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1.
Skeletal Radiol ; 53(4): 697-707, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37843585

RESUMO

OBJECTIVE: To perform a meta-analysis comparing the MRI features of tuberculous and pyogenic spondylitis, using histopathological results and/or blood culture as the standard reference. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for English-language studies on the MRI features of tuberculous and pyogenic spondylitis published between January 2010 and February 2023. Risk for bias and concerns regarding applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled MRI features' proportions were calculated using a bivariate random-effects model. RESULTS: Thirty-two studies met the inclusion criteria: 21 for tuberculous spondylitis, three for pyogenic spondylitis, and eight for both. Of the nine informative MRI features comparing tuberculous spondylitis to pyogenic spondylitis, involvement of ≥ 2 vertebral bodies (92% vs. 88%, P = .004), epidural extension (77% vs. 25%, P < .001), paravertebral collection (91% vs. 84%, P < .001), subligamentous spread (93% vs. 24%, P < .001), thin and regular abscess wall (94% vs. 18%, P < .001), vertebral collapse (68% vs. 24%, P < .001), and kyphosis (39% vs. 3%, P < .01) were more suggestive of tuberculous spondylitis, while disc signal change (82% vs. 95%, P < .001) and disc height loss (22% vs. 59%, P < .001) were more suggestive of pyogenic spondylitis. CONCLUSION: Involvement of ≥ 2 vertebral vertebral bodies, soft tissue attribution, thin and regular abscess wall, vertebral collapse, and kyphosis were MRI features more common in tuberculous spondylitis, while disc signal change and height loss were more common in pyogenic spondylitis.


Assuntos
Cifose , Espondilartrite , Espondilite , Tuberculose da Coluna Vertebral , Humanos , Abscesso , Estudos Retrospectivos , Espondilite/diagnóstico por imagem , Espondilite/patologia , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/patologia , Imageamento por Ressonância Magnética/métodos
2.
BMC Surg ; 23(1): 325, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875825

RESUMO

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been recently used for the assessment of cervical lymph node metastasis (LNM) to guide surgical operation in patients with papillary thyroid carcinoma (PTC). However, the specificity and sensitivity of CEUS reported from previous studies are not consistent. The objective of this study was to evaluate the diagnostic value of CEUS for the metastasis of cervical lymph nodes in PTC patients based on data from one regional central hospital. METHODS: The diagnostic value of CEUS in preoperative LNM of PTC patients was concluded by comparing the results of CEUS on lymph node status with postoperative pathology examination. In addition, this study conducted hierarchical analysis of PTC patients to explore whether tumor size, different lymph node regions, and Hashimoto's thyroiditis influence the assessment of CEUS. RESULTS: This research study ultimately enrolled 965 PTC patients, including 266 males and 699 females with a mean age of 42.27 ± 11.34 years. A total of 527 patients were considered clinical-node negative, and 438 were clinical-node positive before surgery. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the assessment of LNM in PTC patients were 56.00%, 71.00%, 57.06%, 69.76% and 62.59%, respectively. For central and lateral lymph nodes, the accuracy of CEUS in PTC patients was 49.43% and 54.30%, respectively. In addition, it was shown that the accuracy of CEUS in PTC patients with Hashimoto's thyroiditis (HT) slightly decreased to 58.44%, and the accuracy of CEUS in PTC patients with non-HT in turn increased to 64.17%. The accuracy of CEUS in non-papillary thyroid microcarcinoma (PTMC) and PTMC patients was 65.68% and 61.24%, respectively. The accuracy of CEUS in predicting central LNM was significantly different between PTC patients with or without HT (P < 0.001) in this study but not for lateral lymph nodes (P = 0.114). CONCLUSION: The accuracy of CEUS in the assessment of LNM in PTC is not consistently satisfactory, especially for central lymph nodes, small tumor diameters, or patients with HT. More diagnostic technologies for abnormal lymph nodes should be considered in PTC patients.


