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BACKGROUND: One of the ongoing debates about carotid endarterectomy (CEA) is the closure technique of arterial wall in the operation. Current guidelines recommend routine patch closure (PAC); this recommendation is based on the evidence reported 10-20 years ago. Therefore, the exact role of PAC and primary closure (PRC) remains uncertain. The objectives of this study were to compare the perioperative and long-term outcomes of patients who underwent CEA with different closure techniques. METHODS: From January 2013 and December 2018, one senior vascular surgeon performed CEA for 126 patients in the First Affiliated Hospital, Sun Yat-sen University. The closure technique (PAC or PRC) was determined on the characteristics (diameter and level) of carotid arteries. Patient demographics and clinical data were retrospectively collected by two research fellows by reviewing the hospital medical records and relevant radiologic studies, as were carotid duplex reports, indications, intraoperative data, closure technique, and perioperative complications. Data of long-term outcomes were gathered by reviewing outpatient clinic visits and associated supplementary examinations. RESULTS: PRC was performed in 78 operations (61.9%), and PAC was performed in 48 operations (38.1%). There were no statistical differences in demographic and clinical data between the two groups. Carotid clamp time (P < 0.001) and operating time (P < 0.001) were significantly longer when performing PAC (P < 0.001), and intraoperative blood loss was significantly more when performing PAC than that of PRC (P < 0.001). The postoperative outcome and the follow-up results showed that there was no significant difference in the short-term and middle-term overall survival rate and restenosis-free survival rate between the two groups. CONCLUSIONS: There are no differences in postoperative and middle-term outcomes between PAC and selective PRC, whereas PRC technique can save operation time and shorten the intraoperative carotid clamp time. PRC can be safely applied in patients with a greater than 5 mm internal carotid artery (ICA).
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Angioplastia/instrumentação , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Idoso , Angioplastia/efeitos adversos , Angioplastia/mortalidade , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , China , Constrição , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Sustaining proliferation is the most fundamental step for breast cancer tumor genesis. Accelerated proliferation is usually linked to the uncontrolled cell cycle. However, the internal and external factors linked to the activation of breast cancer cell cycle are still to be investigated. METHODS: quantitative PCR (qPCR) and Western blotting assay were used to detect the expression of potassium channel tetramerization domain containing 12 (KCTD12) in breast cancer. MTT and colony formation assays were performed to evaluate the effect of KCTD12 on cell proliferation of breast cancer. Anchorage-independent growth assay was used to examine the in vitro tumorigenesis of breast cancer cells. Flow cytometry assay, qPCR, and Western blotting were used to investigate the detailed mechanisms of KCTD12 on breast cancer progression. RESULTS: Herein, the result showed that the level of KCTD12 is significantly decreased in breast cancer tissues and cells, and lower level of KCTD12 predicts poorer survival for patients with breast cancer. Further cell function tests illustrated that downregulation of KCTD12 significantly promotes cell proliferation and in vitro tumor genesis. Besides, molecular biologic experiments showed that downregulation of KCTD12 can enhance the G1/S transition through activating the AKT/FOXO1 signaling. CONCLUSION: Our study inferred that downregulation of KCTD12 can be a novel factor for poor prognosis in breast cancer.
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Neoplasias da Mama , Ciclo Celular/genética , Proteína Forkhead Box O1/genética , Proteínas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Proteína Forkhead Box O1/metabolismo , Humanos , Prognóstico , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genéticaRESUMO
BACKGROUND: This study aims to present the performance data on stent-graft and multilayer bare stents (MBS) joint technique in the treatment of high-risk thoracoabdominal aortic aneurysm (TAAA). METHODS: From May 2012 to December 2015, 8 selective TAAA cases (ages 46-75 years) ineligible for surgical repair underwent the stent-graft and MBS joint procedure, and were closely followed up for a median of 32 months (range 14-58). Using computed tomography images, the aneurysm size, luminal blood flow diameter, and the covered visceral branches were analyzed. RESULTS: Technical success was achieved in all patients (100%, 8/8). Twenty-four visceral branches were covered by MBS in total. There was no complication or death during hospital stay. During follow-up period, no death or complication occurred. Aneurysm shrinkage (maximum diameter decrease ≥5 mm) was observed in 7 patients. No aneurysm expansion was observed. Total aneurysm sac thrombosis was observed in all patients. The majority of covered side branches (23/24) were successfully preserved. No visceral ischemia or bleeding complications was observed during follow-up. CONCLUSIONS: Total endovascular repair of TAAA using stent-graft and MBS joint technique may be a safe and effective alternative in high surgical risk patients. More approving clinical evidences about the safety and efficacy of this procedure are anticipated.
