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1.
World J Surg Oncol ; 20(1): 189, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676669

RESUMO

BACKGROUND: Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC. METHODS: We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated, and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression. RESULTS: Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and a-fetoprotein (AFP) were independently associated with MVI: DL-MVI (odds ratio [OR] = 35.738; 95% confidence interval [CI] 14.027-91.056; p < 0.001), AFP (OR = 4.634, 95% CI 2.576-8.336; p < 0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824. CONCLUSIONS: Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Microvasos/patologia , Invasividade Neoplásica/patologia , Estudos Retrospectivos , alfa-Fetoproteínas
2.
J Cell Physiol ; 234(2): 1827-1841, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30191949

RESUMO

Breast cancer remains one of the foremost primary causes of female morbidity and mortality worldwide. During the current study, the effect of miR-590-5p and paired-like homeodomain transcription factor 2 (PITX2) on proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of human breast cancer via the Wnt-ß-catenin signaling pathway was investigated. Breast cancer-related genes and related signaling pathways were obtained from KEGG database. The PITX2 regulatory microRNA was predicted. To define the contributory role by which miR-590-5p influences the progression of breast cancer, the interaction between miR-590-5p and PITX2 was explored; the proliferation, invasion, and migration abilities as well as the tumor growth and metastasis in nude mice were detected following the overexpression or silencing of miR-590-5p. PITX2 was determined to share a correlation with breast cancer and miR-590-5p was selected for further analysis. PITX2, Wnt-1, ß-catenin, N-cadherin, and vimentin all displayed higher levels, while miR-590-5p and E-cadherin expression were lower among breast cancer tissues than in the adjacent normal tissue. After overexpression of miR-590-5p or si-PITX2, the expression of E-cadherin was markedly increased, decreases in the expression of Wnt-1, ß-catenin, N-cadherin, and vimentin, as well as inhibited cell proliferation, invasion, migration, metastasis, and EMT were observed. This study provides evidence suggesting that the transfection of overexpressed miR-590-5p can act to alleviate the effects of breast cancer demonstrating an ability to inhibit the processes of cell proliferation, migration, and invasion as well as EMT by suppressing the expression of PITX2 and activation of the Wnt-ß-catenin pathway.


Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal , MicroRNAs/metabolismo , Via de Sinalização Wnt , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Homeobox PITX2
3.
Cancer Sci ; 110(11): 3543-3552, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541611

RESUMO

Poly ADP-ribose polymerase inhibitors (PARPi) have shown promising therapeutic efficacy in triple-negative breast cancer (TNBC) patients. However, resistance ultimately develops, preventing a curative effect from being attained. Extensive investigations have indicated the diversity in the mechanisms underlying the PARPi sensitivity of breast cancer. In this study, we found that DNA damage binding protein 2 (DDB2), a DNA damage-recognition factor, could protect TNBC cells from PARPi by regulating DNA double-strand break repair through the homologous recombination pathway, whereas the depletion of DDB2 sensitizes TNBC cells to PARPi. Furthermore, we found that DDB2 was able to stabilize Rad51 by physical association and disrupting its ubiquitination pathway-induced proteasomal degradation. These findings highlight an essential role of DDB2 in modulating homologous recombination pathway activity and suggest a promising therapeutic target for TNBC.


Assuntos
Quebras de DNA de Cadeia Dupla , Proteínas de Ligação a DNA/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Rad51 Recombinase/metabolismo , Reparo de DNA por Recombinação , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Reparo do DNA , Proteínas de Ligação a DNA/deficiência , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Ubiquitinação
4.
Zhonghua Nan Ke Xue ; 25(7): 626-631, 2019 Jul.
Artigo em Zh | MEDLINE | ID: mdl-32223104

