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1.
Mater Today Bio ; 26: 101074, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38736613

RESUMO

The mechanical environment of vascular endothelial cells (ECs) encompasses a wide range of curvatures due to variations in blood vessel diameters. Integrins, key mediators of cell-matrix interactions, establish connections between the extracellular matrix and the actin cytoskeleton, influencing diverse cellular behaviors. In this study, we explored the impact of spatial confinement on human umbilical vein ECs (HUVECs) cultured within three-dimensional hydrogel microgrooves of varying curvatures and the underlying role of integrins in mediating cellular responses. Employing maskless lithography, we successfully fabricated precise and wall curvatures-controlled hydrogel microgrooves, conferring spatial constraints on the cells. Our investigations revealed substantial alterations in HUVEC behavior within the hydrogel microgrooves with varying sidewall curvatures, marked by reduced cell size, enhanced orientation, and increased apoptosis. Interestingly, microgroove curvature emerged as a crucial factor influencing cell orientation and apoptosis, with rectangular microgrooves eliciting distinct changes in cell orientation, while ring-form microgrooves exhibited higher apoptosis rates. The side-wall effect in the 20 µm region near the microgroove wall had the greatest influence on cell orientation and apoptosis. HUVECs within the microgrooves exhibited elevated integrin expression, and inhibition of αV-integrin by cilengitide significantly curtailed cell apoptosis without affecting proliferation. Additionally, integrin-mediated cell traction force closely correlated with the spatial confinement effect. Cilengitide not only reduced integrin and focal adhesion expression but also attenuated cell traction force and cytoskeletal actin filament alignment. Overall, our findings elucidate the spatial confinement of ECs in hydrogel microgrooves and underscores the pivotal role of integrins, particularly αV-integrin, in mediating cell traction force and apoptosis within this microenvironment.

2.
Radiat Oncol ; 18(1): 200, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38098106

RESUMO

BACKGROUND: Breast cancer is the most widespread cancer in women and young women worldwide. Moving towards customised radiotherapy, balancing the use of the available technology with the best treatment modality may not be an easy task in the daily routine. This study aims to evaluate the effectiveness of introducing IQ-feasibility into clinical practice to support the decision of free-breathing (FB) versus breath-hold (BH) left-sided breast irradiations, in order to optimise the technology available and the effectiveness of the treatment. METHODS: Thirty-five patients who received 3D radiotherapy treatment of the left breast in deep-inspiration BH were included in this retrospective study. Computed tomography scans in FB and BH were acquired for each patient; targets contoured in both imaging datasets by an experienced radiation oncologist, and organs at risk delineated using automatic segmentation software were exported to PlanIQ™ (Sun Nuclear Corp.) to generate feasibility dose volume histogram (FDVHs). The dosimetric parameter of BH versus FB FDVH, and BH clinical dataset versus BH FDVH were compared. RESULTS: A total of 30 patients out of 35 patients analysed, presented for the BH treatments a significant reduction (p < 0.05) in the heart mean dose ([Formula: see text]), volume receiving 5 Gy ([Formula: see text]) and 20 Gy ([Formula: see text]), of 35.7%, 54.5%, and 2.1%, respectively; for the left lung, a lower reduction was registered and significant only for [Formula: see text] (21.4%, p = 0.046). For the remaining five patients, the FDVH cut-off points of heart and lung were superimposable with differences of less than 1%. Heart and left lung dosimetric parameters of the BH clinical plans are located in the difficult zone of the FDVH and differ significantly (p < 0.05) from the corresponding parameters of the FDVH curves delimiting this buffer area between the impossible and feasible zones, respectively. CONCLUSION: The use of PlanIQTM as a decision-support tool for the FB versus BH treatment delivery modality allows customisation of the treatment technique using the most appropriate technology for each patient enabling accurate management of available technologies.


