor receptor mutation status between pemetrexed-sensitive and pemetrexed-resistant patients. Our results demonstrated that rechallenge with PBC was well tolerated and survival after the rechallenge was associated with survival during initial PBC. Therefore, patients with a PFS of ≥10 months or time-to-disease progression ≥3 months may be considered as candidates for pemetrexed rechallenge.

9.
Zhonghua Jie He He Hu Xi Za Zhi ; 36(3): 162-8, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23856136

RESUMO

OBJECTIVE: To identify potential prognosis related clinical and molecular factors in malignant pleural mesothelioma (MPM). METHODS: Seventy-nine patients with MPM treated in Beijing Cancer Hospital from June 1996 to May 2012 were enrolled in this study. Clinical and pathological data were collected, including age, gender, smoking status, treatment, response, and molecular biomarkers such as thymidylate synthetase (TS) expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangement. The primary endpoint was overall survival (OS). SPSS 16.0 statistical analysis software was used for univariate analysis. The expression of TS was detected by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) was performed to detect EML4-ALK gene rearrangement. Efficacy of the chemotherapy regimen including pemetrexed was analyzed with these molecular biomarkers. RESULTS: The median survival time (MST) of all patients was 15.5 months (95% CI: 10.6 - 20.4). Univariate survival analysis revealed that treatment factors including receiving operation, systemic chemotherapy, pemetrexed-based chemotherapy and capability of receiving second (or above) line chemotherapy were significantly related with OS. The MST of patients receiving operation was 5.4 months (95% CI: 3.6 - 7.3), significantly shorter than the 17.7months (95% CI: 11.8 - 23.5) in those who didn't receive operation (P = 0.030). Patients receiving systemic chemotherapy had a longer MST of 18.0 months (95% CI: 12.3 - 23.8) as compared to the 7.9 months (95% CI: 1.1 - 14.7) in those who didn't (P = 0.001). The MST of pemetrexed-based chemotherapy was 21.9 months (95% CI: 14.1-29.7) compared with 8.8 months (95% CI: 4.2 - 13.4) of regimens without pemetrexed (P = 0.000). For patients capable of receiving second (or above) line chemotherapy the MST was longer (21.0 months, 95% CI: 12.7 - 29.3) than those who could not (12.1 month, 95% CI: 6.4 - 17.8 month), P = 0.022. For the 42 patients treated with pemetrexed-based chemotherapy, the objective response rate (ORR) was 33.3% (14/42), the disease control rate (DCR) was 78.6% (33/42), the median progression-free survival (PFS) was 4.8 months (95% CI: 3.6 - 6.0) and MST was 21.9 months (95% CI: 14.1 - 29.7). Twenty-nine patients provided adequate specimens for detection of TS expression and 6 cases (20.7%) were positive. EML4-ALK gene rearrangement was studied in 32 patients and 6 (18.8%) were positive. TS expression was found to be inversely related to PFS of pemetrexed-based chemotherapy (P = 0.041). The MST was 19.6 months (95% CI: 6.0 - 7.9) in EML4-ALK-positive patients and 9.57 months (95% CI: 2.7 - 4.3) in negative ones (P = 0.159). CONCLUSIONS: Systemic chemotherapy especially pemetrexed-based regimen was proved to be a superior option for MPM with a significantly prolonged OS. Correlation between TS expression or EML4-ALK rearrangement and outcome of pemetrexed-based chemotherapy for MPM may contribute to future individualized treatment, which needs further validation from large-scale prospective studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glutamatos/administração & dosagem , Guanina/análogos & derivados , Mesotelioma/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Neoplasias Pleurais/tratamento farmacológico , Timidilato Sintase/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Guanina/administração & dosagem , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma/metabolismo , Mesotelioma/mortalidade , Mesotelioma/patologia , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/metabolismo , Pemetrexede , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Prognóstico , Fatores de Risco , Adulto Jovem
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 35(5): 323-8, 2012 May.
Artigo em Chinês | MEDLINE | ID: mdl-22883988