RESUMO

OBJECTIVE: To investigate the clinical therapeutic effects of sacral nerve magnetic stimulation (SNMS) combined with extracorporeal shockwave (ECSW) in the treatment of type-ⅢB chronic prostatitis. METHODS: This study included 65 cases of type-ⅢB chronic prostatitis treated in Renji Hospital between March 2017 and August 2018. The patients were aged 34.56 + 7.47 years and had an average disease course of 12.95 + 10.73 months. We randomly assigned the patients to an experimental (n = 33) and a control group (n = 32) to be treated by SNMS+ECSW and biofeedback combined with electrical stimulation, respectively, qd alt, 40 minutes once, for a total of 24 times. Before and after 4 and 8 weeks of treatment, we obtained the NIH-CPSI scores, maximum urinary flow rate (Qmax), average urinary flow rate (Qavg), Self-Rating Depression Scale (SDS) scores and Self-Rating Anxiety Scale (SAS) scores of the patients, recorded their adverse reactions and compared the clinical therapeutic effects between the two groups of patients. RESULTS: After treatment, the experimental group showed significant improvement in the pain score, urination score, quality of life (QOL) score and NIH-CPSI total scores in comparison with the baseline (P < 0.05), even more significant after 8 than after 4 weeks of treatment (P < 0.05), and in all the indexes as compared with the control group (P < 0.05). Qmax and Qavg were remarkably improved at 8 weeks (P < 0.05) and so were SDS and SAS scores at 4 and 8 weeks (P < 0.05), even more significantly in the experimental than in the control group (P < 0.05). Among the 33 patients in the experimental group, 25 (75.8%) responded (14 [42.4%] cured or with excellent effect), with a significantly higher effectiveness rate than the control group (7[46.9%], P < 0.01). No obvious adverse events were observed in any of the patients during the treatment. CONCLUSIONS: SNMS+ECSW can effectively improve the clinical symptoms and QOL of the patients with type-ⅢB chronic prostatitis, without causing obvious adverse reactions. Its long-term therapeutic effect, however, remains to be further studied.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Magnetoterapia , Prostatite/terapia , Adulto , Doença Crônica , Ondas de Choque de Alta Energia , Humanos , Masculino , Qualidade de Vida
5.
J Mater Sci Mater Med ; 29(1): 6, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29242993

RESUMO

Tissue engineering technology is applicable for study of nerve regeneration after spinal cord injury. Many natural and artificial scaffold are not applicable because of poor mechanical properties and cell compatibility. Polypeptides with fine three-dimensional structure and cell compatibility and are widely used in tissue engineering research. The purpose of this study was to verify the neuronal differentiation of neural stem cells by using self-polymerize dendritic polypeptide for spinal cord tissue engineering. Neural stem cells were isolated from cerebral cortex of neonatal SD rats.Conventional media was triggered the 1wt% nano peptide solution self polymerizated to formed a nano gel. The gel was tested by scanning electron microscope and transmission electron microscope. Neural stem cells were inoculated onto gel or on Polylysine-coated slides with fetal bovine serum or not. SD rats were randomized divided into four groups. neural stem cells and self-polymerized peptide were transplanted into spinal cord injury models. Then we test the Density of NF-positive axons in the spinal cord injury area at 8 weeks after surgery and MS score of the locomotive function of hind limbs among mice of four groups. Neural stem cells were showed anti Nestin (+), anti NSE (+), anti GFAP (+). The gel tested by scanning electron microscope was showed thick wall structure, another one tested by transmission electron microscope was showed self-polymerized dendritic nanofibers, which contains several spacings. The cells in serum group were differentiate into neurons, but non serum group were not. These results suggest that the self-assembling peptide nanofiber scaffold(SAPNS) were cytocompatible to neural stem cells which were differentiated into neurons. A large number of axonal regeneration and recovery of joint function of hind limb were appeared. The self-polymerized Peptide maybe used as practical tissue engineering materials as future.


Assuntos
Regeneração Nervosa , Neurônios/citologia , Peptídeos/química , Medula Espinal/patologia , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Animais Recém-Nascidos , Axônios/patologia , Axônios/fisiologia , Fenômenos Biomecânicos , Diferenciação Celular , Dendrímeros/química , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Células-Tronco Neurais/citologia , Polímeros/química , Ratos , Ratos Sprague-Dawley
6.
Carcinogenesis ; 36(9): 1061-70, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26116623

