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1.
Kaohsiung J Med Sci ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32757457

RESUMO

Cervical cancer (CC) seriously threatens the health of women. Radiation therapy (RT) is the major treatment for CC. However, the recurrent CC can acquire resistance to RT. Thus, it is necessary to find a new method for reversing RT resistance in CC. It has been reported that microRNA-324-5p (miR-324-5p) can suppress the progression of multiple cancers. However, whether it can reverse resistance to RT in CC remains unclear. qRT-PCR and Western blotting were used to detect gene and protein expression in CC cells, respectively. Cell proliferation was tested by CCK-8 assay and colony formation assay. In addition, cell apoptosis was detected by flow cytometry. Transwell assays were performed to detect cell migration. Dual luciferase reporter assay and TargetScan were used to explore the targets of miR-324-5p. MiR-324-5p was downregulated in CC cells. Overexpression of miR-324-5p sensitized CC cells to RT. In addition, miR-324-5p mimics significantly induced apoptosis and inhibits the migration of CC cells in the presence of 137 Cs ionizing radiation. Furthermore, miR-324-5p sensitized CC cells to ionizing radiation by targeting ELAV-like RNA binding protein 1 (ELAVL1). MiR-324-5p overexpression affects the radiotherapy response of CC by targeting ELAVL1, which may serve as a new target for the treatment of CC.

2.
Gynecol Minim Invasive Ther ; 9(2): 74-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676284

RESUMO

Objectives: The objective of this study is to evaluate the efficacy of autocross-linked hyaluronic acid (HA) compared with intrauterine device (IUD) for preventing intrauterine adhesions (IUAs) in infertile patients after hysteroscopic adhesiolysis. Materials and Methods: A randomized clinical trial (ChiCTR-IOR-16007746). Upon completion of adhesiolysis, 3 ml of HA gel was placed into the uterine cavity in Group A; 3 ml of HA gel and an IUD were placed in Group B; and only an IUD was placed in Group C. A second hysteroscopic examination was performed in all patients at approximately 1 month postoperatively for the evaluation of IUA. The primary outcome measure was the effective rate of IUA prevention based on the American Fertility Society (AFS) scoring system. Results: Eighty-nine women were randomly distributed into two groups for intention to treat with 30 patients in Group A, 24 patients in Group B, and 35 patients in Group C. Patients were scored and stratified into three degrees and were enrolled using the simple random sampling method. The three groups were well balanced. There were no significant differences in age, endometrial thickness, the previous number of pregnancy, and the distribution of adhesion categories across mild, moderate, and severe between the three groups. The effective rate of IUA prevention, the AFS score after therapy, and the percentage improvements of Chinese score and AFS score before and after surgery were statistically significant difference between Groups A and C. The clinical pregnancy rate in Group A was higher than those in Groups B and C, but the difference was not statistically significant. Conclusion: HA gel has an advantage over an IUD in reducing IUA recurrence and decreasing adhesions.

3.
Biosci Rep ; 39(6)2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31092700

RESUMO

BACKGROUND: Emerging evidences have indicated that long non-coding RNAs (LncRNAs) play vital roles in cancer development and progression. Previous studies have suggested that overexpression of SPRY4 intronic transcript 1 (SPRY4-IT1) predicates poor prognosis and promotes tumor progress in cervical cancer (CC). However, the underlying mechanism of SPRY4-IT1 in CC remains unknown. The aim of the present study is to evaluate the function and mechanism of SPRY4-IT1 in CC. METHODS: SPRY4-IT1 was detected by quantitative PCR. Wound-healing assay and Transwell assay were performed to detect cell migration and invasion, respectively. Western blotting assays were used to analyze the protein expression of E-cadherin, N-cadherin and vimentin. Tumor xenografts experiments were performed to detect the effect of SPRY4-IT1 in vivo. Dual luciferase reporter assay was used to investigate potential molecular mechanism of SPRY4-IT1 in CC cells. RESULTS: SPRY4-IT1 was up-regulated in CC cell lines. Knockdown of SPRY4-IT1 significantly inhibited CC cells migration and invasion in vitro and in vivo Moreover, knockdown of SPRY4-IT1 significantly suppressed the epithelial-mesenchymal transition (EMT) of CC by increased E-cadherin expression and decreased the N-cadherin and vimentin expression. Mechanically, SPRY4-IT1 could directly bind to miR-101-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-101-3p to regulate the expression of the target gene ZEB1Conclusions: Our findings indicate that the SPYR4-IT1/miR-101-3p/ZEB1 axis contributes to CC migration and invasion, which may provide novel insights into the function of lncRNA-driven tumorigenesis of CC.