Assuntos
Doença de Hashimoto , Neoplasias da Glândula Tireoide , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Estudos Retrospectivos , Metástase Linfática/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Ultrassonografia/métodos , Doença de Hashimoto/patologia
3.
Med Sci Monit ; 28: e935634, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35314667

RESUMO

BACKGROUND This study aimed to compare the effectiveness of endometrial receptivity analysis (ERA)-guided personalized embryo transfer (pET) with conventional frozen embryo transfer (FET) in 281 Chinese women with recurrent implantation failure (RIF). MATERIAL AND METHODS A total of 281 eligible patients with RIF were recruited and assigned to ERA (ERA followed by pET) and FET groups. The clinical pregnancy outcomes were compared between the 2 groups. RESULTS There were no significant differences between the ERA and FET groups in terms of endometrial thickness on the day of embryo transfer, mean attempts of assisted reproductive technology (ART) treatment, anti-Mullerian hormone, follicle-stimulating hormone, or antral follicle count in the fresh cycle (P>0.05). The ERA test identified 35% of samples as receptive and 65% as nonreceptive, and comparable pregnancy outcomes were observed between receptive and nonreceptive patients (P>0.05). Higher pregnancy and implantation rates were found in the ERA group than in the FET group (P<0.01), while no significant differences were detected between the 2 groups in terms of miscarriage rates (P>0.05). CONCLUSIONS In this study of Chinese women with RIF undergoing in vitro fertilization and embryo transfer, ERA-guided pET resulted in a significant improvement in pregnancy and implantation rates when compared with FET.


Assuntos
Infertilidade Feminina , China , Implantação do Embrião , Transferência Embrionária/métodos , Endométrio , Feminino , Humanos , Infertilidade Feminina/terapia , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
4.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4875-4881, 2020 Oct.
Artigo em Zh | MEDLINE | ID: mdl-33350259

RESUMO

3-Hydroxy-3-methylglutaryl coenzyme A reductase(HMGR) is the first rate-limiting enzyme in the mevalonic acid(MVA)pathway and it is an important regulatory site in the metabolism of terpenoids in the cytoplasm. In this study, Siraitia grosvenorii that had been pollinated 0 day,1 day,3 days,15 days and 30 days were used as experimental materials. Based on the transcriptome data, two HMGR genes were cloned from S. grosvenorii cDNA and named SgHMGR2(GenBank Accession Numbers MT270447) and SgHMGR3(GenBank Accession Number MT270448). The two genes contain open reading frames(ORFs) of 1 746 bp and 1 782 bp, encoding 582 and 594 amino acids, and their molecular masses are estimated to be 62.7,63.2 kDa, respectively. Isoelectric point are 8.34 and 7.47, both of which do not contain signal peptides, are non-secretory proteins, and have two transmembrane structures. Combining the conserved regions of the proteins and the analysis of the evolutionary tree, it was confirmed that the genes are indeed HMGR family genes. Real-time PCR was used to detect the expression pattern of SgHMGRs at different times after pollination, and the highest expression level was 15 days after pollination. Finally, two full-length SgHMGRs were cloned from S. grosvenorii for the first time, and the differential expression of SgHMGRs at different times after pollination was revealed, providing a research basis for the mining of key enzyme gene elements in the biosynthesis pathway of S. grosvenorii terpenoids.


Assuntos
Cucurbitaceae , Hidroximetilglutaril-CoA Redutases , Sequência de Aminoácidos , Clonagem Molecular , Coenzima A , Cucurbitaceae/genética , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Filogenia
5.
Respir Res ; 20(1): 106, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142317