RESUMO

Use of the conventional cancer chemotherapy (i.e. vincristine) is limited in tumor cells exhibiting pre-existing or acquired resistance. Here, we found that C6 ceramide (C6) dramatically sensitized vincristine's activity. In vitro, C6 and vincristine coadministration induced substantial necrosis and apoptosis in multiple human cancer cell lines, which were accompanied by a profound AMP-activated protein kinase (AMPK) activation, subsequent p53 activation, mTORC1 inactivation and Bcl-2/HIF-1α downregulation. Such synergistic effects were attenuated by AMPK inactivation through genetic mutation or short hairpin RNA silencing. Coadministration-activated p53 translocated to mitochondria, and formed a complex with cyclophilin-D, leading to mitochondrial permeability transition pore opening and cell necrosis. Disrupting p53-Cyp-D complexation through pharmacological or genetic means reduced costimulation-induced cytotoxicity. In vivo, a liposomal C6 was synthesized, which dramatically enhanced the antiproliferative activity of vincristine on HCT-116 or A2780 xenografts. Together, C6 sensitizes vincristine-induced anticancer activity in vivo and in vitro, involving activating AMPK-p53 signaling.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ceramidas/farmacologia , Neoplasias/tratamento farmacológico , Proteína Supressora de Tumor p53/metabolismo , Vincristina/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Ciclofilinas/metabolismo , Regulação para Baixo , Sinergismo Farmacológico , Células HCT116 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Potencial da Membrana Mitocondrial , Camundongos , Camundongos SCID , Mitocôndrias/fisiologia , Complexos Multiproteicos/metabolismo , Necrose/induzido quimicamente , Transplante de Neoplasias , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Transplante Heterólogo , Proteína Supressora de Tumor p53/genética
7.
Zhongguo Zhong Yao Za Zhi ; 38(7): 937-42, 2013 Apr.
Artigo em Zh | MEDLINE | ID: mdl-23847932

RESUMO

According to the process of the technical specification (TS) design for the fourth national survey of the Chinese materia medica resources (CMMR), we analyzed the assignment and objectives of the national survey and pointed out that the differences about CMMR management around China, the distribution of CMMR and their habitat, the economic and technological level, and even enthusiasm and initiative of the staff, etc. are the most difficult points for TS design. And we adopt the principle of combination of the mandatory and flexibility in TS design. We fixed the key points which would affect the quality of national survey first, then proposed the framework of TS which including 3 parts of organization and 11 parts of technique itself. The framework will serve and lead the TS preparation, which will not only provide an action standard to the national survey but will also have a profound influence to the popularization and application of the survey technology of CMMR. [Key words]


Assuntos
Química Farmacêutica/normas , Conservação dos Recursos Naturais , Medicamentos de Ervas Chinesas/normas , Materia Medica/normas , Química Farmacêutica/legislação & jurisprudência , Química Farmacêutica/métodos , China , Coleta de Dados , Medicamentos de Ervas Chinesas/química , Materia Medica/química , Controle de Qualidade , Recursos Humanos
8.
Zhongguo Zhong Yao Za Zhi ; 38(16): 2653-6, 2013 Aug.
Artigo em Zh | MEDLINE | ID: mdl-24228581

RESUMO

According to National Census for Water, National Population Census, National Land and Resources Survey, and work experience of experimental measures for national Chinese materia medica resources(CMMR) survey,the national CMMR survey at the county level is the key point of whole survey, that includes organization and management, field survey, sorting data three key links. Organization and management works of national CMMR survey needs to finish four key contents, there are definite goals and tasks, practicable crew, preparation directory, and security assurance. Field survey works of the national CMMR survey needs to finish five key contents, there are preparation works for field survey, the choice of the key survey area (samples), fill in the questionnaire, video data collection, specimen and other physical collection. Sorting data works of the national CMMR survey needs to finish tree key contents, there are data, specimen and census results.