Assuntos
Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Animais , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Interferência de RNA , Transdução de Sinais/genética , Carga Tumoral/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
4.
J Matern Fetal Neonatal Med ; 32(22): 3801-3805, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29727258

RESUMO

Objective: To evaluate the association between preeclampsia and three single nucleotide polymorphisms (rs13405728 in LHCGR gene; rs13429458 in THADA gene, and rs2479106 in DENND1A gene) which were identified to be genetic variants of polycystic ovary syndrome (PCOS) by genome-wide association study in Han Chinese populations. Methods: A total of 784 northern Han Chinese women (378 controls and 406 cases) were genotyped for the three genetic variants by polymerase chain reaction and direct sequencing. Unconditional logistic regression analysis was used to adjust the impact of prepregnancy body mass index, primiparas, and maternal age. Results: No significant difference was found in the allele frequencies of the three genetic variants between cases and controls (p > .05), but genotype frequency of the SNP rs2479106 was significantly differ between cases and controls when analyzed under recessive models (p = .02). There was also a substantial difference in the genotype frequencies of the SNP rs13429458 between cases and controls under additive models (p = .01). Conclusions: Genetic variants of PCOS (rs13405728 in LHCGR gene; rs13429458 in THADA gene and rs2479106 in DENND1A gene) may not be involved in the development of preeclampsia in Han Chinese women.


Assuntos
Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Receptores do LH/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/genética , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/etnologia , Gravidez , Adulto Jovem
5.
Genet Test Mol Biomarkers ; 20(8): 471-4, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27315129

RESUMO

AIMS: To evaluate the association between preeclampsia (PE) and the single nucleotide polymorphism (SNP) rs13333226, located in the promoter region of the UMOD gene. METHODS: A total of 1248 pregnant Han Chinese women (716 controls and 532 patients with PE) were included in this study. Genotyping of the rs13333226 polymorphism was performed by real-time PCR using a TaqMan-minor groove binder (MGB) probe assay. RESULTS: No significant differences were detected in the allele (p = 0.62, OR = 1.08, 95% CI = 0.81-1.44) and genotype frequencies of rs13333226 (padditive = 0.38, pdominant = 0.45, precessive = 0.31) between cases and controls. When patients were divided into subgroups, no association was found with mild preeclampsia (M PE), severe preeclampsia (S PE), early onset PE, or late-onset PE. Furthermore, no significant differences were detected in the genotype and allele frequencies of rs1333226 between patients with M PE and S PE (p > 0.05) or between patients with late and early onset of the disease (p > 0.05). CONCLUSIONS: UMOD rs13333226 does not appear to be associated with PE in Han Chinese women.


Assuntos
Pré-Eclâmpsia/genética , Uromodulina/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Grupos Étnicos/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez , Regiões Promotoras Genéticas
6.
Asian Pac J Cancer Prev ; 15(12): 4915-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24998563

RESUMO

BACKGROUND AND AIMS: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. METHODS: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/ DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. RESULTS: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. CONCLUSIONS: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.


