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1.
World J Clin Cases ; 12(4): 700-720, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38322675

RESUMO

BACKGROUND: Breast cancer (BC), a leading malignant disease, affects women all over the world. Cancer associated fibroblasts (CAFs) stimulate epithelial-mesenchymal transition, and induce chemoresistance and immunosuppression. AIM: To establish a CAFs-associated prognostic signature to improve BC patient outcome estimation. METHODS: We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas (TCGA) databases, and 3661 BC samples from the The Gene Expression Omnibus. CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm. CAF-associated gene identification was done by weighted gene co-expression network analysis. A CAF risk signature was established via univariate, least absolute shrinkage and selection operator regression, and multivariate Cox regression analyses. The receiver operating characteristic (ROC) and Kaplan-Meier curves were employed to evaluate the predictability of the model. Subsequently, a nomogram was developed with the risk score and patient clinical signature. Using Spearman's correlations analysis, the relationship between CAF risk score and gene set enrichment scores were examined. Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Employing an 8-gene (IL18, MYD88, GLIPR1, TNN, BHLHE41, DNAJB5, FKBP14, and XG) signature, we attempted to estimate BC patient prognosis. Based on our analysis, high-risk patients exhibited worse outcomes than low-risk patients. Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis. ROC analysis exhibited satisfactory nomogram predictability. The area under the curve showed 0.805 at 3 years, and 0.801 at 5 years in the TCGA cohort. We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes. CAF risk score was significantly correlated with most hallmark gene sets. Finally, the prognostic signature were further validated by qRT-PCR. CONCLUSION: We introduced a newly-discovered CAFs-associated gene signature, which can be employed to estimate BC patient outcomes conveniently and accurately.

2.
Front Genet ; 14: 1271710, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028594

RESUMO

Background: Breast cancer, the most prevalent malignancy in women worldwide, presents diverse onset patterns and genetic backgrounds. This study aims to examine the genetic landscape and clinical implications of rare mutations in Chinese breast cancer patients. Methods: Clinical data from 253 patients, including sporadic and familial cases, were analyzed. Comprehensive genomic profiling was performed, categorizing identified rare variants according to the American College of Medical Genetics (ACMG) guidelines. In silico protein modeling was used to analyze potentially pathogenic variants' impact on protein structure and function. Results: We detected 421 rare variants across patients. The most frequently mutated genes were ALK (22.2%), BARD1 (15.6%), and BRCA2 (15.0%). ACMG classification identified 7% of patients harboring Pathogenic/Likely Pathogenic (P/LP) variants, with one case displaying a pathogenic BRCA1 mutation linked to triple-negative breast cancer (TNBC). Also identified were two pathogenic MUTYH variants, previously associated with colon cancer but increasingly implicated in breast cancer. Variants of uncertain significance (VUS) were identified in 112 patients, with PTEN c.C804A showing the highest frequency. The role of these variants in sporadic breast cancer oncogenesis was suggested. In-depth exploration of previously unreported variants led to the identification of three potential pathogenic variants: ATM c.C8573T, MSH3 c.A2723T, and CDKN1C c.C221T. Their predicted impact on protein structure and stability suggests a functional role in cancer development. Conclusion: This study reveals a comprehensive overview of the genetic variants landscape in Chinese breast cancer patients, highlighting the prevalence and potential implications of rare variants. We emphasize the value of comprehensive genomic profiling in breast cancer management and the necessity of continuous research into understanding the functional impacts of these variants.

3.
J Chin Med Assoc ; 85(11): 1051-1060, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36278918

RESUMO

BACKGROUND: The study aimed at exploring the expression of period circadian regulator 3 (PER3), a major member of the circadian clock gene family, and its biological function in breast cancer. METHODS: PER3-silencing and PER3-overexpression cell lines were established by transfecting with pGenesil1-PER3 and Lenti-blast-PER3 vector, respectively. RESULTS: The results showed that the expression of PER3 was downregulated in breast cancer tissues and cell lines ( p < 0.001), and its low expression was significantly correlated with advanced tumor stage ( p = 0.031) and advanced T stage ( p = 0.018). Cell functional experiments indicated that the silencing of PER3 elevated the ability of breast cancer cells to proliferate, invade, and metastasize in vitro ( p < 0.05), whereas overexpression of PER3 had an inhibitory effect on these malignant phenotype of breast cancer cells ( p < 0.05). Moreover, the activation of MEK/ERK signaling pathway was evidently inhibited by silencing of PER3, as evidenced by decreased expression levels of p-MEK and p-ERK1/2 proteins in breast cancer cells ( p < 0.05). PER3-silencing and PER3-overexpression cells were treated with PD98059 (an inhibitor of MEK/ERK signaling) and TPA (an activator of MEK/ERK signaling), respectively. It was observed that PER3 silencing-mediated malignant phenotype in breast cancer cells was markedly suppressed by PD98059 treatment. Instead, TPA exposure reversed the inhibitory effects of PER3 overexpression on DNA synthesis, proliferation, migration, and invasion of breast cancer cells. CONCLUSION: These findings suggested that PER3 function as a tumor suppressor in the development and progression of breast cancer and its anticancer roles might be dependent on the MEK/ERK signaling pathway.