Assuntos
Coleta de Dados , Materia Medica/química , Materia Medica/provisão & distribuição , Medicina Tradicional Chinesa , Química Farmacêutica , China
9.
Zhongguo Zhong Yao Za Zhi ; 38(19): 3223-5, 2013 Oct.
Artigo em Zh | MEDLINE | ID: mdl-24422381

RESUMO

Focusing on the problems of Chinese materia medica resources,and combining with the national Chinese materia medica resources survey, the paper probes into monitoring mechanism of Chinese materia medica resources. The establishment of the monitoring mechanism needs one organization and management agencies to supervise and guide monitoring work, one network system to gather data information, a group of people to perform monitoring work, a system of technical methods to assure monitoring work scientific and practical, a series of achievements and products to figure out the methods for solving problems, a group of monitoring index system to accumulate basic data, and a plenty of funds to keep normal operation of monitoring work.


Assuntos
Materia Medica , Medicamentos de Ervas Chinesas , Humanos
10.
Zhongguo Zhong Yao Za Zhi ; 38(5): 625-8, 2013 Mar.
Artigo em Zh | MEDLINE | ID: mdl-23724663

RESUMO

The planning of the fourth national survey on Chinese materia medica resources shall follow the requirement of "carrying out the national survey on Chinese materia medica resources, strengthening the construction of Chinese materia medica resources monitoring and information network" which is according to the document issued by the State Council. Based on the responsibilities of State Administration of Traditional Chinese Medicine which is "organizing the survey, promoting the resource-protection, keeping development and rational utilization", combined with the key problems that need to be solved in current medicinal industry, the related instructions issued by central leadership and the recommendations from NPC delegates, CPPCC members and experts, the planning shall make overall plans and top-level design for the new round of national survey on Chinese materia medica resources.


Assuntos
Coleta de Dados , Medicamentos de Ervas Chinesas/provisão & distribuição , Materia Medica/provisão & distribuição , China , Bases de Dados de Produtos Farmacêuticos , Objetivos , Projetos de Pesquisa , Controle Social Formal
11.
J Oncol ; 2023: 3876342, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153834

RESUMO

Gastric cancer (GC) is the third most lethal and fifth most common cancer in the world. In a variety of cancers, the hexokinase domain component 1 (HKDC1) is carcinogenic. This study was to investigate into how HKDC1 contributes to the development and progression of GC. Three different datasets (GSE103236, GSE13861, and GSE55696) were extracted from the Gene Expression Omnibus (GEO) database and then analyzed using the sva package. The R software was used to identify 411 differentially expressed genes (DEGs) in the pooled dataset. We discovered 326 glycolysis-related genes (glyGenes) in the cancer genome atlas-stomach adenocarcinoma (TCGA-STAD) cohort using gene set enrichment analysis set (GSEA). HKDC1 is one of the most prevalent glyGenes in GC tumor tissues and cells, as seen in the Venn diagram. According to the results of the Cell Count Kit-8 assay, the proliferation of AGS and MKN-45 cells decreased when HKDC1 was knocked down. Lack of HKDC1 in cells enhanced oxygen consumption and decreased glycolytic protein expression while suppressing glucose absorption, lactate production, ATP level, and extracellular acidification ratio. As an oncogene in gastric cancer development, HKDC1 influences cell proliferation and glycolysis.

12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(9): 2555-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22097870

RESUMO

The sudangrass (Sorghum sudanense) and ryegrass (Lolium multi florum L.) rotation is a new type of cropping system, which has developed rapidly in recent years in the south of China. The contents of nutritional elements for forage grass in the sudangrass and ryegrass rotation system were determined by ICP-AES. The results showed that there were abundant and essential nutritional elements for animals in sudangrass and ryegrass. The contents of P, K, Ca, Mg, S, Fe, B, Cu, Zn and Mn for sudangrass were 0.20% -0.29%, 1.94%-2.57%, 0.62%-0.97%, 0.39%-0.69%, 0.12%-0.18%, 108.35-180.12, 3.04-5.96, 6.17-10.02, 20.37-31.36 and 46.80-101.29 mg x kg(-1), respectively. The contents of P, K, Ca, Mg, S, Fe, B, Cu, Zn, Mn for ryegrass were 0.39%-0.70%, 3.77%-5.07%, 0.61%-0.84%, 0.28% -0.47%, 0.32%-0.41%, 291.65- 632.20, 2.13-3.23, 13.29-15.19, 30.73-42.98 and 92.08-156.04 mg x kg(-1), respectively, and there were differences between various periods in nutritional elements in the two forage grasses. The application of ICP-AES could reflect fast and efficiently the content of nutritional elements for forage grass as animals feed.