RESUMO

BACKGROUND: Tumor chemo-resistance is a hallmark of malignant tumors as well as the major cause of poor survival rates in lung cancer. Transmembrane-4 L-six family member-1 (TM4SF1), an antigen that serves as an oncogene, mainly affects tumor invasion and metastasis. We investigated the roles of TM4SF1 in non-small-cell lung cancer progression, particularly in the regulation of chemo-sensitivity. METHODS: TM4SF1 was silenced by small interfering RNA transfection.TM4SF1 expression in cell lines and tissues were determined by Quantitative Real-time PCR. MTS, clonogenic, Transwell assay, Flow cytometry verified cell function. By RT-PCR, Western blot, the mechanisms were studied. RESULTS: TM4SF1 was upregulated in both lung cancer cell lines and tissues, compared with 293 T epithelial cells. Analysis of online databases revealed that high expression of TM4SF1 is associated with the older patient age, smoking habits, and poor patient survival and outcome. Knockdown of TM4SF1 substantially inhibited tumor cell growth, migration, and invasion, and enhanced the chemo-sensitivity of the lung cancer cell lines A549 and H1299 to cisplatin and paclitaxel. Furthermore, the silencing of TM4SF1 induced lung cancer cell apoptosis and arrested cells at the G2/M phase. These results suggest that TM4SF1 is associated with lung cancer progression and appears to be required for tumor cell growth, maintenance of chemo-resistance and metastasis. We further found that TM4SF1 exerts these effects in part by regulating the expression of the discoidin domain receptor DDR1 and its downstream target, the Akt/ERK/mTOR pathway, and consequently alters cell sensitivity to chemo-reagents and contributes to invasion and metastasis. CONCLUSIONS: These findings demonstrate that TM4SF1 may serve as a prognostic factor for lung cancer chemo-response and patient outcome.


Assuntos
Antígenos de Superfície/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptor com Domínio Discoidina 1/metabolismo , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas de Neoplasias/biossíntese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Células A549 , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Células HEK293 , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia
6.
J Gastroenterol Hepatol ; 34(12): 2196-2205, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30995348

RESUMO

BACKGROUND AND AIM: The high mortality and poor prognosis of hepatocellular carcinoma (HCC) have raised the public attention. Gene therapy is considered as a promising treatment option for cancer; thus, finding a new therapeutic target for HCC is urgently needed. GATA4 is a tumor suppressor gene in multiple cancers, but its role in HCC is unclear. In this study, we explored the function of GATA4 in HCC. METHODS: Reverse transcription-polymerase chain reaction and quantitative polymerase chain reaction were used to detect the mRNA expression of GATA4 in HCC cells and tissues. Cell viability, transwell, colony formation, and flow cytometry assays were applied to examine different aspects of biological effects of GATA4 in vitro. Xenografts, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assays were performed to evaluate the effect of GATA4 on tumorigenicity in vivo. Western blotting, immunofluorescence, and ß-galactosidase staining were used to investigate the mechanism underlying the function of GATA4. RESULTS: We found that GATA4 was silenced in 15/19 (79%) HCC tissues. Restoring the expression of GATA4 induced G0 /G1 phase arrest, promoted apoptosis, suppressed HCC proliferation in vitro, and inhibited HCC tumor growth in vivo. Our data further showed that the ectopic expression of GATA4 induced cellular senescence through regulating nuclear factor-κB and inducing mesenchymal-to-epithelial transition. CONCLUSIONS: Our data demonstrated that by inducing cellular senescence and mesenchymal-to-epithelial transition, GATA4 plays a crucial role as a tumor suppressor in HCC. It may thus be a potential cancer therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Senescência Celular/fisiologia , Fator de Transcrição GATA4/fisiologia , Neoplasias Hepáticas/patologia , Animais , Apoptose/genética , Apoptose/fisiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Senescência Celular/genética , Regulação para Baixo/fisiologia , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Fator de Transcrição GATA4/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Inativação Gênica , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Nus , NF-kappa B/fisiologia , Invasividade Neoplásica , Transplante de Neoplasias , RNA Mensageiro/genética , RNA Neoplásico/genética , Transdução de Sinais/fisiologia , Células Tumorais Cultivadas
7.
Biochem Biophys Res Commun ; 497(1): 187-193, 2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29428729