RESUMO

OBJECTIVE: To investigate the frequency of epidermal growth factor receptor (EGFR) mutations and their correlation with the efficacy of tyrosine kinase inhibitors (EGFR-TKI) in advanced squamous cell lung cancer. METHODS: This retrospective study enrolled 79 patients with advanced squamous cell lung cancer who received EGFR-TKI at Department of Thoracic Medical Oncology in Peking University Cancer Hospital from June 2004 to June 2011. Among them, 67 patients had tissue and/or plasma EGFR exon 19 and 21 mutation detection in order to make an analysis on the relationship between EGFR mutation and the TKI's effect. RESULTS: The disease control rate (DCR) was 56% in all the patients. The median progression free survival (mPFS) and median overall survival (mOS) was 3.7 months (95%CI: 2.0 - 5.0) and 11.5 months (95%CI: 6.6 - 14.2), respectively. Of the 67 patients who received EGFR mutation detection, there were 31 patients harboring EGFR-mutation, for whom the DCR was 71% (22/31), and mPFS and mOS was 6.3 months (95%CI: 2.2 - 10.0) and 13.5 months (95%CI: 7.3 - 18.6) respectively. 36 patients' EGFR status were wild type, for whom the DCR was 44% (16/36), mPFS and mOS was 2.2 months (95%CI: 1.1 - 4.0) and 6.4 months (95%CI: 4.0 - 12.0). There were 17 patients who received erlotinib and 7 patients who received gefitinib as second or more line treatment. mPFS and mOS were 7.9 months and 15.8 months in the erlotinib group, respectively; and the mPFS and mOS were both 6.3 months in gefitinib group; the difference between the 2 groups did not reach statistical significance. Cox-regression analysis showed that EGFR mutation was significantly correlated with PFS and OS (P < 0.05, respectively). EGFR mutation was significantly correlated with DCR by Chi-square test, P < 0.05. CONCLUSIONS: EGFR mutation was a predictor for advanced squamous cell lung cancer to EGFR-TKI. However, the effect was inferior in advanced squamous cell lung cancer as compared to lung adenocarcinoma. Erlotinib tended to be superior to gefitinib.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Quinazolinas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
11.
Zhonghua Jie He He Hu Xi Za Zhi ; 35(2): 97-101, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22455964

RESUMO

OBJECTIVE: To evaluate the effect of pemetrexed plus platinum for chemotherapy-naive advanced non-small cell lung cancer (NSCLC), and to explore thymidylate synthetase (TS) expression as the predictive and prognostic factor for this treatment. METHODS: This retrospective study enrolled 51 patients with chemotherapy-naive advanced NSCLC (non-squamous) treated at Department of Thoracic Medical Oncology in Beijing Cancer Hospital from Jan 2008 to Oct 2009. All patients received pemetrexed plus platinum as first-line treatment. TS expression was detected in 30 patients who had enough tissue samples by immunohistochemistry. RESULTS: The objective response rate (ORR) was 37.3%. Median progression-free survival (PFS) was 5.3 months (95%CI: 3.9 - 6.7), and median overall survival (OS) was 19.0 months (95%CI: 11.6 - 26.4). Univariate analysis showed that gender, pathology, smoking status and response were significantly correlated with OS. Cox-regression analysis showed that pathology was an independent prognostic factor. Rate of Grade 3/4 adverse events was low. In 30 patients with enough tissue samples were available, TS expression positive rate was 33.3% (10/30). Chi-square test showed that TS expression was not associated with ORR. Multivariate analysis showed that pathology, response and TS expression (P = 0.003, 0.005 and 0.001, respectively) were the prognostic factors. CONCLUSION: The therapeutic effect and tolerance of pemetrexed plus platinum regiment were definite as first-line treatment for chemotherapy-naive advanced NSCLC, and TS expression was an independent prognostic factor.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Timidilato Sintase/análise , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Pemetrexede , Platina/administração & dosagem , Estudos Retrospectivos , Timidilato Sintase/metabolismo , Resultado do Tratamento , Adulto Jovem
12.
Chin J Cancer Res ; 23(2): 112-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23483659

RESUMO

OBJECTIVE: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease progression as second-line therapy (delayed group). METHODS: The study included 159 no-small-cell lung cancer (NSCLC) patients who received gefitinib or erlotinib as maintenance treatment in the immediate group (85 patients) or as second-line therapy in the delayed group (74 patients). The primary end point was progression-free survival (PFS). EGFR mutation status was detected using denaturing high-performance liquid chromatography (DHPLC). RESULTS: PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively (hazard ratio [HR], 0.99; 95% Confidence Interval [CI]: 0.69-1.42; P=0.947). In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group (HR, 0.48; 95% CI: 0.27-0.85; P=0.012). In patients with wild type EGFR, the risk for disease progression was comparable between the two groups (HR, 1.23; 95% CI: 0.61-2.51; P=0.564). No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival (OS) (26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI: 0.27 to 1.06; P=0.072). There was also no difference in the incidence of adverse events between the two groups. CONCLUSIONS: EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.