Assuntos
Lolium/química , Sorghum/química , Ração Animal , China , Valor Nutritivo , Espectrofotometria Atômica
13.
Zhongguo Gu Shang ; 34(2): 153-6, 2021 Feb 25.
Artigo em Zh | MEDLINE | ID: mdl-33666003

RESUMO

OBJECTIVE: To investigate specific technique and clinical effects of closed folding top consolidation maneuver combined with splint fixation maneuver for consolidation and cedar bark external fixation splint for the treatment of double fractures of distal ulna and radius in children. METHODS: From January 2017 to December 2019, 17 children with double fractures of distal ulna and radius were treated with closed folded apex consolidation maneuver, including 13 males and 4 females, aged from 4 to 11 years old with an average of (7.29±2.34) years old. The fractures were fixed with cedar bark splint and followed up for 6 months, and alignment of fracture was evaluated according to the latest X-rays by follow up, and function of the affected limbs was evaluated by Anderson forearm function evaluation criteria. RESULTS: Fifteen of 17 children were successfully reset immediately, and 2 children were successfully reset again. The average fixed time was (25.00±3.35) days. At 6 months of follow up, 12 patients got excellent results, 3 good, 2 fair, and 0 poor according to Anderson forearm function evaluation criteria. The position of all children were larger than 3/4, and 10 children were received anatomical reduction, alignment of 4 children was less than 10°, 3 children was less than 15°. No complications such as fracture displacement, nonunion, compartment syndrome, and forearm rotation dysfunction occurred. CONCLUSION: Restoration of distal radius double fracture in children with the combination of the closed folding and top fixation maneuver and splint fixation maneuver has advantages of higher success rate, lower complications, which could reduce operating difficultyand pain of patients.


Assuntos
Fraturas do Rádio , Fraturas da Ulna , Idoso , Criança , Pré-Escolar , Feminino , Fixação de Fratura , Fixação Interna de Fraturas , Humanos , Masculino , Rádio (Anatomia) , Fraturas do Rádio/terapia , Contenções , Resultado do Tratamento , Ulna
14.
Zhonghua Nan Ke Xue ; 16(9): 790-3, 2010 Sep.
Artigo em Zh | MEDLINE | ID: mdl-21171261

RESUMO

OBJECTIVE: To evaluate and compare the clinical efficacy and safety of the highly selective alpha receptor antagonist tamsulosin and its combination with the M receptor antagonist tolterodine in the treatment of refractory lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). METHODS: We included in this study 184 BPH patients with refractory LUTS with the disease course of 4 weeks to 2 years, whose LUTS were not alleviated after a week's treatment with tamsulosin. The patients were randomly divided into Groups A and B, the former (n=89) treated with tamsulosin at 0.2 mg qd and the latter (n=95) given tolterodine at 2 mg bid in addition to tamsulosin medication, both for 4 weeks. Scores on IPSS, QOL and Qmax were obtained before and after the treatment, and the improvement of LUTS evaluated after the medication. RESULTS: The tamsulosin group showed no significant differences before and after the treatment in the scores on IPSS (13.23 +/- 4.39 vs. 12.21 +/- 4.07), QOL (4.23 +/- 1.27 vs 3.53 +/- 0.95) and Qmax ([12.3 +/- 8.39] ml/s vs. [14.1 +/- 8.62] mls) (P > 0.05), while the combination group exhibited significantly higher scores on IPSS and QOL and lower score on Qmax after the medication than before it (IPSS: 14.45 +/- 5.31 vs. 6.56 +/- 2.03, P < 0.05; QOL: 4.45 +/- 0.79 vs. 2.34 +/- 0.73, P < 0.05; Qmax: [11.4 +/- 9.21] ml/s vs. [15.5 +/- 8.35] ml/s, P < 0.01). No severe complications were found in any of the cases. CONCLUSION: Combination of tamsulosin and tolterodine can significantly alleviate refractory LUTS and improve QOL without causing serious adverse events in BPH patients.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Cresóis/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Fenilpropanolamina/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Tansulosina , Tartarato de Tolterodina , Resultado do Tratamento
15.
Zhonghua Zhong Liu Za Zhi ; 31(2): 108-13, 2009 Feb.
Artigo em Zh | MEDLINE | ID: mdl-19538885