Assuntos
Neoplasias da Mama , Carcinogênese , Sistema de Sinalização das MAP Quinases , Proteínas Circadianas Period , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Circadianas Period/genética , Transdução de Sinais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino
4.
Aging (Albany NY) ; 13(19): 22947-22962, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610582

RESUMO

Diffuse large B-cell lymphoma (DLBCL) presents a great clinical challenge and has a poor prognosis, with immune-related genes playing a crucial role. We aimed to develop an immune-related prognostic signature for improving prognosis prediction in DLBCL. Samples from the GSE31312 dataset were randomly allocated to discovery and internal validation cohorts. Univariate Cox, random forest, LASSO regression and multivariate Cox analyses were utilized to develop a prognostic signature, which was verified in the internal validation cohort, entire validation cohort and external validation cohort (GSE10846). The tumor microenvironment was investigated using the CIBERSORT and ESTIMATE tools. Gene set enrichment analysis (GSEA) was further applied to analyze the entire GSE31312 cohort. We identified four immune-related genes (CD48, IL1RL, PSDM3, RXFP3) significantly associated with overall survival. Based on discovery and validation cohort analyses, this four-gene signature could classify patients into high- and low-risk groups, with significantly different prognoses. Activated memory CD4 T cells and activated dendritic cells were significantly decreased in the high-risk group, and these patients had lower immune scores. GSEA revealed enrichment of signaling pathways, such as T cell receptor, antigen receptor-mediated, antigen processing and presentation of peptide antigen via MHC class I, in the low-risk group. In conclusion, a robust signature based on four immune-related genes was successfully constructed for predicting prognosis in DLBCL patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos/fisiologia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Prognóstico , Reprodutibilidade dos Testes
5.
J Surg Res ; 257: 501-510, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916503

RESUMO

BACKGROUND: Breast cancer is a familiar malignant tumor, which is a great threat to women's life. Long noncoding RNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) has been reported to be associated with numerous cancers. This study aimed to explore the role of OIP5-AS1 and the mechanism of its action in the progression of breast cancer. METHODS: The expression of OIP5-AS1 and miR-216a-5p was detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, or invasion was assessed by 4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, flow cytometry, or transwell assay, respectively. The binding sites were predicted by bioinformatics tool starBase2.0 (http://starbase.sysu.edu.cn/starbase2/index.php). The interaction between miR-216a-5p and OIP5-AS1 or glyoxalase 1 (GLO1) was confirmed by dual-luciferase reporter assay. The expression of GLO1 was quantified by Western blot. Nude mouse tumorigenicity assays were conducted to verify the role of OIP5-AS1 in vivo. RESULTS: OIP5-AS1 and GLO1 were highly expressed in both clinical tumor tissues and cell lines, whereas miR-216a-5p was downregulated. Knockdown of OIP5-AS1 suppressed proliferation, migration, and invasion but promoted apoptosis of breast cancer cells. MiR-216a-5p was a target of OIP5-AS1 and interacted with GLO1. MiR-216a-5p inhibition or GLO1 overexpression reversed the effects of OIP5-AS1 knockdown on the development of breast cancer cells. OIP5-AS1 knockdown depleted tumor growth in vivo. CONCLUSIONS: OIP5-AS1 knockdown suppressed the progression of breast cancer by inducing GLO1 expression via competitively binding to miR-216a-5p, suggesting that OIP5-AS1 was a hopeful biomarker for the therapy of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Lactoilglutationa Liase/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Camundongos Nus
6.
J Biomed Nanotechnol ; 16(1): 65-75, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996286