Assuntos
Portadores de Fármacos , Terapia Genética , Vetores Genéticos/uso terapêutico , Proteínas de Fluorescência Verde/genética , Nanomedicina , Polietilenoglicóis/uso terapêutico , Neoplasias do Colo do Útero/terapia , Apoptose , Proliferação de Células , Células Cultivadas , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanopartículas , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
7.
Oncol Rep ; 31(6): 2545-54, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24700112

RESUMO

Ovarian cancer is a highly invasive and metastatic disease with poor prognosis, particularly if this disease is diagnosed at an advanced stage, which is often the case. Researchers have argued that ovarian cancer cells that have undergone epithelial­to­mesenchymal transition (EMT) acquire aggressive malignant properties; however, the relevant molecular mechanisms in this setting are poorly understood. In cancer cases, the transcription factor forkhead box protein C2 (FOXC2) has been detected, but the function of this factor in ovarian cancer tumorigenesis remains unclear. In the present study, FOXC2 was overexpressed in invasive ovarian cancer cell lines and tissues. The invasive potential of ovarian cancer cells was significantly increased by ectopic FOXC2 expression but it was significantly decreased by RNA interference targeting FOXC2. E­cadherin and vimentin expression levels were modulated by FOXC2. These results indicated that FOXC2 was required for the maintenance of the mesenchymal phenotype after TGF­ß1 induced EMT in human ovarian cancer cells. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies. These therapies can then be performed to treat invasive ovarian tumor.


Assuntos
Fatores de Transcrição Forkhead/biossíntese , Invasividade Neoplásica/genética , Neoplasias Ovarianas/genética , Fator de Crescimento Transformador beta1/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/patologia , Interferência de RNA , Fator de Crescimento Transformador beta1/metabolismo
8.
Reprod Sci ; 21(11): 1423-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24642721

RESUMO

Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Fenótipo , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/etnologia , Gravidez , Fatores de Risco , Adulto Jovem
9.
PLoS One ; 8(8): e71202, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23976997

RESUMO

BACKGROUND: Preeclampsia, characterized by hypertension and proteinuria, is a multifactorial disease caused by complex interactions between environmental and genetic factors. A recent genome-wide association study of blood pressure reported an association between hypertension and rs11646213. This study evaluated the association between preeclampsia and rs11646213. METHODS: A total of 454 cases and 460 controls were recruited to participate in this study. The single nucleotide polymorphism (SNP) rs11646213 was genotyped by polymerase chain reaction (PCR) and direct sequencing. RESULTS: The allele frequency of rs11646213 was significantly different between the preeclampsia and control groups (P = 0.017, OR = 1.36, 95% CI = 1.06-1.76). Differences were particularly significant in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17-2.03) and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16-2.13). Genotyping analysis showed that the T allele of rs11646213 could confer a risk for preeclampsia, severe preeclampsia and early-onset preeclampsia. CONCLUSIONS: Rs11646213 upstream of the CDH13 gene is associated with preeclampsia in Han Chinese women.


Assuntos
Loci Gênicos , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático , Caderinas/genética , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Pré-Eclâmpsia/etnologia , Pré-Eclâmpsia/patologia , Gravidez , Índice de Gravidade de Doença
10.
Zhonghua Fu Chan Ke Za Zhi ; 48(1): 11-5, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23531244