RESUMO

OBJECTIVE: To establish a method for SNP genotyping of multi-genes by allele-specific oligonucleotide probe ligation mediated by a thermostable ligase, and to explore the genetic polymorphisms of drug-metabolizing enzymes in breast cancer patients and their association with chemotherapeutic responses. METHODS: 10 SNP loci of enzyme genes related to chemotherapeutic drugs such as taxanes, anthracyclines and cyclophosphamide were selected, and were genotyped for blood samples from 126 breast cancer patients by the established method. Their correlations with therapeutic responses were retrospectively evaluated. RESULTS: The lower detection limit of genomic DNA by this developed method was 6.25 ng. The fluorescent peak locations of ligation products on ABI PRISM 377 DNA sequencer were accurate and consistent with prospective sizes in bases (Bias range 0.08 - 0.69 bp, x(-) = 0.31 bp, s = 0.18 bp). Same genotyping results were obtained for repeat tests of 8 random samples, which were further confirmed by sequencing analysis. The 10 SNP loci were polymorphic of different frequency in the breast cancer patients. The combinations with GSTP1 genotypes and GSTM1 genotypes were related to anthracycline-based chemotherapy efficacy (P = 0.037), and the low GSTs activity group (GSTP1 variant allele + GSTM1 null) showed the best effects (85.7%). GSTM1 genotypes and their combinations with GSTP1 and/or CYP3A5*3 genotypes were related to taxane-based therapy efficacy (P < 0.05 for all), and both the low GSTs activity group and the drug slow-metabolising group (low GSTs activity group + CYP3A5*3 wild allele) showed better effects (100%). CONCLUSION: The established method is reliable and applicable in multiplex SNPs genotyping of multi-genes. SNPs combination may have a better clinical application value for prediction of chemotherapeutic responses.


Assuntos
Neoplasias da Mama/genética , Análise Mutacional de DNA/métodos , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Citocromo P-450 CYP3A/genética , Feminino , Frequência do Gene , Genótipo , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Estudos Retrospectivos , Taxoides/uso terapêutico , Resultado do Tratamento
16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(9): 2571-3, 2009 Sep.
Artigo em Zh | MEDLINE | ID: mdl-19950678

RESUMO

The object of the present study was to investigate ten necessary mineral elements in different varieties of rapeseed by ICP-MS. Thirty three samples of double-low (low in both glucosinolates and erucic acid) rapeseed (DLR) and 12 samples of double-high rapeseed (DHR) in the Yangtze River Valley were collected. The results showed that rapeseed contained many kinds of necessary elements, and there was a difference between DLR and DHR The average concentrations of P, K, Ca, Mg, S, Fe, Mn, Cu, Zn and B in DLR were 6.26 mg x g(-1), 10.17 mg x g(-1), 6.75 mg x g(-1), 4.82 mg x g(-1), 4.52 mg x g(-1), 96.20 microg x g(-1), 37.10 microg x g(-1), 3.84 microg x g(-1), 41.61 microg x g(-1) and 12.16 microg x g(-1), respectively, while for the mineral elements in DHR, the average values were 5.97 mg x g(-1), 10. 14 mg x g(-1), 6.31 mg x g(-1), 4.50 mg x g(-1), 9.06 mg x g(-1), 77.03 microg x g(-1), 49.86 microg x g(-1), 3.72 microg x g(-1), 40.58 microg x g(-1) and 11.79 microg x g(-1). The contents of most elements in DLR were higher than those in DHR, such as P, K, Ca, Mg, Fe, Cu, Zn and B. Furthermore, the differences in Ca, Mg and Fe contents between the two varieties were significant. It was concluded that the difference in concentrations of mineral elements can be regarded as a necessary factor for popularizing double-low rapeseed in the Yangtze River Valley.