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Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Idoso , Aneurisma da Aorta Torácica/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Atherosclerotic diseases may include femoropopliteal artery stenosis or occlusion. Percutaneous transluminal angioplasty (PTA) is an effective and minimally invasive treatment strategy for atherosclerotic femoropopliteal artery stenosis/occlusion disease. Balloon angioplasty is a widely used technique in the management of occlusive disease in almost all arterial segments.We enrolled 111 diabetics with long femoropopliteal lesions, among which 54 received PTA with paclitaxel-coated balloon (the Paclitaxel group), and 57 with standard balloon catheters (the Control group).The primary outcome was set as angiographic late lumen loss (LLL) within 6 months; the secondary angiographic outcome was binary restenosis. Clinical outcomes included Rutherford clarification, ankle-brachial index (ABI) and rate of clinically driven target lesion revascularization (TLR). Two groups had similar basal clinical features, angiographic and procedural characteristics. Compared to controls, the Paclitaxel group had a significantly lower 6-month LLL rate, 12-month binary restenosis rate, 12-month TLR, lower Rutherford grades at 3 and 6 months, and higher ABI at 3 months. For all factors which might influence outcomes, fasting blood glucose was negatively correlated with ABI; the blood urea nitrogen (BUN) was positively related with the Rutherford clarification grades. In addition, the coronary heart disease (CHD) and smoking histories were positively correlated with residual stenosis after treatment.Collectively, the paclitaxel-coated balloon angioplasty can yield more favorable angiographic and clinical outcomes than standard uncoated balloon angioplasty, even in the more challenging lesions (the long and occlusive femoropopliteal lesions) in diabetics, when it had a similar safety profile to the traditional balloon. Blood glucose, BUN, CHD, and smoking imply poor curative effects.
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Angioplastia com Balão/métodos , Angioplastia/métodos , Materiais Revestidos Biocompatíveis/uso terapêutico , Diabetes Mellitus/epidemiologia , Artéria Femoral/patologia , Artéria Poplítea/patologia , Idoso , Angiografia/métodos , Angioplastia/efeitos adversos , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/estatística & dados numéricos , Antineoplásicos Fitogênicos/uso terapêutico , Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/terapia , Aterosclerose/complicações , Materiais Revestidos Biocompatíveis/efeitos adversos , Materiais Revestidos Biocompatíveis/normas , Complicações do Diabetes , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Doença Arterial Periférica/patologia , Doença Arterial Periférica/terapia , Artéria Poplítea/diagnóstico por imagem , Resultado do TratamentoRESUMO
AIM: In-Stent Restenosis (ISR) is the major reason for recurrent ischemia and amputation after endovascular treatment of Peripheral Artery Disease (PAD). Our previous study demonstrated that miR-140-3p is significantly down-regulated in PAD arteries. However, expression and function of miR-140-3p in ISR of human PAD are currently unclear.The aim of this study is to determine the miR-140-3p expression and its regulative role in ISR of PAD. METHODS: The RNA level was determined by quantitative real-time polymerase chain Reaction (qRT-PCR) and in situ hybridization. Primary cultured ASMCs were isolated from human femoral arterial of the healthy donors or ISR patients. Cell proliferation was determined by Edu incorporation and CCK-8 assay. Apoptosis was determined by Annexin-â ¤/PI Double-Staining assay and TUNEL assay. A rat carotid artery balloon angioplasty model was used to investigate the effect of miR-140-3p on restenosis. RESULTS: MiR-140-3p was significantly down-regulated in PAD and ISR arteries than normal arteries. Primary cultured ISR ASMCs exhibited elevated proliferation and down-regulated miR-140-3p than normal ASMCs. Transfection of miR-140-3p mimic attenuated PDGF-BB-induced proliferation in cultured ASMCs and induced apoptosis. Luciferase reporter assay indicated that miR-140-3p transfection significantly down-regulated C-Myb and BCL-2 in ISR ASMCs by targeting to their 3'-UTRs. MiR-140-3p transfection induced anti-proliferation and apoptosis in ASMCs, which were ameliorated by over-expression of C-Myb or BCL-2. Moreover, the animal study showed that miR-140-3p can reduce restenosis following angioplasty via targeting C-Myb and BCL-2. CONCLUSIONS: The result suggests that miR-140-3p regulates ASMC function via targeting C-Myb and BCL-2 in the process of ISR in PAD. The novel findings may offer a hopeful therapeutic target for human PAD.