Assuntos
Neoplasias da Mama , Neoplasias Unilaterais da Mama , Feminino , Humanos , Suspensão da Respiração , Estudos Retrospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Respiração , Neoplasias da Mama/radioterapia , Coração/efeitos da radiação , Neoplasias Unilaterais da Mama/radioterapia , Órgãos em Risco/efeitos da radiação
3.
Radiat Oncol ; 18(1): 136, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592338

RESUMO

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgART) treatment sessions at MR-Linac are time-consuming and changes in organs at risk volumes can impact the treatment dosimetry. This study aims to evaluate the feasibility to control bladder filling during the rectum MRgART online session and its effectiveness on plan dosimetry. METHODS: A total of 109 online adaptive sessions of 24 rectum cancer patients treated at Unity 1.5 T MR-Linac with a short course radiotherapy (25 Gy, 5 Gy × 5) for whom the adaptive plan was optimized and recalculated online based on the daily magnetic resonance imaging (MRI) were analysed. Patients were fitted with a bladder catheter to control bladder filling; the bladder is emptied and then partially filled with a known amount of saline at the beginning and end of the online session. A first MRI ([Formula: see text]) acquired at the beginning of the session was used for plan adaptation and the second ([Formula: see text]) was acquired while approving the adapted plan and rigidly registered with the first to ensure the appropriateness of the isodoses on the ongoing delivery treatment. For each fraction, the time interval between the two MRIs and potential bladder changes were assessed with independent metrics, and the impact on the plan dosimetry was evaluated by comparing target and organs at risk dose volume histogram cut-off points of the plan adapted on [Formula: see text] and recalculated on [Formula: see text]. RESULTS: Median bladder volume variations, DSC, and HD of 8.17%, 0.922, and 2.92 mm were registered within a median time of 38 min between [Formula: see text] and [Formula: see text]; dosimetric differences < 0.65% were registered for target coverage, and < 0.5% for bladder, small bowel and femoral heads constraints, with a p value > 0.05. CONCLUSION: The use of a bladder filling control procedure can help ensure the dosimetric accuracy of the online adapted treatment delivered.


Assuntos
Radioterapia (Especialidade) , Radioterapia Guiada por Imagem , Neoplasias Retais , Humanos , Bexiga Urinária , Neoplasias Retais/radioterapia , Imageamento por Ressonância Magnética
4.
Front Physiol ; 14: 1199225, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37389120

RESUMO

Tumour progression and metastasis remain the leading causes of cancer-related death worldwide. Tumour angiogenesis is essential for tumour progression. The vasculature surrounding tumours is not only a transport channel for nutrients, oxygen, and metabolites, but also a pathway for metastasis. There is a close interaction between tumour cells and endothelial cells in the tumour microenvironment. Recent studies have shown that tumour-associated endothelial cells have different characteristics from normal vascular endothelial cells, play an important role in tumour progression and metastasis, and are expected to be a key target for cancer therapy. This article reviews the tissue and cellular origin of tumour-associated endothelial cells and analyses the characteristics of tumour-associated endothelial cells. Finally, it summarises the role of tumour-associated endothelial cells in tumour progression and metastasis and the prospects for their use in clinical anti-angiogenic therapy.

5.
Yale J Biol Med ; 96(4): 527-547, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38161579

RESUMO

Micropatterns, characterized as distinct physical microstructures or chemical adhesion matrices on substance surfaces, have emerged as a powerful tool for manipulating cellular activity. By creating specific extracellular matrix microenvironments, micropatterns can influence various cell behaviors, including orientation, proliferation, migration, and differentiation. This review provides a comprehensive overview of the latest advancements in the use of micropatterns for cell behavior regulation. It discusses the influence of micropattern morphology and coating on cell behavior and the underlying mechanisms. It also highlights future research directions in this field, aiming to inspire new investigations in materials medicine, regenerative medicine, and tissue engineering. The review underscores the potential of micropatterns as a novel approach for controlling cell behavior, which could pave the way for breakthroughs in various biomedical applications.