Assuntos
Brassica rapa/química , Minerais/análise , Espectrometria de Massas
17.
Biomed Pharmacother ; 109: 2327-2334, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551491

RESUMO

OBJECTIVE: Chemoresistance has been a major problem in cancer chemotherapy. The present study aimed to investigate the effect of Rosmarinic acid (RA) on chemoresistance to 5-Fu and its molecular mechanism in gastric carcinoma. METHODS: CCK8 cell proliferation and apoptosis assay were used to evaluate the effect of RA on chemoresistance to 5-Fu in GC cells. RNA microarray was used to identify miRNA involved. Expression level of miRNA in GC cells was determined by RT-PCR. Down- or up-regulating of miRNA in the GC cells was performed by transfection of RNA interference or expression vectors in the GC cells. Double luciferase reporter assay was used to verify miRNA target genes. Expression of P-glycoprotein and Bax was analyzed with Western blot. RESULTS: RA treated SGC7901/5-Fu cells showed significant increased chemosensitivity to 5-Fu. The IC50 of 5-Fu was significantly reduced in RA treated SGC7901/5-Fu cells (70.43 ± 1.06 µg/mL) compared to untreated SGC7901/5-Fu cells (208.6 ± 1.09 µg/mL) (P < 0.05). Apoptosis rate was significantly increased in RA+5-Fu treated SGC7901/5-Fu cells compared to 5-FU treatment alone (P < 0.01). Two miRNAs, namely miR-642a-3p and miR-6785-5p, were identified to be involved in the chemo-sensitizing effect of RA in the SGC7901/5-Fu cells. RA treated SGC7901/5-Fu cells showed reduced expression levels of miR-642a-3p and miR-6785-5p compared to untreated SGC7901/5-Fu cells (P < 0.05). Down- or up-regulation of miR-6785-5p increased or reduced chemosensitivity of gastric carcinoma cells to 5-Fu, respectively. RA treated SGC7901/5-Fu and the SGC7901/5-Fu-Si cells showed significantly increased FOXO4 expression (P < 0.01). Double luciferase reporter assay confirmed miR-6785-5p directly targets FOXO4 to regulate its expression. RA significantly reduced P-gp expression and increased Bax expression in SGC7901/5-Fu and the SGC7901/5-Fu-Si cells (P < 0.05). CONCLUSION: RA enhances chemosensitivity of resistant gastric carcinoma SGC7901 cells to 5-Fu by downregulating miR-6785-5p and miR-642a-3p and increasing FOXO4 expression. These study suggest the potential for RA as a multidrug resistance-reversing agent in GC.


Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/biossíntese , Antimetabólitos Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Carcinoma/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Fatores de Transcrição Forkhead , Marcação de Genes/métodos , Humanos , MicroRNAs/antagonistas & inibidores , Ácido Rosmarínico
18.
Zhonghua Nan Ke Xue ; 14(1): 38-41, 2008 Jan.
Artigo em Zh | MEDLINE | ID: mdl-18297810

RESUMO

OBJECTIVE: To evaluate the expression of CD117 in human testicular germ cell tumors and its value in the differential diagnosis of seminoma and nonseminoma. METHODS: Seventy-four human testicular germ cell tumor specimens were studied by ABC kit immunohistochemical staining detection using CD117 monoclonal antibodies. The immunoreaction scores (IRS) of all the specimens were calculated and analysed for their clinical significance. RESULTS: Among the 74 germ cell tumors, 31 out of 32 (9 6.9%) seminomas showed positive staining of the CD117 mostly on the cell membrane. Four of 31 (12.9%) nonseminomas displayed a weak positive staining of CD117 only in the cytoplasm of a few cells. In 10 of 11 mixed germ cell tumors, a relatively weak expression of CD117 was shown only in the seminoma component. The CD117 expression was diagnostically decreased from seminoma to mixed seminoma and to nonseminoma successively, with IRS of 6.82 +/- 2.76, 1.25 +/- 0.42 and 0.60 +/- 0.16, respectively. There was a significant difference in the CD117 expression between seminoma and nonseminoma (P < 0.05). CD 117 proteins were positively expressed in all the 20 specimens of the normal testis. CONCLUSION: The detection of CD117 by immunohistochemical staining using CD117 monoclonal antibodies is a newly developed useful method for differentiating seminoma and nonseminoma.