RESUMO

CDKN1C, also known as p57kip2, is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer. Low expression of CDKN1C was significantly associated with poor overall survival (OS) in the TCGA cohort and validated cohort composed of 1402 patients. Multivariate Cox regression analysis indicated that CDKN1C was an independent prognostic factor for worse OS (HR = 1.78, 95% CI: 1.09-2.89, p = 0.020). Furthermore, gene set enrichment analysis (GSEA) revealed that CDKN1C was significantly correlated with gene signatures involving DNA repair, cell cycle, glycolysis, adipogenesis, and two critical signaling pathways mTORC1 and PI3K/Akt/mTOR. In conclusion, our data suggested an essential role of CDKN1C in the tumorgenesis of breast cancer. Targeting CDKN1C may be a promising strategy for anticancer therapeutics.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinogênese/metabolismo , Carcinogênese/patologia , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , China/epidemiologia , Regulação para Baixo , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
8.
Biochem Biophys Res Commun ; 506(3): 685-691, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376993

RESUMO

BACKGROUND: Aberrant expression of interferon regulatory factor 4 (IRF4) has been reported in several hematologic malignancies. However, the prognostic significance of IRF4 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. METHODS: IRF4 protein expression in ESCC tumor specimens was determined immunohistochemically. The correlation of IRF4 expression with clinico-pathological features was assessed from a cohort of 100 patients with primary ESCC. Kaplan-Meier and Cox proportional regression analyses were used to evaluate the association between IRF4 expression and patient survival. RESULTS: A Kaplan-Meier analysis indicated that patients with high IRF4 expression had a significantly longer overall survival rate than those with low IRF4 expression (p = 0.0006). Furthermore, multi-variate analyses revealed that IRF4 protein expression is an independent prognostic indicator for ESCC patients. CONCLUSION: Our results suggest that increased IRF4 protein expression correlates with improved outcome in ESCC. IRF4 may therefore represent a promising prognostic biomarker and potential immuno-therapeutic target for patients with ESCC.


Assuntos
Carcinoma de Células Escamosas do Esôfago/metabolismo , Fatores Reguladores de Interferon/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico
10.
Cell Physiol Biochem ; 41(5): 1709-1724, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28365691

RESUMO

BACKGROUND/AIMS: Aberrant activation of the Wnt/ß-catenin signaling pathway plays a key role in the pathogenesis of multiple tumors including digestive cancers. Recent studies have reported that Dickkopf-related protein 2 (DKK2) is epigenetically inactivated in numerous types of cancers and that its gene products exhibit tumor-suppressive properties. However, the biological functions and underlying molecular mechanisms of DKK2 in colon carcinoma remains obscure. METHODS: We examined the expression of DKK2 in colon tumor cell lines by RT-PCR and its promoter methylation status in colon tumor cell lines and primary tumors by methylation-specific PCR (MSP). Ectopic expression of DKK2 was measured by RT-PCR prior to the other experiments. To investigate the function of DKK2, we assayed colony formation and cell proliferation, utilized flow cytometric analyses of the cell cycle and acridine orange/ethidium bromide (AO/EB) fluorescence staining for apoptosis, and examined wound healing, transwell migration and tumor growth in vivo. Western blots were used to explore the mechanisms of DKK2 in epithelial- mesenchymal transition and canonical Wnt/ß-catenin signaling. RESULTS: We show here that downregulation or silencing of DKK2 was closely associated with the hypermethylation status of its promoter and that DKK2 expression could be restored by demethylation treatment. Methylation of the DKK2 promoter was detected in nearly all tumors and tumor-adjacent tissues, but not in normal colon tissues. Ectopic expression of DKK2 in colon cell lines HCT116 and HT-29 inhibited colony formation and cell viability by inducing cell cycle G0/G1 arrest and apoptosis, and growth of stable DKK2-infected HCT116 cells in nude mice was decreased compared to controls. Furthermore, DKK2 restrained cell migration through partial reversal of epithelial-to- mesenchymal transition and also by downregulating several stem cell markers. Our data further showed that restoration of DKK2 expression resulted in downregulation of active ß-catenin and its downstream target genes. CONCLUSION: DKK2 appears to be a functional tumor suppressor regulating tumorigenesis of colorectal cancer by antagonizing Wnt/ß-catenin signaling.