13.
Chin Med J (Engl) ; 124(21): 3510-4, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22340169

RESUMO

BACKGROUND: The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis. METHODS: We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes. RESULTS: There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P = 0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors. CONCLUSION: Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Plasmídeos/genética , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
14.
Zhongguo Zhen Jiu ; 29(6): 444-8, 2009 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19563189

RESUMO

OBJECTIVE: To observe the clinical therapeutic effect of combination of Source Point and Back-Shu Point on perimenopausal syndrome, and provide a new thought of therapy for perimenopausal syndrome. METHODS: Eighty cases of perimenopausal syndrome were randomly divided into a combination of Source Point and Back-Shu Point group and a routine acupuncture group, 40 cases in each group. The combination of Source Point and Back-Shu Point group was treated with acupuncture at Taixi (KI 3), Taichong (LR 3), Taibai (SP 3), Sanyinjiao (SP 6), Shenshu (BL 23), Ganshu (BL 18), Pishu (BL 20), Guanyuan (CV 4); and the routine acupuncture group was treated with acupuncture at Baihui (GV 20), Guanyuan (CV 4), Shenshu (BL 23), Taixi (KI 3), San-yinjiao (SP 6). The Kupperman score and the changes of serum estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were observed before and after treatment in the two groups. RESULTS: The total effective rate of 92.5% in the combination of Source Point and Back-Shu Point group was superior to 80.0% in the routine acupuncture group, with a significant difference (P < 0. 05); the Kupperman score of 24. 85 +/- 8.35 in the combination of Source Point and Back-Shu Point group was significantly decreased as compared with 35.38 +/- 9.83 in the routine acupuncture group (P < 0.05) after treatment; the contents of E2, FSH and LH in the combination of Source Point and Back-Shu Point group were significantly improved after treatment, and with a significant difference compared to the routine acupuncture group (P < 0.01, P < 0.05). CONCLUSION: Combination of Source Point and Back-Shu Point has a benign regulation function for E2, FSH and LH, and can significantly improve the Kupperman score, is superior to routine acupuncture for perimenopausal syndrome.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Perimenopausa/sangue , Acupuntura/métodos , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Síndrome , Resultado do Tratamento
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 28(7): 1154-6, 2008 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-18676250

RESUMO

OBJECTIVE: To investigate the protective effects of estrogen on the mitochondria in human umbilical vascular endothelial cells (HUVECs). METHODS: HUVECs were exposed to H2O2 at 250 micromol/L for 4 h with or without pretreatment with 17-estradiol (E2) and ICI182780. Complex IV activity of the cells was measured with chromometry, and 2, 7-dichlorofluorescein diacetate (DCFH-DA) was used to determine intracellular reactive oxygen species (ROS). Intracellular adenosine triphosphate (ATP) level was quantified with a luciferin- and luciferase-based assay. RESULTS: Compared to the blank control group, H2O2 caused a decrease in complex IV activity, intracellular ATP level, and the cell viability, but elevated intracellular ROS. E2 pretreatment of cells significantly attenuated these effects of H2O2 exposure. ICI182780 administered prior to E2 pretreatment antagonized the protective effects of E2 against H2O2 exposure. CONCLUSION: E2 offers mitochondrial protective effects on HUVECs, which is mediated by the estrogen receptors.


Assuntos
Células Endoteliais/efeitos dos fármacos , Estrogênios/farmacologia , Mitocôndrias/efeitos dos fármacos , Veias Umbilicais/citologia , Células Cultivadas , Citoproteção/efeitos dos fármacos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/farmacologia , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Espécies Reativas de Oxigênio/metabolismo
16.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 24(5): 381-4, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19119643

RESUMO

OBJECTIVE: To investigate the surface markers of adipose-derived stromal cells (ASCs) with high potential of adipogenic differentiation for increasing efficiency of adipose tissue engineering with selected seeds cells. METHODS: ASCs were harvested from human adipose tissue by collagenase digestion. After proliferation and adipogenic induction of ASCs, the mature induced adipocytes floating in the induction medium were collected. Ceiling culture was used to culture adipocytes and then dedifferentiated adipocytes was obtained at the ceiling. The reproductive activity, adipogenic differentiation potency and expression of surface markers were compared between the dedifferentiated adipocytes and ASCs. RESULTS: The reproductive activity between the dedifferentiation adipocytes and ASCs were similar. The potential of adipogenic differentiation of the dedifferentiated adipocytes was stronger than that of the ASCs. The expression of cell surface markers of both cells were almost the same. But the CD54 positive expression in dedifferentiated adipocytes was higher than that in ASCs. CONCLUSION: The CD54 expression maybe closely associated with high potential of adipogenic differentiation of dedifferentiated adipocytes. CU54 maybe the specific identification of cell surface marker of ASCs with high adipogenic differentiation.


Assuntos
Adipócitos/citologia , Desdiferenciação Celular , Células Estromais/citologia , Tecido Adiposo/citologia , Antígenos de Superfície , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , Humanos , Engenharia Tecidual/métodos
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