Assuntos
Neoplasias Embrionárias de Células Germinativas/metabolismo , Proteínas Proto-Oncogênicas c-kit/biossíntese , Seminoma/metabolismo , Neoplasias Testiculares/metabolismo , Adolescente , Adulto , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Valor Preditivo dos Testes , Seminoma/diagnóstico , Neoplasias Testiculares/diagnóstico
19.
Cancer Biomark ; 23(3): 405-418, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30223390

RESUMO

OBJECTIVE: Gastrulation brain homeobox 2 (GBX2), a gene involved in mid/hindbrain region, has been revealed as one of the oncogene associated with certain cancers, as an example being prostate cancer. However, despite years of worldwide research, the underlying mechanism of GBX2 as well as its significance in breast cancer still remains unclear. Therefore, the present study evaluates the abilities of GBX gene silencing providing for the proliferation, invasion and angiogenesis of breast cancer cells by way of the Wnt/ß-catenin signaling pathway. METHODS: We employed a microarray analysis to screen out differentially expressed genes relative to breast cancer. Moreover, we retrieved GBX2 expression in breast cancer to find out the relationship between GBX2 expression and prognosis in breast cancer. We performed RT-qPCR to screen out cell lines with high GBX2 expression. Subsequently, both RT-qPCR and western blot analysis were employed so as to measure the combination of the mRNA and protein expressions of GBX2, ß-catenin, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. The effect that GBX2 gene silencing and the Wnt/ß-catenin signaling pathway had on cell proliferation, invasion, angiogenesis, and tumorigenic ability were evaluated. RESULTS: GBX2 gene was also identified having played a role in breast cancer development due to its association with the Wnt/ß-catenin signaling pathway. GBX2 gene silencing was found to be an inhibitor for the mRNA and protein expressions regulating ß-catenin, VEGF, MMP-2, and MMP-9. Cell proliferation, invasion, angiogenesis, as well as tumorigenic ability in breast cancer were investigated and found to have been suppressed by the GBX2 gene silencing or inactivation of the Wnt/ß-catenin signaling pathway. CONCLUSION: The study has made an attempt to provide evidence to the idea that GBX2 gene silencing has an inhibition effect on the proliferation, invasion and angiogenesis of the breast cancer cells by inhibiting the activation of the Wnt/ß-catenin signaling pathway.


Assuntos
Neoplasias da Mama/genética , Proteínas de Homeodomínio/genética , Neovascularização Patológica/genética , beta Catenina/genética , Adulto , Idoso , Apoptose/genética , Neoplasias da Mama/patologia , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Proteínas de Homeodomínio/antagonistas & inibidores , Humanos , Células MCF-7 , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética , Via de Sinalização Wnt/genética
20.
Cancer Med ; 7(2): 471-484, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29282893

RESUMO

In eukaryotic cells, autophagy is a process associated with programmed cell death. During this process, cytoplasmic proteins and organelles are engulfed by double-membrane autophagosomes, which then fuse with lysosomes to form autolysosomes. These autolysosomes then degrade their contents to recycle the cellular components. Autophagy has been implicated in a wide variety of physiological and pathological processes that are closely related to tumorigenesis. In recent years, an increasing number of studies have indicated that nonsteroidal anti-inflammatory drugs, such as celecoxib, meloxicam, sulindac, aspirin, sildenafil, rofecoxib, and sodium salicylate, have diverse effects in cancer that are mediated by the autophagy pathway. These nonsteroidal anti-inflammatory drugs can modulate tumor autophagy through the PI3K/Akt/mTOR, MAPK/ERK1/2, P53/DRAM, AMPK/mTOR, Bip/GRP78, CHOP/ GADD153, and HGF/MET signaling pathways and inhibit lysosome function, leading to p53-dependent G1 cell-cycle arrest. In this review, we summarize the research progress in autophagy induced by nonsteroidal anti-inflammatory drugs and the molecular mechanisms of autophagy in cancer cells to provide a reference for the potential benefits of nonsteroidal anti-inflammatory drugs in cancer chemotherapy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
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