Assuntos
Neoplasias Colorretais/metabolismo , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Proteínas de Neoplasias/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Proteínas de Neoplasias/genética , beta Catenina/genética
11.
J Cell Mol Med ; 20(5): 842-54, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26843424

RESUMO

Recent studies suggest that paired box 5 (PAX5) is down-regulated in multiple tumours through its promoter methylation. However, the role of PAX5 in non-small cell lung cancer (NSCLC) pathogenesis remains unclear. The aim of this study is to examine PAX5 expression, its methylation status, biological functions and related molecular mechanism in NSCLC. We found that PAX5 was widely expressed in normal adult tissues but silenced or down-regulated in 88% (7/8) of NSCLC cell lines. PAX5 expression level was significantly lower in NSCLC than that in adjacent non-cancerous tissues (P = 0.0201). PAX5 down-regulation was closely associated with its promoter hypermethylation status and PAX5 expression could be restored by demethylation treatment. Frequent PAX5 promoter methylation in primary tumours (70%) was correlated with lung tumour histological types (P = 0.006). Ectopic expression of PAX5 in silenced lung cancer cell lines (A549 and H1975) inhibited their colony formation and cell viability, arrested cell cycle at G2 phase and suppressed cell migration/invasion as well as tumorigenicity in nude mice. Restoration of PAX5 expression resulted in the down-regulation of ß-catenin and up-regulation of tissue inhibitors of metalloproteinase 2, GADD45G in lung tumour cells. In summary, PAX5 was found to be an epigenetically inactivated tumour suppressor that inhibits NSCLC cell proliferation and metastasis, through down-regulating the ß-catenin pathway and up-regulating GADD45G expression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Fator de Transcrição PAX5/metabolismo , beta Catenina/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Metilação de DNA , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Fator de Transcrição PAX5/genética , Regiões Promotoras Genéticas , Ligação Proteica , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética
12.
Exp Cell Res ; 332(2): 179-89, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25655282

RESUMO

Our previous study showed that PLCD1 significantly decreases cell proliferation and affects cell cycle progression in breast cancer cells. In the present study, we aimed to investigate its functional and molecular mechanisms, and whether or not can become a new target for gene therapies. We found reduced PLCD1 protein expression in breast tumor tissues compared with paired surgical margin tissues. PLCD1 promoter CpG methylation was detected in 55 of 96 (57%) primary breast tumors, but not in surgical-margin tissues and normal breast tissues. Ectopic expression of PLCD1 inhibited breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization proteins including RhoA and phospho-cofilin. Furthermore, we found that PLCD1 induced p53 accumulation, increased p27 and p21 protein levels, and cleaved PARP. Finally, we constructed an adenoviral vector expressing PLCD1 (AdH5-PLCD1), which exhibited strong cytotoxicity in breast cancer cells. Our findings provide insights into the development of PLCD1 gene therapies for breast cancer and perhaps, other human cancers.


Assuntos
Neoplasias da Mama/enzimologia , Metilação de DNA , Terapia Genética , Fosfolipase C delta/genética , Adenoviridae/genética , Adulto , Animais , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Forma Celular , Citoesqueleto/metabolismo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Fosfolipase C delta/metabolismo , Regiões Promotoras Genéticas , Carga Tumoral
13.
Mol Cancer Res ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949521