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Lesões das Artérias Carótidas/veterinária , Reestenose Coronária/etiologia , MicroRNAs/genética , Doença Arterial Periférica/cirurgia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myb/metabolismo , Stents/efeitos adversos , Animais , Apoptose , Biomarcadores/análise , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Proliferação de Células , Células Cultivadas , Reestenose Coronária/metabolismo , Reestenose Coronária/patologia , Modelos Animais de Doenças , Seguimentos , Humanos , Masculino , Doença Arterial Periférica/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myb/genética , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND/AIMS: ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2). To date, ALT1 biological roles in human vascular endothelial cells have not been reported. METHODS: ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3' rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. RESULTS: ALT1 was expressed in human umbilical vein endothelial cells (HUVECs). The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme â ¡(ACE2) was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL) might be involved. CONCLUSION: The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.
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Peptidil Dipeptidase A/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Enzima de Conversão de Angiotensina 2 , Apoptose , Proteínas de Transporte/metabolismo , Hipóxia Celular , Proliferação de Células , Proteínas Culina/antagonistas & inibidores , Proteínas Culina/genética , Proteínas Culina/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas do Citoesqueleto , Regulação para Baixo , Pontos de Checagem da Fase G1 do Ciclo Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imunoprecipitação , MicroRNAs/metabolismo , Chaperonas Moleculares , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/genética , Interferência de RNA , RNA Longo não Codificante , RNA Interferente Pequeno/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Transferases , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , UbiquitinaçãoRESUMO
BACKGROUND: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post-angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation. METHODS: Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. RESULTS: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. CONCLUSIONS: Our results indicate that miR-22-3p is a key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO.
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Arteriosclerose Obliterante/patologia , Proteína HMGB1/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Arteriosclerose Obliterante/metabolismo , Sequência de Bases , Becaplermina , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/veterinária , Movimento Celular , Proliferação de Células , Células Cultivadas , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/genética , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Proteínas Proto-Oncogênicas c-sis/farmacologia , Ratos , Ratos Sprague-Dawley , Alinhamento de SequênciaRESUMO
The transcriptional factor Osterix is specifically expressed in bone tissues to regulate the differentiation and maturation of osteoblasts. Recent studies have also identified the expression of Osterix in a number of cancer tissues, such as kidney and lung cancers. However, the association of Osterix with the metastasis of breast cancers has never been reported. The present study, for the first time, provides evidence supporting the involvement of Osterix in breast cancer metastasis. Western blotting was employed to investigate the expression of Osterix in a number of human breast cancer cell lines with different metastatic features. Gain-of-function and loss-of-function experiments were performed in MCF7 cells (low level of metastasis) and MDA-MB-361 cells (high level of metastasis). The expression of several metastasis-associated genes was analyzed by western blotting and quantitative polymerase chain reaction. A firefly luciferase-based reporter gene assay was conducted in order to study whether Osterix regulated the promoter activities of the MMP2 and MMP9 genes, which play critical roles in cancer metastasis. The results showed that Osterix was highly expressed in the MDA-MB-231 and MDA-MB-361 cells, but was not detectable in the MCF7 cells. The overexpression of Osterix in the MCF7 cells promoted the expression of VEGF, MMP9 and ß-catenin, while downregulating the expression of E-cadherin. In addition, suppression of Osterix expression in the MDA-MB-361 cells reversed the alteration of VEGF, MMP9, ß-catenin and E-cadherin expression. A reporter gene assay suggested that Osterix activated MMP2 and MMP9 promoter activity. In conclusion, Osterix is involved in the metastasis of human breast cancer and may be a target for the efficient treatment of human breast cancers.