RESUMO

OBJECTIVE: To investigate the impact on ovarian reserve function by different hemostasis methods during laparoscopic surgery in treatment of ovarian endometrioma. METHODS: From September 2008 to February 2010, 162 cases with ovarian endometrioma undergoing laparoscopic surgery in Shandong Provincial Hospital were enrolled in this study. At the 3rd day of the menstrual cycle before surgery and the 1st, 3rd, 6th and 12th cycle after surgery, serum FSH and anti-mullerian hormone (AMH) and ultrasound basal antral follicle count (AFC) and peak systolic velocity (PSV) were examined and compared. Based on hemostasis method, those patients were divided into 3 groups, including 54 cases in bipolar hemostasis, 54 cases in ultrasonic scalpel hemostasis and suture after excision of endometrioma. RESULTS: (1) Before surgery: no significant different factors among three groups before surgery were observed, including age, size of endometrioma, the level of FSH, AMH, AFC, PSV(P > 0.05). (2) Ovarian reserve function after surgery: 1) FSH: at the 1st, 3rd, 6th and 12th month follow-up, the FSH in the bipolar group was (11.7 ± 4.0), (9.9 ± 4.0), (9.5 ± 4.3), (9.5 ± 3.9) U/L, and the FSH in ultrasonic scalpel group was (11.4 ± 4.3), (9.7 ± 4.0), (9.2 ± 3.7), (9.9 ± 4.6) U/L, were significantly higher than (9.3 ± 3.8), (6.7 ± 3.0), (6.5 ± 3.2), (6.4 ± 2.2) U/L in suture group respectively (all P < 0.05). 2) AMH: at the 1st, 3rd, 6th and 12th month follow-up, the AMH in the bipolar group was (1.8 ± 0.9), (1.8 ± 1.0), (1.9 ± 1.0), (2.0 ± 1.0) µg/L, and the AMH in the ultrasonic scalpel group was (1.6 ± 0.8), (1.8 ± 1.0), (2.0 ± 1.1), (2.1 ± 1.0) µg/L, which were significantly lower than (2.8 ± 1.7), (2.9 ± 1.6), (3.0 ± 1.3), (3.2 ± 1.5) µg/L in suture group, respectively (all P < 0.05). 3) AFC: there was no significant difference of APC among the three groups in the 1st month after surgery. However, at the 3rd, 6th and 12th month follow-up, the AFC of 4.8 ± 1.4, 5.9 ± 1.5, 6.1 ± 1.5 in the suture group was significant higher than 3.7 ± 1.4, 4.1 ± 1.4, 4.0 ± 1.5 in bipolar group and 3.6 ± 1.3, 4.0 ± 1.1, 3.9 ± 1.5 in ultrasonic group, respectively (all P < 0.05). 4) PSV: at the 1st, 3rd, 6th and 12th month follow-up, the PSV of the bipolar group (7.9 ± 3.5), (8.1 ± 3.3), (8.4 ± 3.1), (8.6 ± 3.0) cm/s in bipolar group and (8.1 ± 3.5), (8.0 ± 3.0), (7.9 ± 3.2), (8.0 ± 2.9) cm/s in ultrasonic group were significant lower than (10.9 ± 3.3), (12.0 ± 3.2), (11.8 ± 3.0), (12.1 ± 4.1) cm/s in suture group, respectively. (all P < 0.05). CONCLUSIONS: Bipolar or ultrasonic scalpel hemostasis during laparoscopic excision of ovarian endometrioma is associated with a significant reduction in ovarian reserve. Electrocoagulation of the ovarian tissue should be avoided.


Assuntos
Endometriose/cirurgia , Hemostasia Cirúrgica/métodos , Laparoscopia , Cistos Ovarianos/cirurgia , Ovário/fisiopatologia , Técnicas de Sutura , Adolescente , Adulto , Hormônio Antimülleriano/sangue , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Eletrocoagulação , Endometriose/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hemostasia Cirúrgica/instrumentação , Humanos , Cistos Ovarianos/sangue , Folículo Ovariano/citologia , Folículo Ovariano/diagnóstico por imagem , Ovário/diagnóstico por imagem , Ovário/cirurgia , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
11.
Dongwuxue Yanjiu ; 33(5): 473-80, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23019028

RESUMO

Myostatin (MSTN) is a member of the TGF-ß superfamily that acts as a negative regulator of skeletal muscle growth. A full-length, 2 180 bp, cDNA sequence of the myostatin gene from Schizopygopisis pylzovi was cloned with RT-PCR,5'-RACE and 3'-RACE and the cDNA clone included a 1 128 bp ORF, encoding a 375 amino acid peptide. Using PCR, we obtained the sequences of two introns of the MSTN gene and found that its structure in Schizopygopsis pylzovi was similar to that of other vertebrates, including three exons and two introns. Likewise, the putative MSTN peptide of Schizopygopsis pylzovi contains a conserved RXXR proteolytic cleavage domain, and 8 conserved cysteine residues in the C terminal of the protein, similar to other vertebrates. Phylogenetic analysis showed that the MSTN of Schizopygopsis pylzovi has high homology with other cyprinid fishes, but a low homology with mammals and birds. In the 9 examined tissues, the MSTN gene was highly expressed in heart, kidney, intestine and spermary, while weakly expressed in muscle, brain, fat, gill and hepatopancreas. Quantitative real-time PCR analysis showed that the expression of MSTN gene was different during embryo development, suggesting that the fish MSTN may not only play roles in muscle development but also contribute to other biological functions.