RESUMO

Because of its insensitivity to existing radiotherapy, namely chemotherapy and targeted treatments, triple-negative breast cancer (TNBC) remains a great challenge to overcome. Increasing evidence has indicated abnormal Wnt/ß-catenin pathway activation in TNBC but not luminal or HER2+ breast cancer, and lncRNAs play a key role in a variety of cancers. Through lncRNA microarray profiling between activated and inactivated wnt/ß-catenin pathway of TNBC tissues, lnc-WAL (wnt/ß-catenin associated lncRNA; WAL) was selected as the top upregulated lncRNA in wnt/ß-catenin pathway activation compared with the inactivation group. RIP-seq was used to compare the ß-catenin and IgG groups, where lnc-WAL could interact with ß-catenin. Clinically, increased lnc-WAL in TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted EMT, the proliferation, migration and invasion of breast cancer stem cells (BCSCs), and TNBC cells. Mechanistically, lnc-WAL inhibited ß-catenin protein degradation via Axin-mediated phosphorylation at serine 45. Subsequently, ß-catenin accumulated in the nucleus and activated the target genes. Importantly, wnt/ß-catenin pathway activation stimulated the transcription of lnc-WAL. These results pointed to a master regulatory role of lnc-WAL/Axin/ß-catenin in the malignant progression of TNBC. Our findings provide important clinical translational evidence that lnc-WAL may be a potential therapeutic target against TNBC. Implications: The positive feedback between lnc-WAL and the Wnt/ß-catenin pathway promotes TNBC progression, and lnc-WAL could be a potential prognostic marker for TNBC patients.

14.
J Control Release ; 372: 874-884, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38977133

RESUMO

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin ß1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

15.
J Cell Mol Med ; 17(10): 1236-46, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23890219

RESUMO

Dickkopf-related protein 3 (DKK3) is an antagonist of Wnt ligand activity. Reduced DKK3 expression has been reported in various types of cancers, but its functions and related molecular mechanisms in breast tumorigenesis remain unclear. We examined the expression and promoter methylation of DKK3 in 10 breast cancer cell lines, 96 primary breast tumours, 43 paired surgical margin tissues and 16 normal breast tissues. DKK3 was frequently silenced in breast cell lines (5/10) by promoter methylation, compared with human normal mammary epithelial cells and tissues. DKK3 methylation was detected in 78% of breast tumour samples, whereas only rarely methylated in normal breast and surgical margin tissues, suggesting tumour-specific methylation of DKK3 in breast cancer. Ectopic expression of DKK3 suppressed cell colony formation through inducing G0/G1 cell cycle arrest and apoptosis of breast tumour cells. DKK3 also induced changes of cell morphology, and inhibited breast tumour cell migration through reversing epithelial-mesenchymal transition (EMT) and down-regulating stem cell markers. DKK3 inhibited canonical Wnt/ß-catenin signalling through mediating ß-catenin translocation from nucleus to cytoplasm and membrane, along with reduced active-ß-catenin, further activating non-canonical JNK signalling. Thus, our findings demonstrate that DKK3 could function as a tumour suppressor through inducing apoptosis and regulating Wnt signalling during breast tumorigenesis.


Assuntos
Apoptose/fisiologia , Neoplasias da Mama/patologia , Epigênese Genética , Inativação Gênica , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Transdução de Sinais , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Bases , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Quimiocinas , Metilação de DNA , Primers do DNA , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas
16.
Signal Transduct Target Ther ; 8(1): 41, 2023 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681678

RESUMO

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones.


Assuntos
Cálculos Renais , Urolitíase , Animais , Ratos , Ácido Succínico/uso terapêutico , Osteogênese , Urolitíase/metabolismo , Cálculos Renais/tratamento farmacológico , Cálculos Renais/genética , Cálculos Renais/química , Succinatos/uso terapêutico
17.
Bioelectrochemistry ; 148: 108272, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183562