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AIMS: To explore the expression of miR-24-3p in human arteries with arteriosclerosis obliterans (ASO) as well as the role of miR-24-3p in the pathogenesis of ASO. METHODS: We used quantitative real-time PCR (qRT-PCR) and in situ hybridization to monitor miR-24-3p expression in human arteries. To investigate the effect of miR-24-3p on human arterial smooth muscle cells (HASMCs), we applied cell counting and EdU assays to monitor proliferation and transwell and wound healing assays to investigate migration and flow cytometry to investigate apoptosis. Furthermore, we applied 3'-untranslated region (3'-UTR) luciferase assays to investigate the role of miR-24-3p in targeting platelet-derived growth factor receptor B (PDGFRB) and c-Myc. RESULTS: MiR-24-3p was mainly located in the media of arteries and was downregulated in ASO arteries compared with normal arteries. Platelet-derived growth factor BB (PDGF-BB) treatment reduced the expression of miR-24-3p in primary cultured HASMCs. MiR-24-3p mimic oligos inhibited the proliferation and migration, and promotes apoptosis of HASMCs. Our 3'-UTR luciferase assays confirmed that PDGFRB and c-Myc were targets of miR-24-3p. CONCLUSION: The results suggest that miR-24-3p regulates the proliferation and migration of HASMCs by targeting PDGFRB and c-Myc. The PDGF/miR-24-3p/PDGFRB and PDGF/miR-24-3p/c-Myc pathways may play critical roles in the pathogenesis of ASO. These findings highlight the potential for new therapeutic targets for ASO.
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Apoptose , Arteriosclerose Obliterante/genética , Movimento Celular , Proliferação de Células , Regulação da Expressão Gênica , MicroRNAs/genética , Miócitos de Músculo Liso/patologia , Arteriosclerose Obliterante/patologia , Sequência de Bases , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genéticaRESUMO
Heme oxygenase-1 (HMOX-1) is a microsomal enzyme that exerts anti-apoptotic and cytoprotective effects. In the present study, HMOX-1 was demonstrated to be overexpressed and able to be induced by doxorubicin in breast cancer cell lines. Knockdown of HMOX-1 using short interfering (si)RNA enhanced the cytotoxicity of doxorubicin in MDA-MB-231 and BT549 cells. Knockdown of HMOX-1 downregulated B cell lymphoma (Bcl)-2 and Bcl-extra large expression, and significantly enhanced doxorubicin-induced apoptosis in MDA-MB-231 and BT549 cells. Additionally, knockdown of HMOX-1 upregulated light chain 3B expression and markedly increased the accumulation of autophagic vacuoles in MDA-MB-231 and BT549 cells treated with doxorubicin. These results indicated that HMOX-1 may be involved in conferring the chemoresistance of breast cancer cells, by preventing apoptosis and autophagy. Therefore, HMOX-1 may represent a potential therapeutic target for enhancing the cytotoxicity and efficacy of doxorubicin during the treatment of breast cancer.