Assuntos
Clonagem Molecular , Cipriniformes/genética , Proteínas de Peixes/genética , Miostatina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Cipriniformes/classificação , Cipriniformes/metabolismo , DNA Complementar/genética , DNA Complementar/metabolismo , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Dados de Sequência Molecular , Miostatina/metabolismo , Filogenia
12.
Biochemistry ; 48(38): 9122-31, 2009 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-19691360

RESUMO

ABCG2 is a half-ATP binding cassette (ABC) drug transporter that consists of a nucleotide binding domain (NBD) followed by a transmembrane domain. This half-ABC transporter is thought to form a homodimer in the plasma membrane where it transports anticancer drugs across the biological membranes in an ATP-dependent manner. Substitution of the putative catalytic residue E211 with a nonacidic amino acid glutamine (E211Q) completely abolished its ATPase activity and ATP-dependent methotrexate transport, suggesting that ATP hydrolysis is required for the ATP-dependent solute transport. However, whether one ATP hydrolysis or two ATP hydrolyses in the homodimer of ABCG2 with the NBD.ATP.ATP.NBD sandwich structure is/are required for the ATP-dependent solute transport is not known yet. To address this question, we have made an YFP/ABCG2 fusion protein and expressed this 99 kDa fusion protein alone or along with the 70 kDa E211Q-mutated ABCG2 in BHK cells. Although membrane vesicles prepared from BHK cells expressing YFP/ABCG2 exert higher ATPase activity than that of wt ABCG2, the dATP-dependent methotrexate transport activities of these two proteins are the same. Interestingly, membrane vesicles prepared from BHK cells expressing both YFP/ABCG2 and E211Q-mutated ABCG2 (with a ratio of 1:1) form homodimers and heterodimer and exert 55% of wt ABCG2 ATPase activity that can be further enhanced by anticancer drugs, suggesting that the wt NBD in the heterodimer of YFP/ABCG2 and E211Q may be able to hydrolyze ATP. Furthermore, the membrane vesicles containing both YFP/ABCG2 and E211Q exert approximately 79% of wt ABCG2-mediated methotrexate transport activity, implying that the heterodimer harboring YFP/ABCG2 and E211Q may be able to transport the anticancer drug methotrexate across the biological membranes.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Metotrexato/farmacocinética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/química , Adenosina Trifosfatases/química , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Substituição de Aminoácidos , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Transporte Biológico Ativo/genética , Domínio Catalítico/genética , Linhagem Celular , Cricetinae , Primers do DNA/genética , Dimerização , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Técnicas In Vitro , Cinética , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mutagênese Sítio-Dirigida , Proteínas de Neoplasias/química , Estrutura Quaternária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
13.
Fertil Steril ; 92(4): 1428-1435, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18930212

RESUMO

OBJECTIVE: To investigate the impact of electrocoagulation on ovarian reserve after laparoscopic excision of ovarian cysts and the possible mechanisms. DESIGN: A prospective study. SETTING: Obstetrics and Gynecology Department of a university hospital. PATIENT(S): 191 patients with benign ovarian cysts undergoing ovarian cystectomy. INTERVENTION(S): Laparoscopic ovarian cystectomy using bipolar or ultrasonic scalpel electrocoagulation and laparotomic ovarian cystectomy using sutures after the excision of ovarian cysts. MAIN OUTCOME MEASURE(S): Follicle-stimulating hormone (FSH) assay and transvaginal ultrasound evaluating basal antral follicle number, mean ovarian diameter, and ovarian stromal blood flow velocity at day 3 of menstrual cycles 1, 3, 6, and 12 after surgery. RESULT(S): When comparing the bipolar group and ultrasonic scalpel group with the suture group, a statistically significant increase of the mean FSH value was found in bilateral-cyst patients at 1-, 3-, 6-, and 12-month follow-up evaluations and in unilateral-cyst patients at the 1-month follow-up evaluation. Statistically significant decreases of basal antral follicle number and mean ovarian diameter were found during the 3-, 6-, 12-month follow-up evaluations as well as statistically significant decreases of peak systolic velocity at all of the follow-up evaluations. CONCLUSION(S): Electrocoagulation after laparoscopic excision of ovarian cysts is associated with a statistically significant reduction in ovarian reserve, which is partly a consequence of the damage to the ovarian vascular system.