RESUMO

The dual-signal radiometric sensor can effectively reduce the difference between repeated detection and achieve higher accuracy, sensitivity and repeatability detection. In this work, we constructed a simple ratiometric electrochemical aptasensor based on functionalized ZIF-67 and ZIF-90 for sensitive detection of human epidermal growth factor receptor-2 (HER2). ZIF-67@Ferrocene (Fc)/antimonate nano flakes (AMNFs) as the capture probe has a large specific surface area and good conductivity, and have a strong adsorption capacity for aptamer single-stranded deoxyribonucleic acid (ssDNA). When the biomarker - HER2 interacts with aptamer ssDNA, it is easily desorbed from its surface. At the same time, ZIF-90@ methylene blue (MB) as the signal probe realizes one-step encapsulation of MB signal, which can avoid interference from external environment. When the target-HER2 exists, it is recognized by the capture probe, which leads to the decrease of the conductivity of the electrode. Under the action of the signal probe, the conductivity of the signal is recovered and the detection signal is amplified significantly. The designed ratiometric electrochemical aptasensor showed a wide linear range (0.5-1000 pg mL-1) and a low detection limit (155 fg mL-1) for HER2. Subsequently, it was applied to actual serum samples and showed acceptable applicability. It shows great potential for clinical screening and immediate detection of cancer biomarkers.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA , Técnicas Eletroquímicas , Ouro , Humanos , Limite de Detecção , Metalocenos , Azul de Metileno
18.
Am J Reprod Immunol ; 87(3): e13513, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34766396

RESUMO

PROBLEM: The clinical value of endometrial receptivity array (ERA), endometrial immune profiling, or a combination of both for multiple implantation failure patients is unclear. METHOD OF STUDY: One hundred and seventy-two women with a history of at least two or more consecutive implantation failures in IVF/ICSI treatment were included. According to patients' willingness, they were divided into four groups, 'no treatment', 'Immune Profiling', 'ERA' and 'ERA + Immune Profiling'. Endometrial biopsy was examined by ERA, immune profiling alone, or combination, and intention was adopted accordingly. Pregnancy outcomes were compared, and the association between ERA phases and endometrial immune profiling was also assessed. RESULTS: The overall incidence rate of the displaced window of implantation (WOI) and endometrial immune dysregulations were 84.9% and 75.3%, respectively. Implantation rate was significantly higher in the 'ERA + Immune Profiling' group than the 'no treatment' group (P = .007). Clinical pregnancy rate was somewhat improved in the three treatment groups but with a borderline significance (P = .071). After controlling for other confounders, 'ERA + Immune Profiling' treatment was associated with a higher pregnancy rate [aOR (95%CI)  = â€Š3.412 (1.387-8.395), P = .008]. There was no association between endometrial immune profiling and ERA phases. CONCLUSIONS: Our findings highlight the high incidence of displaced WOI and endometrial immune dysregulation in multiple implantation failure patients. The combination of ERA and endometrial immune profiling is more likely to have clinical value than ERA or immune profiling alone. These data suggested the unsubstitutability of ERA and endometrial immune profiling on the treatment outcome for multiple implantation failure patients.


Assuntos
Transferência Embrionária , Infertilidade Feminina , Implantação do Embrião , Transferência Embrionária/métodos , Endométrio/patologia , Feminino , Fertilização in vitro/métodos , Humanos , Infertilidade Feminina/patologia , Infertilidade Feminina/terapia , Gravidez , Taxa de Gravidez
19.
Acad Radiol ; 29(2): 317-325, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33153866

RESUMO

OBJECTIVES: We performed a meta-analysis of studies examining the computed tomography (CT) features of adnexal torsion (AT). METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies involving the proportion of CT features in patients with AT and that used surgery as the reference test. Study quality was assessed using the Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality tool. RESULTS: Twelve articles involving 483 patients were included. The pooled proportion of right-sided adnexal lesion was 54% (95% confidence interval [CI]: 49%-56%). The pooled proportions of the ovarian lesion histopathological types were: benign germ cell tumors, 33% (95% CI: 28%-37%); benign cystic lesions, 26% (95% CI: 21%-30%); benign epithelial neoplasms, 24% (95% CI: 20%-29%); sex cord-stromal tumors, 4% (95% CI: 2%-6%); borderline neoplasms, 3% (95% CI: 1%-6%); and hemorrhagic cysts, 2% (95% CI: 0%-3%). The pooled proportions of CT features were: Adnexal enlargement, 99% (95% CI: 98%-99%); adnexal with mass, 98% (95% CI: 97%-100%); twisted pedicle, 81% (95% CI: 78%-83%); mass with thickened wall, 77% (95% CI: 73%-81%); tubal thickening, 73% (95% CI: 68%-77%); abnormal location of adnexa, 69% (95% CI: 63%-75%), pelvic ascites, 43% (95% CI: 38%-49%); pelvic fat infiltration, 41% (95% CI: 34%-48%); uterine deviation, 37% (95% CI: 31%-42%); and lack of enhancement, 20% (95% CI: 14%-25%). CONCLUSION: Adnexal enlargement, adnexal mass, and twisted pedicle may be the most important CT features for diagnosing AT.