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Normal high density lipoprotein (HDL) protects vascular function; however these protective effects of HDL may absent in valvular heart disease (VHD). Because vascular function plays an important role in maintaining the circulation post-cardiac surgery and some patients are difficult to stabilize, we hypothesized that a deleterious vascular effect of HDL may contribute to vascular dysfunction in VHD patients following surgery. HDL was isolated from age-match 28 healthy subjects and 84 patients with VHD and during cardiac surgery. HDL pro-inflammation index was measured and the effects of HDL on vasodilation, protein interaction, generation of nitric oxide (NO) and superoxide were determined. Patients with VHD received either simvastatin (20mg/d) or routine medications, and endothelial effects of HDL were characterized. HDL inflammation index significantly increased in VHD patients and post-cardiac surgery. HDL from VHD patients and post-cardiac surgery significantly impaired endothelium-dependent vasodilation, inhibited both Akt and endothelial nitric oxide synthase (eNOS) phosphorylation at S1177, eNOS associated with heat shock protein 90 (HSP90), NO production and increased eNOS phosphorylation at T495 and superoxide generation. Simvastatin therapy partially reduced HDL inflammation index, improved the capacity of HDL to stimulate eNOS and Akt phosphorylation at S1177, eNOS associated with HSP90, NO production, reduced eNOS phosphorylation at T495 and superoxide generation, and improved endothelium-dependent vasodilation. Our data demonstrated that HDL from VHD patients and cardiac surgery contributed to endothelial dysfunction through uncoupling of eNOS. This deleterious effect can be reversed by simvastatin, which improves the vasoprotective effects of HDL. Targeting HDL may be a therapeutic strategy for maintaining vascular function and improving the outcomes post-cardiac surgery.
Assuntos
Doenças das Valvas Cardíacas/metabolismo , Valvas Cardíacas/metabolismo , Lipoproteínas HDL/metabolismo , Adulto , Idoso , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Estudos de Casos e Controles , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Feminino , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Valvas Cardíacas/efeitos dos fármacos , Valvas Cardíacas/patologia , Humanos , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sinvastatina/uso terapêutico , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , Vasodilatação/efeitos dos fármacosRESUMO
To overcome drug resistance, the combination of two or more therapeutic strategies with different mechanisms has received much attention in recent years. In this study, a common approach has been used to process curcumin and Zn2+ into colloidal dispersions known as "nanoparticles", which are cheap and easy to prepare with high reproducibility. This novel vehicle has good biocompatibility and high cellular uptake for simultaneously delivering the curcumin drug and siRNA into tumor cells. Complexation of Zn2+ with curcumin enhances the aqueous solubility of the hydrophobic drug curcumin and further improves the cellular uptake and bioavailability. The acid-labile coordination Zn(ii)-O bond in Zn(ii)-curcumin drug nanoparticles (Zn(ii)-Cur NPs) can respond to tumor intracellular acidic pH environments to release curcumin, and promoting acid-triggered intracellular drug release. The positively charged Zn(ii)-Cur NPs can efficiently deliver siRNA into human bladder cancer cells, protect siRNA against enzymatic degradation, and facilitate the escape of loaded siRNA from the endosome into the cytoplasm, which successfully downregulates the targeted EIF5A2 oncogene and consequently inhibits cancer cell growth in vitro and in vivo. Proliferation and migration of cancer cells are inhibited by silencing the expression of EIF5A2 and increasing the ratio of pro-apoptotic BAX to anti-apoptotic BCL-2. In vitro and in vivo experiments have demonstrated that bifunctional Zn(ii)-Cur NPs/siEIF5A2 can combine chemotherapy with gene therapy to afford higher therapeutic efficacy than the individual therapeutic protocols.