RESUMO

Objective: To investigate the innovative application of gold nanorods combined with a laser in posttraumatic osteoarthritis (PTOA) modeling and to discuss the possible mechanisms. Methods: Electron microscopy was used to characterize the gold nanorods. Cell counting kit-8 assay and enzyme-linked immunosorbent assay were used to evaluate cell proliferation and cytotoxicity. An infrared spectroscopy (IR) thermal camera was used to monitor the temperature changes of gold nanorods with or without the laser treatment. Furthermore, western blotting was used to evaluate the expression of related proteins in response to the indicated treatments. Finally, microcomputed tomography (micro-CT) was used to determine the structural changes in knee joints. Changes in the cartilage and various other tissues were assessed by histological examination. Results: The characteristics and biosafety of the gold nanorods were confirmed. Our study showed that gold nanorods combined with the laser inhibited cell viability, but the gold nanorods or laser alone did not affect cell viability. Moreover, the effect on cell viability was time dependent. Similarly, only gold nanorods with the laser caused the apoptosis of cartilage cells and the upregulation of IL-1ß, MMP-13 and Comp. We injected gold nanorods and used laser irradiation to develop an osteoarthritis (OA) model. The temperature of the knees in the OA model increased to 60 °C and then remained at approximately 60 °C. As the time increased, gold nanorods combined with the laser caused more injuries and degeneration in the knee joints. Conclusion: OA models that were established using gold nanorods and a laser were precise, controllable, observable and stable and could be an excellent premise for investigating the exact mechanisms underlying OA and exploring new treatment strategies.


Assuntos
Nanotubos , Osteoartrite , Cartilagem , Ouro , Humanos , Microtomografia por Raio-X
7.
Toxicol Appl Pharmacol ; 362: 20-27, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30292833

RESUMO

Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We orally exposed AlCl3 (10 mg/L) to Sprague-Dawley rats in drinking water for 12 weeks while NMN (20 mg/kg) were intraperitoneally injected in last 4 weeks. We found that Al could induce bone damages, bone loss and oxidative stress. In addition, we showed that Al triggered inflammatory responses, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. However, NMN treatment significantly alleviated Al-induced bone injuries by decreasing bone loss, suppressing oxidative stress as well as inhibiting Thioredoxin-interacting protein (TXNIP)-NLRP3 inflammasome pathway and pro-inflammatory cytokine production in vivo and in vitro. Meanwhile, treatment with TXNIP siRNA performed the same protective effects as NMN in Al-treated MC3T3-E1 cells. Collectively, our results suggest that NMN may reduce Al-induced bone loss partly by suppression of the TXNIP-NLRP3 inflammasome pathway.


Assuntos
Cloreto de Alumínio/toxicidade , Reabsorção Óssea/tratamento farmacológico , Proteínas de Transporte/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Mononucleotídeo de Nicotinamida/uso terapêutico , Animais , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/diagnóstico por imagem , Reabsorção Óssea/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Ratos Sprague-Dawley , Microtomografia por Raio-X
8.
Int Orthop ; 43(7): 1679-1683, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30022218

RESUMO

PURPOSE: To promote the understanding of pelvic fracture mechanism and make more accurate evaluation of maximal deformity at the moment of fracture, kinematic response of pelvis to lateral impact and the difference between peak and final displacement were investigated. METHODS: A total of three human cadaver pelves were seated uprightly on a sled test table, explored to horizontal lateral impact by a 22.1-kg impactor at a speed of 5.2, 4.0, and 4.8 m/s. Kinematic data of pelvic osseous interesting points (POIP) were measured by the motion capture system. Trajectories of POIP, duration of impact, and deflection of pelvis were calculated as well as rotational movement of pelvis was evaluated. After impact, autopsy and CT scan were made to validate the motion capture data. RESULTS: The peak deflection of pelvis under lateral impact was 31.9, 30.1, and 18.5%, while final deflection was 19.6, 13.8, and 13.8%. The final deflection was only 61.5, 45.9, and 74.46% of the peak deflection. CONCLUSIONS: In clinical practice, pelvic fracture displacement tends to be underestimated. The peak compression can be 1.3-2.2 times of final compression appearing on images in hospital. Clinicians shall give adequate estimation of displacement and related injuries.