Assuntos
Eletrocoagulação , Laparoscopia , Cistos Ovarianos/cirurgia , Folículo Ovariano/patologia , Adolescente , Adulto , Contagem de Células , Eletrocoagulação/efeitos adversos , Eletrocoagulação/métodos , Feminino , Fertilidade/fisiologia , Hormônio Foliculoestimulante/sangue , Seguimentos , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/etiologia , Infertilidade Feminina/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Cistos Ovarianos/diagnóstico por imagem , Cistos Ovarianos/patologia , Cistos Ovarianos/reabilitação , Prognóstico , Resultado do Tratamento , Ultrassonografia , Vagina/diagnóstico por imagem , Adulto Jovem
14.
Chin Med J (Engl) ; 121(2): 166-71, 2008 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-18272045

RESUMO

BACKGROUND: Rosiglitazone is known as the most potent and specific peroxisome proliferators-activated receptor gamma (PPAR-gamma) ligand. It has potentially far-reaching effects on pathophysiological processes, from cancer to atherosclerosis and diabetes. However, it is not clear whether rosiglitazone affects the protein expression of transforming growth factor beta3 (TGF-beta3) and the cell proliferation in human uterine leiomyoma cells in vitro. METHODS: Human uterine leiomyoma tissues were dissected and cultured. Cells were divided into 5 groups: one control group and other four groups with different concentrations of rosiglitazone (10(-7), 10(-8), 10(-9) and 10(-10) mol/L). Cells were cultured for 72 hours in serum-free Dulbecco's modified Eagle's medium. MTT reduction assay was used to detect the cell proliferation. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of PPAR-gamma and TGF-beta3. Immunofluorescence staining was used to detect the expressions of PPAR-gamma and TGF-beta3 proteins. RESULTS: MTT reduction assay indicated that the treatment with rosiglitazone (from 10(-7) to 10(-9) mol/L) resulted in an inhibition of the cell growths after 72 hours (P < 0.01). RT-PCR analysis revealed that 10(-7) mol/L rosiglitazone significantly affected the gene expression at 72-hour: PPAR-gamma mRNA expression was up-regulated and TGF-beta3 mRNA was down-regulated and rosiglitazone at the concentration of 10(-7) mol/L affected these most effectively (P < 0.01). Immunofluorescence staining demonstrated that treatment with 10(-7) mol/L rosiglitazone resulted in the significant changes of PPAR-gamma and TGF-beta3 protein expressions compared with the other treatment groups and the control group at 72-hour (P < 0.01). All the effects of rosiglitazone on uterine leiomyoma cells were dose- and time-dependent in vitro. CONCLUSIONS: The present study demonstrates that the PPAR-gamma activator, rosiglitazone, inhibits the cell proliferation partly through the regulations of PPAR-gamma and TGF-beta3 expressions. The cross-talk between the signal pathways of PPAR-gamma and TGF-beta3 may be involved in the process.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Leiomioma/tratamento farmacológico , PPAR gama/agonistas , Tiazolidinedionas/farmacologia , Fator de Crescimento Transformador beta3/genética , Neoplasias Uterinas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Leiomioma/patologia , PPAR gama/análise , PPAR gama/genética , RNA Mensageiro/análise , Rosiglitazona , Fator de Crescimento Transformador beta3/análise , Neoplasias Uterinas/patologia
15.
Zhonghua Fu Chan Ke Za Zhi ; 38(9): 552-5, 2003 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-14680611