Assuntos
Células Cultivadas , Humanos , Diferenciação Celular
6.
Front Oncol ; 12: 920443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36106119

RESUMO

Adaptive radiotherapy performed on the daily magnetic resonance imaging (MRI) is an option to improve the treatment quality. In the adapt-to-shape workflow of 1.5-T MR-Linac, the contours of structures are adjusted on the basis of patient daily MRI, and the adapted plan is recalculated on the MRI-based synthetic computed tomography (syCT) generated by bulk density assignment. Because dosimetric accuracy of this strategy is a priority and requires evaluation, this study aims to explore the usefulness of adding an assessment of dosimetric errors associated with recalculation on syCT to the clinical workflow. Sixty-one patients, with various tumor sites, treated using a 1.5-T MR-Linac were included in this study. In Monaco V5.4, the target and organs at risk (OARs) were contoured, and a reference CT plan that contains information about the outlined contours, their average electron density (ED), and the priority of ED assignment was generated. To evaluate the dosimetric error of syCT caused by the inherent approximation within bulk density assignment, the reference CT plan was recalculated on the syCT obtained from the reference CT by forcing all contoured structures to their mean ED defined on the reference plan. The dose-volume histogram (DVH) and dose distribution of the CT and syCT plan were compared. The causes of dosimetric discrepancies were investigated, and the reference plan was reworked to minimize errors if needed. For 54 patients, gamma analysis of the dose distribution on syCT and CT show a median pass rate of 99.7% and 98.5% with the criteria of 3%/3 mm and 2%/2 mm, respectively. DVH difference of targets and OARs remained less than 1.5% or 1 Gy. For the remaining patients, factors (i.e., inappropriate ED assignments) influenced the dosimetric agreement of the syCT vs. CT reference DVH by up to 21%. The causes of the errors were promptly identified, and the DVH dosimetry was realigned except for two lung treatments for which a significant discrepancy remained. The recalculation on the syCT obtained from the planning CT is a powerful tool to assess and decrease the minimal error committed during the adaptive plan on the MRI-based syCT.

7.
Front Cell Dev Biol ; 10: 816698, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813192

RESUMO

Extracellular vesicles (EVs) are vesicles with a lipid bilayer membrane on the outside, which are widely found in various body fluids and contain biological macromolecules such as DNA, RNA, lipids and proteins on the inside. EVs were once thought to be vesicles for the removal of waste materials, but are now known to be involved in a variety of pathophysiological processes in many diseases. This study examines the advantage of EVs and the challenges associated with their application. A more rational use of the advantageous properties of EVs such as composition specificity, specific targeting, circulatory stability, active penetration of biological barriers, high efficient drug delivery vehicles and anticancer vaccines, oxidative phosphorylation activity and enzymatic activity, and the resolution of shortcomings such as isolation and purification methods, storage conditions and pharmacokinetics and biodistribution patterns during drug delivery will facilitate the clinical application of EVs.

8.
J Biomech ; 131: 110917, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34952348

RESUMO

Cell death of endothelial cells (ECs) is a common devastating consequence of various vascular-related diseases. Atherosclerosis, hypertension, sepsis, diabetes, cerebral ischemia and cardiac ischemia/reperfusion injury, and chronic kidney disease remain major causes of morbidity and mortality worldwide, in which ECs are constantly subjected to a great amount of dynamic changed mechanical forces including shear stress, extracellular matrix stiffness, mechanical stretch and microgravity. A thorough understanding of the regulatory mechanisms by which the mechanical forces controlled the cell deaths including apoptosis, autophagy, and pyroptosis is crucial for the development of new therapeutic strategies. In the present review, experimental and clinical data highlight that nutrient depletion, oxidative stress, tumor necrosis factor-α, high glucose, lipopolysaccharide, and homocysteine possess cytotoxic effects in many tissues and induce apoptosis of ECs, and that sphingosine-1-phosphate protects ECs. Nevertheless, EC apoptosis in the context of those artificial microenvironments could be enhanced, reduced or even reversed along with the alteration of patterns of shear stress. An appropriate level of autophagy diminishes EC apoptosis to some extent, in addition to supporting cell survival upon microenvironment challenges. The intervention of pyroptosis showed a profound effect on atherosclerosis. Further cell and animal studies are required to ascertain whether the alterations in the levels of cell deaths and their associated regulatory mechanisms happen at local lesion sites with considerable mechanical force changes, for preventing senescence and cell deaths in the vascular-related diseases.