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IL-8 is a multi-functional pro-inflammatory chemokine, which is highly expressed in cancers, such as ER-negative breast cancer. The present study demonstrates the pervasive role of IL-8 in the malignant progression of ER-negative breast cancer. IL-8 siRNA inhibited proliferation and delayed the G1 to S cell cycle progression in MDA-MB-231 and BT549 cells. IL-8 silencing resulted in the upregulation of the CDK inhibitor p27, the downregulation of cyclin D1, and the reduction of phosphorylated-Akt and NF-κB activities. IL-8 depletion also increased the chemosensitivity to docetaxel. These results indicate a role for IL-8 in promoting tumor cell survival and resistance to docetaxel and highlight the potential therapeutic significance of IL-8 depletion in ER-negative breast cancer patients.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Interleucina-8/fisiologia , Taxoides/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Docetaxel , Feminino , Humanos , Integrina beta3/genética , Interleucina-8/genética , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno/genéticaRESUMO
AIM: To investigate whether XRCC1 and ADPRT polymorphisms might be associated with outcomes of breast cancer. METHODS: A prospective study was conducted with a total of 335 breast cancer patients undergoing chemotherapy consecutively collected from Jan. 2005 to Jan. 2008. Genotyping of XRCC1 and ADPRT polymorphisms was conducted by PCR-RFLP assay. RESULTS: All 335 patients were followed up until death or the end of Jan. 2012, with a median follow-up period of 38.8 (2-64) months. It was shown that the variant genotype of XRCC1 399Gln/Gln was strongly significantly associated with a decreased risk of death from breast cancer, with an HR (95% CI) of 0.52 (0.28-0.91). Similarly, individuals carrying the ADPRT 762Ala/Ala demonstrated longer survival compared to ADPRT 762 Val/ Val, with an HR (95% CI) of 0.58 (0.31-0.97). Individuals with combination genotypes of XRCC1 399Gln allele and ADPRT 762Ala/Ala presented with a longer survival, the HR (95% CI) being 0.56 (0.32-0.97). CONCLUSION: We found a significant association between XRCC1399Gln/ Gln and ADPRT 762Ala/Ala polymorphisms and clinical outcomes. These two genotypes could be used as a surrogate markers of clinical outcome in glioma cases receiving chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Proteínas de Ligação a DNA/genética , Poli(ADP-Ribose) Polimerases/genética , Polimorfismo Genético/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Poli(ADP-Ribose) Polimerase-1 , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
OBJECTIVES: Compared with Western countries, the incidence rates for breast cancer in China are still low. However, breast cancer appears to be hitting Chinese women at a much younger age, with a peak between 40 and 50 years. Furthermore, breast tumors of Asian women have molecular and genetic characteristics that are different from those of Caucasian women. METHODS: A community-based study was designed to evaluate the relationship between lifestyles and breast cancer risk in Chinese women residing in Guangzhou. 16,314 subjects completed the questionnaire. Potential confounding factors included sociodemographic characteristics. RESULTS: 33 individuals reported a history of breast cancer, yielding a prevalence rate of 202.3/100000. Associations between subjects'demographic and breast cancer risk factors were assessed. Breast cancer is associated with family history of breast cancer, X-rays received, benign breast disease and hyperlipoidemia or hypercholesteremia with elevated odds ratios. CONCLUSIONS: Family history of breast cancer, X-ray received benign breast disease and hyperlipoidemia or hypercholesteremia were significantly associated with risk of breast cancer and may have potential for breast cancer risk assessment.
Assuntos
Neoplasias da Mama/epidemiologia , Estilo de Vida , Adolescente , Adulto , Idoso , China/epidemiologia , Saúde da Família , Feminino , Humanos , Hipercolesterolemia/complicações , Hiperlipidemias/complicações , Pessoa de Meia-Idade , Doses de Radiação , Risco , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To compare clinical curative effects of open surgery (OS) or endovascular repair (EVAR) for patients with abdominal aortic aneurysm (AAA) in China. DATA SOURCES: We performed a comprehensive search of both English and Chinese literatures involving case studies on retrograde OS or EVAR of AAA in China from January 1976 to December 2010. STUDY SELECTION: According to the inclusion criteria, 76 articles were finally analyzed to compare patient characteristics, clinical success, complications, and prognosis. RESULTS: We analyzed a total of 2862 patients with 1757 undergoing OS (OS group) and 1105 undergoing EVAR (EVAR group). There was no significant difference in the success rate of the procedures. Operative time, length of ICU stay, fasting time, duration of total postoperative stay, blood loss, and blood transfusion requirements during the procedure were significantly lower in the EVAR group. A 30-day follow up revealed more cardiac, renal, pulmonary, and visceral complications in the OS group (P < 0.01). Low-limb