RESUMO

OBJECTIVE: To investigate the effect of high dose mifepristone and high dose progesterone in the treatment of patients with endometrial carcinoma and to explore the possible mechanisms associating with them. METHODS: Thirty untreated patients diagnosed as endometrial carcinoma through dilation and curettage of the uteri were divided into 3 groups at random. Each group was given medroxyprogesterone acetate (MPA), (500 mg/day) or mifepristone (MIF), (100 mg/day) or MIF (100 mg/day) + MPA (500 mg/day) for 5 days respectively. On the sixth day, hysterectomy was performed on these patients. The endometrial cancer specimen of post-hysterectomy was compared with the one of pre-administrating. The morphologic changes of the endometrial cancer cells were observed through light microscope. Immunohistochemistry assay (SP method) was applied to determine the localization and immunoreactive intensity of proliferating cell nuclear antigen (PCNA), estrogen receptor (ER), progesterone receptor (PR), B-cell leukemia lymphoma-2 (bcl-2), bcl-2 associated X protein (bax) and CD(44v6). RESULTS: Better differentiation degree and active excretion were observed in all of the post-hysterectomy endometrial specimen. In the same time, apoptosis of carcinoma cells was observed. The most significant changes were seen in the MIF + MPA group. In the MPA group, the pre-treatment and post-treatment expression of PR (2.9 +/- 1.1, 1.6 +/- 0.8), ER (2.8 +/- 0.9, 1.4 +/- 0.9), PCNA (0.84 +/- 0.10, 0.60 +/- 0.12), bcl-2 (0.236 +/- 0.089, 0.157 +/- 0.981) and CD(44v6) (4.6 +/- 1.8, 2.5 +/- 1.9) were all decreased (all P < 0.01); the expression of bax (0.20 +/- 0.10, 0.42 +/- 0.07) was increased (P < 0.01). In the MIF group, the expression of PR (3.4 +/- 1.0, 1.9 +/- 0.8), ER (2.7 +/- 0.9, 1.2 +/- 0.7), PCNA (0.80 +/- 0.15, 0.65 +/- 0.10), bcl-2 (0.214 +/- 0.097, 0.121 +/- 0.073) were all decreased (all P < 0.01); the expression of bax (0.21 +/- 0.05, 0.44 +/- 0.09) was increased (P < 0.01); no significant change in the expression of CD(44v6) (4.2 +/- 2.0, 4.3 +/- 1.7) was seen (P > 0.05). In the MIF + MPA group, the expression of PR (3.2 +/- 1.0, 0.8 +/- 0.8), ER (2.7 +/- 0.9, 0.7 +/- 0.9), PCNA (0.81 +/- 0.09, 0.25 +/- 0.09), bcl-2 (0.225 +/- 0.091, 0.066 +/- 0.009) and CD(44v6) (4.5 +/- 1.9, 2.7 +/- 1.6) were all decreased (all P < 0.01); the expression of bax (0.22 +/- 0.06, 0.59 +/- 0.09) was increased (P < 0.01); there were significant different expression of PCNA, ER, PR, bax and bcl-2 as compared with the MIF group and the MPA group, respectively (all P < 0.01). The expression of CD(44v6) was significantly different (P < 0.01) between the MIF + MPA group, and the MIF group, but not significantly different between the MIF + MPA group and the MPA group. CONCLUSIONS: The study indicates that high dose progesterone could inhibit the growth, promote apoptosis and inhibit metastasis of endometrial carcinoma, MIF could inhibit the growth and promote apoptosis, MIF + MPA could more strongly inhibit the growth, promote apoptosis and inhibit metastasis of endometrial carcinoma than MIF or MPA, and synergistic effect was observed on the expression of PCNA, ER, PR, bax and bcl-2.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Mifepristona/administração & dosagem , Progesterona/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Neoplasias do Endométrio/química , Neoplasias do Endométrio/patologia , Feminino , Glicoproteínas/análise , Humanos , Receptores de Hialuronatos/análise , Pessoa de Meia-Idade , Antígeno Nuclear de Célula em Proliferação/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise
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