Assuntos
Fraturas Ósseas/fisiopatologia , Fraturas por Compressão/fisiopatologia , Ossos Pélvicos/fisiopatologia , Fenômenos Biomecânicos , Cadáver , Fraturas Ósseas/diagnóstico por imagem , Fraturas por Compressão/diagnóstico por imagem , Humanos , Masculino , Modelos Anatômicos , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Tomografia Computadorizada por Raios X
9.
Zhongguo Gu Shang ; 31(9): 794-798, 2018 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-30332869

RESUMO

OBJECTIVE: To explore the effect of postoperative initial neck stem angle on the treatment of proximal humeral fractures with locking plate. METHODS: From June 2014 to Septembetr 2016, 62 patients with proximal humeral fractures underwent internal fixation with locking plates were retrospectively analyzed, including 29 males and 33 females with an average age of(55.95±9.48) years old ranging from 34 to 74 years old. According to the difference of the initial neck stem angle, the patients were divided into three groups, 15 patients in the varus group had less than 127° postoperative initial neck-shaft angle, 36 patients in the normal group had 127° to 145° postoperative initial neck-shaft angle, 11 patients in the valgus group had more than 145° postoperative initial neck-shaft angle. The operating time, fracture healing time, complications, the visual analogue scale(VAS) and shoulder functional Neer scores among three groups were compared for analysis. RESULTS: All 62 patients were followed up for 17.2 months(ranged 12 to 38 months). Operative time, fracture healing time and VAS were(2.37±0.59) hours, (3.99±0.48) months and(3.67±2.02) points in the varus group;(2.60±0.49) hours, (3.78±0.49) months and(3.22±2.06) points in the normal group;(2.75±0.39) hours, (3.82±0.42) months and (4.09±1.58) points in the valgus group. There was no statistical difference in operating time, fracture healing time and VAS among these groups(P>0.05). The Neer score(87.14±6.48) in the normal group and(84.31±9.05) in the valgus group was significantly better than(75.93±9.77) in the varus group (P<0.05). Among them, 4 cases occurred complications in the varus group;2 cases in the normal group;while no complication occurred in the valgus group. CONCLUSIONS: The internal fixation with locking plates of the proximal humerus fractures with postoperative initial neck-shaft angle more than 127° can reduce complications, improve shoulder function and allow for better postoperative outcome.


Assuntos
Fraturas do Ombro , Adulto , Idoso , Placas Ósseas , Feminino , Fixação Interna de Fraturas , Humanos , Úmero , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
10.
J Biomed Nanotechnol ; 14(1): 127-138, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29463370

RESUMO

Drug delivery system studies aim to improve nanoparticle (NP) formulation to enable efficient delivery of NPs to tumors. However, NPs must be transported by blood or through direct injection. How NPs leave the circulatory system and how NPs diffuse into a tumor remain unclear, and this uncertainty is a limitation of drug delivery systems. The intimate connection between these questions and metabolism may be related to their biosafety in vivo. Thus, in this study, classical carrier SiO2 NPs were used as typical transport NPs, and fluorescein isothiocyanate (FITC) was used as the representative drug and tracer. As exosome and tunneling nanotubes (TNTs) are the most relevant mechanism for NP transportation and considering the local situation in a tumor, we focused on identifying this phenomenon and investigating TNTs. In conclusion, we effectively demonstrated that NPs can be transferred from cell to cell. Nanotubes may play an important role in this process.


Assuntos
Sistemas de Liberação de Medicamentos , Fluoresceína-5-Isotiocianato , Nanopartículas , Dióxido de Silício , Fluoresceína , Neoplasias/tratamento farmacológico
11.
Int J Nanomedicine ; 13: 103-116, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29317819

RESUMO

The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a transwell migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.


Assuntos
Antineoplásicos/farmacologia , Cobre/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Nanopartículas/química , Animais , Antineoplásicos/administração & dosagem , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Quinase 1 de Adesão Focal/metabolismo , Células HeLa , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos Nus , Polietilenoglicóis/química , Transdução de Sinais/efeitos dos fármacos , Dióxido de Silício/química , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Chin J Traumatol ; 21(6): 356-359, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30598337