ischemia, however, was more common in the EVAR group (P < 0.05). The 30-day mortality rate, including aorta-related and non-aorta related mortality, was significantly lower in the EVAR group (P < 0.01). In the follow-up period, there were more patients with occlusions of artificial vessel and late endoleak in the EVAR group (P < 0.01). The overall late mortality rate was higher in the OS group (P < 0.01), especially non-aorta-related late mortality and mortality during the fourth to the sixth year (P < 0.01). CONCLUSIONS: EVAR was safer and less invasive for AAA patients. Patients suffered fewer complications and recovered sooner. However, complications such as artificial vessel occlusion, low-limb ischemia, and endoleak were common in EVAR. Clinicians should carry out further research to solve these complications and improve the efficacy of EVAR.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/métodos , Idoso , China , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients' beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients' persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8% for the standard treatment group and the standard treatment plus patient support program group, respectively (P=0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P=0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P=0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio=3.9; 95% CI, 1.1-13.7; P=0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients' persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Nitrilas/uso terapêutico , Cooperação do Paciente/estatística & dados numéricos , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/patologia , Relações Médico-Paciente , Pós-Menopausa , Padrões de Prática Médica , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The relationship between Epstein-Barr virus (EBV) and breast cancer (BC) is controversial. Interleukin-10 (IL-10) and interferon-γ (IFN-γ) are believed to play a critical role in the host's responses to EBV infection, and their genetic variations may modify the association of EBV with BC risk. METHODS: We examined serum levels of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) and nuclear antigen-1 (EBNA-1) IgA along with the polymorphisms of IL-10 rs1800871 and IFN-γ rs2069705 in 354 incident BC cases and 504 age-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. RESULTS: VCA IgA and EBNA-1 IgA levels were positively associated with BC risk. IL-10 rs1800871 (TC/CC) was associated with a reduced BC risk (OR, 0.74 [95% CI, 0.55-1.00]) but had no interaction with EBV infection on BC risk. IFN-γ rs2069705 was not directly associated with BC risk but interacted with EBNA-1 IgA on BC risk. Among women with the CC genotype, EBNA-1 IgA seropositivity significantly increased the risk of BC compared to EBNA-1 IgA seronegativity (OR, 5.14 [95% CI, 1.76-14.98]). CONCLUSIONS: These results suggest that EBV may contribute to the risk of BC and that this contribution may be modified by genetic variations in IFN-γ.
Assuntos
Anticorpos Antivirais/sangue , Neoplasias da Mama/virologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/imunologia , Imunoglobulina A/sangue , Interferon gama/genética , Interleucina-10/genética , Adulto , Idoso , Neoplasias da Mama/genética , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Vascular anomalies are common and multidisciplinary involved diseases. The greatest impediment to their treatment in the past was their confusing terminology and clinical heterogeneities. This hospital-based retrospective study assessed some clinical characteristics, diagnosis, therapies and outcomes of patients with vascular anomalies in southeast China. METHODS: A total of 592 vascular anomalies patients (patients with intracranial tissues or viscera involved were excluded), admitted to the First Affiliated Hospital of Sun Yat-sen University from January 2006 to September 2009, were enrolled in the study. Data for clinical characteristics, diagnosis, therapies and outcomes were collected and analyzed. RESULTS: Of the 592 patients, the male:female ratios in the vascular tumor group (n = 187) and the vascular malformation group (n = 405) were 1:1.49 and 1:1.06 respectively, with no significant difference between them. The mean onset age of the vascular tumor group was significantly younger than that of the vascular malformation group (p < 0.001). The head and neck were the most commonly (31.4%) involved areas in vascular anomalies. A total of 23.8% of the patients with vascular anomalies had definite symptoms caused by the vascular lesions. In the vascular tumor group, 94.1% of them were infantile hemangiomas. Venous malformation was the most common (41.0%) subtype of vascular malformations. Surgical therapy was undertaken in 94.2% of the patients with vascular anomalies. Of the 519 patients available for the 16 - 58 month follow-up, 322 patients (62.0%) were cured, 108 patients (20.8%) were markedly improved, 57 patients (11.0%) were partially improved, and 32 patients (6.2%) were uncured. CONCLUSIONS: Vascular anomalies are clinically heterogeneous. While the outcome is generally favorable, further effort should be made to determine the appropriate terminology and management.