Assuntos
Doenças dos Anexos , Torção Ovariana , Doenças dos Anexos/diagnóstico por imagem , Feminino , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Anormalidade Torcional/diagnóstico por imagem
20.
J Ethnobiol Ethnomed ; 17(1): 46, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301287

RESUMO

BACKGROUND: Douyu Village, inhabited by the Lhoba people, is situated within the Eastern Himalayas, in southeastern Tibet, China. The village is located among high mountains and valleys, which feature complex terrain with cold and dry climates and distinctive vegetation types and species. The Lhoba people in this village are isolated from other groups in China. The Lhoba people have lived in this village since the 15th century and mainly depended on gathering, hunting, and swidden agriculture before the 1960s. Because they have a long history and live under extreme climatic, geographical, and ecological conditions, the Lhoba people in Douyu Village may have unique traditional knowledge about wild plants. Thus, this research aims to record the traditional botanical knowledge of the Lhoba people in Douyu. METHODS: An ethnobotanical study was conducted on the Lhoba people in Douyu Village in Longzi County, Tibet, China. Semi-structured interviews and group discussions with informed consent were used in the study. We interviewed 41 informants (14 key informants) between 18 and 75 years of age. All information was collected, organized, and compiled into "use reports" for quantitative analysis. The informant consensus factor (ICF) was used to determine the homogeneity of the informants' knowledge of medicinal plants, while the cultural importance index (CI) was used to estimate the cultural importance of shared species. RESULTS: A total of 91 wild species (90 vascular plants and 1 fungus) belonging to 71 genera and 39 families utilized by the Lhoba people in Douyu were documented. Of these species, Pimpinella xizangense and Wikstroemia lungtzeensis are endemic to Longzi County, while Sinopodophyllum hexandrum and Paeonia ludlowii are endangered species in China. All habitats, from the field vegetation at the valley bottoms to the alpine shrubland and meadows, were used for plant collection, and the numbers of species of plants collected from the various vegetation types (except for fields) decreased with increasing altitude. Our study found that 55 species are edible plants and fungi, 29 species are medicinal plants, and 38 species are used for other purposes. Medicinal plants are used for 11 categories of diseases, among which diseases of blood-forming organs (ICF = 0.96) and gastrointestinal diseases (ICF = 0.95) exhibited the highest ICF values. Based on the CI values, the most important plants in this study area are Berberis xanthophloea, B. kongboensis, Sinopodophyllum hexandrum, Vicatia thibetica, and Hippophae rhamnoides subsp. gyantsensis. Moreover, a comparison of the wild plants used by Lhoba ethnic groups in three counties in China showed significant differences among these regions. CONCLUSIONS: Our study demonstrates that the wild plants utilized by the Lhoba people in Douyu Village are highly diverse, at 90 plant and one fungal species, which reflects not only the number of species but also their diversified functions. The extreme climatic, geographical, and ecological conditions of Douyu within the high mountains and valleys of the Eastern Himalayas potentially affect the Lhoba people's culture, including plant utilization practices, and contribute to the rich diversity of the wild plants used by the local people.


Assuntos
Etnicidade , Etnobotânica , Plantas Medicinais , China , Humanos , Conhecimento , Fitoterapia , Tibet
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