RESUMO

PURPOSE: Exposure of the articular surface is the key to the successful treatment of intra-articular fractures of distal humerus. Anterior, posterior olecranon osteotomy as well as medial and lateral approaches are the four main approaches to the elbow. The aim of this study was to compare the exposure of distal articular surfaces of these surgical approaches. METHODS: Twelve cadavers were used in this study. Each approach was performed on six elbows according to previously published procedures. After completion of each approach, the exposed articular surfaces were marked by inserting 0.5 mm K-wires along the margins. The elbow was then disarticulated and the exposed articular surfaces were painted. The distal humeral articular surfaces were then closely wrapped using a piece of fibre-glass screen net with meshes. The exposed articular surfaces and the total articular surfaces were calculated by counting the number of meshes, respectively. RESULTS: The average percentages of the exposed articular surfaces for the anterior, posterior olecranon osteotomy, medial and lateral approaches were 45.7% ± 2.0%, 53.9% ± 7.1%, 20.6% ± 4.9% and 28.5% ± 6.3%, respectively. CONCLUSION: The anterior and posterior approaches provide greater exposures of distal humeral articular surface than the medial and lateral ones in the treatment of distal humeral fractures.


Assuntos
Articulação do Cotovelo/cirurgia , Cotovelo/cirurgia , Fraturas do Úmero/cirurgia , Úmero/cirurgia , Fraturas Intra-Articulares/cirurgia , Osteotomia/métodos , Adulto , Idoso , Cadáver , Humanos , Masculino , Pessoa de Meia-Idade
13.
Oncotarget ; 8(40): 68809-68824, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28978158

RESUMO

Single nucleotide polymorphisms (SNPs) in three microRNAs (miRNAs), rs2910164 in miR-146a, rs11614913 in miR-196a2, and rs3746444 in miR-499, have been associated with breast cancer (BC) susceptibility, but the evidence is conflicting. To obtain a more robust assessment of the association between these miRNA variants and BC risk, we carried out a meta-analysis through systematic literature retrieval from the PubMed and Embase databases. A total of 9 case-control studies on rs2910164, 12 on rs11614913, and 7 on rs3746444 were included. Pooled odds ratios and 95% confidence intervals were used to evaluate associations with BC risk. Overall analysis showed that rs2910164 was not associated with BC susceptibility in any genetic model, whereas rs11614913 was associated with a decreased risk in both the allelic contrast and recessive models, and rs3746444 imparted an increased risk in all genetic models. Stratified analyses showed that rs11614913 may decrease the risk of BC in the heterozygote model in Asians, and in all genetic models, except the heterozygote model, when the sample size is ≥ 500. Subgroup analysis indicated that rs3746444 was associated with increased risk of BC in Asians, but not Caucasians, at all sample sizes. This meta-analysis suggests that rs11614913 in miR-196a2 may decrease the risk of BC, while rs3746444 in miR-499 may increase it, especially in Asians when the sample size is large. We propose that rs11614913(C > T) and rs3746444 (A > G) may be useful biomarkers predictive of BC risk.

14.
Cancer Biol Med ; 13(1): 142-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27144069

RESUMO

OBJECTIVE: Survival and treatment of patients with microinvasive breast cancer (MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy. METHODS: In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer (AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups. We compared the 5-year disease-free survival (DFS) and overall survival (OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months (13-104 months). RESULTS: The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the non-chemotherapy group were 89.7% and 100%. RESULTS indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS (P=0.223) or OS (P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2% vs. 86.5% between low Ki-67 (≤20%) and high Ki-67 (>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval (CI), 1.969-139.724; P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149 (95% CI, 3.702-99.057; P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients (P=0.014), but not those who overexpress Ki-67 (P=0.105). CONCLUSIONS: Patients with MIBC who overexpress Ki-67 and with negative hormonal receptors have relatively substantial risk of relapse within the first five years after surgery. However, adjuvant chemotherapy can only improve the outcomes of ER(-)/PR(-) patients, but not those who overexpress Ki-67. Further studies with prolonged follow-up of large cohorts are recommended to assess the prognostic significance and treatment of this lesion.

15.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 28(10): 1217-20, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25591295

RESUMO

OBJECTIVE: To investigate the biomechanical properties of artificial ligament in the treatment of injuries to distal tibiofibular syndesmosis so as to provide a scientific basis for clinical application. METHODS: Sixteen fresh ankle specimens were harvested from 8 normal fresh-frozen cadavers. The initial tests were performed on 16 intact specimens (group A) and then the distal tibiofibular syndesmosis injury models were made (group B); the distal tibiofibular syndesmosis was fixed with artificial ligament in 8 specimens (group C) and with cannulated lag screw in the other 8 specimens (group D). The pros and cons of different fixation methods were analyzed by displacement, stress shielding effect, the strength and stiffness of ankle joints, the contact area of tibiotalar articular surface and the contact stress. RESULTS: Under the physiological loading or combined with external rotation moment, the displacement of group C was significantly lower than that of groups B and D (P < 0.05), but no significant difference was found between groups A and C (P > 0.05); and there were significant differences among groups A, B, and D (P < 0.05). The rates of stress shielding in the tibia and fibula of group C were significantly lower than those of group D (t = -71.288, P = 0.000; t = -97.283, P = 0.000). The stress strength in tibia of group C was significantly higher than that of groups A and D (P < 0.05), but no significant difference was found between groups A and D (P > 0.05). Group C had the highest stress strength in fibula, followed by group A, group D had the lowest; differences were significant among 3 groups (P < 0.05). There was no significant difference in shear strength among groups A, C, and D (P > 0.05). The axial stiffness in tibia of group D was significantly lower than that of groups A and C (P < 0.05), but no significant difference was found between groups A and C (P > 0.05). The axial stiffness in fibula of group C was significantly higher than that of groups A and D (P < 0.05), but no significant difference was found between groups A and D (P > 0.05). Group C had the highest shear stiffness in tibia and fibula, followed by group D,group A had the lowest; differences were significant among 3 groups (P < 0.05). In groups A, C, and D, the contact area of tibiotalar articular surface gradually reduced, and the contact stress gradually increased, and differences were significant among 3 groups (P < 0.05). CONCLUSION: Fixation of distal tibiofibular syndesmosis injury with artificial ligament can better meet the physiological functions of the distal tibiofibular syndesmosis and has lower stress shielding, better stress distribution. Hopefully, it can reduce the complications of the distal tibiofibular syndesmosis injuries and become a better treatment choice.


Assuntos
Traumatismos do Tornozelo/fisiopatologia , Articulação do Tornozelo , Fíbula/fisiopatologia , Ligamentos Articulares/fisiopatologia , Tíbia/fisiopatologia , Traumatismos do Tornozelo/cirurgia , Fenômenos Biomecânicos , Parafusos Ósseos , Cadáver , Feminino , Humanos , Luxações Articulares/fisiopatologia , Instabilidade Articular/fisiopatologia , Masculino , Modelos Biológicos , Amplitude de Movimento Articular/fisiologia , Rotação , Suporte de Carga/fisiologia
16.
Artigo em Chinês | MEDLINE | ID: mdl-17036980

RESUMO

OBJECTIVE: To investigate the effect of magnesium phosphate cement (MPC) to fix fractures. METHODS: In vitro: fifty-four pairs of fresh pig femoral heads were made 1 cm2 fracture and divided into 6 groups (n=9 pairs ). MPC was used to agglutinate fracture of femoral heads at 100% humidity and at 25 degrees C, 37 degrees C respectively. At 30 minutes, 2 and 24 hours after agglutination, the biomechanical strength was measured. In vivo: the tibia plateau fracture models on both sides of 24 rabbits were made, one side was fixed with "L" shaped plate, and the other side was fixed with MPC. Then the effect of treatment was investigated by macrography, micrography, radiography and the In vitro: the adhesive ability of changes of serum electrolyte levels at 3 days, 3, 6 and 9 weeks after operation. RESULTS: MPC was strong. At 24 hours after MPC agglutination, the average tensile strength was 117.16 +/- 23.29 N/cm2. In vivo: after 6 weeks of fixation, the X-ray results showed that all rabbits' tibia plateau fractures were healed without displacement, and MPC was absorbed gradually. The changes of serum electrolyte levels were very minimal. The macrography observation showed that reduction of fracture were good at 3 days after operation, partial MPC remained in fracture end at 3 weeks, fracture line disappeared at 6 weeks and good remodeling was achieved at 9 weeks after operation in the experimental group. The micrography observation showed that the interface between bone and MPC was distinct at 3 days, MPC was degraded gradually and trabeculae began to grow into MPC at 3 weeks, and almost all MPC was degraded at 6 and 9 weeks of operation. CONCLUSION: MPC is a promising biomaterial, and might potentially be used for fracture treatment.


Assuntos
Cimentos Ósseos/uso terapêutico , Fraturas do Colo Femoral/cirurgia , Compostos de Magnésio/uso terapêutico , Fosfatos/uso terapêutico , Fraturas da Tíbia/cirurgia , Animais , Placas Ósseas , Modelos Animais de Doenças , Feminino , Fixação Interna de Fraturas/métodos , Masculino , Coelhos , Suínos
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