Assuntos
Aterosclerose , Células Endoteliais , Animais , Apoptose , Estresse Oxidativo , Estresse Mecânico
9.
Technol Cancer Res Treat ; 20: 15330338211062429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855575

RESUMO

Objectives: In breast radiotherapy, the proximity of the target to sensitive structures together with the uncertainty introduced by respiratory movement, make this treatment one of the most studied to increase its effectiveness. Dosimetric and physical variables play an important role and the study of their correlation and impact on treatment is fundamental. This retrospective study aims to highlight the dosimetric differences of 2 different clinical data sets of patients receiving left-sided breast irradiation in free breathing (FB) or breath hold (BH). Methods: A total of 155 left breast carcinoma patients receiving whole-breast irradiation in FB (73 patients) and BH (82 patients) were enrolled in this study. The dosimetric parameters of the target, heart, left and right lung and right breast were evaluated and compared, and possible correlations were studied in both groups. Results: No significant difference (P > .05) was found in the target dosimetry; a clear advantage in BH for both high and low doses received by the heart, with reductions of the dosimetric parameters between 27.1% and 100% (P < .003); for the left lung reductions decreased with increasing dose (-22.4% and -13.4% for doses of 5 and 20 Gy, respectively, P < .003). Conclusion: Significant correlations for BH treatments were registered between the volumes of the target and left lung, and the dosimetric parameters of the heart and left lung. BH treatment brings significant dosimetric advantages to organs at risk for a wide range of patients with different anatomy, target volumes and lung capacity, with additional benefits for small-sized breasts and important lung capacity.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Tratamentos com Preservação do Órgão/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Suspensão da Respiração , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Órgãos em Risco , Radiometria , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/métodos , Respiração , Estudos Retrospectivos , Adulto Jovem
10.
Aging (Albany NY) ; 13(8): 12031-12045, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888646

RESUMO

Dysfunction of bone marrow mesenchymal stem cells (BMSCs), osteoblasts and osteocytes may be one of the main causes of bone loss in the elderly. In the present study, we found osteogenic cells from aged rats all exhibited senescence changes, with the most pronounced senescence changes in osteocytes. Meanwhile, the proliferative capacity and functional activity of osteogenic cells from aged rats were suppressed. Osteogenic differentiation capacity of BMSCs from aged rats decreased while adipogenic capacity increased. The mineralization capacity, ALP activity and osteogenic proteins expression of osteoblasts from aged rats decreased. Additionally, osteocytes from aged rats up-expressed sclerosteosis protein, a negative regulator of bone formation. To inhibit osteogenic cell senescence, we use low magnitude vibration (LMV) to eliminate the senescent osteogenic cells. After LMV treatment, the number of osteogenic cells staining positively for senescence-associated-ß-galactosidase (SA-ß-Gal) decreased significantly. Besides, the expression of anti-aging protein SIRT1 was upregulated significantly, while p53 and p21 were downregulated significantly after LMV treatment. Thus, the LMV can inhibit the senescence of osteogenic cells partly through the Sirt1/p53/p21 axis. Furthermore, LMV was found to promote bone formation of aged rats. These results suggest that the inhibition of osteogenic cell senescence by LMV is a valuable treatment to prevent or delay osteoporosis.


Assuntos
Osteogênese/fisiologia , Osteoporose/terapia , Vibração/uso terapêutico , Animais , Células Cultivadas , Senescência Celular/fisiologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Osteoblastos/fisiologia , Osteoporose/fisiopatologia , Cultura Primária de Células , Ratos , Sirtuína 1/genética , Proteína Supressora de Tumor p53/genética , Regulação para Cima/fisiologia
11.
Front Cell Dev Biol ; 8: 755, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850858

RESUMO

We previously demonstrated that vascular endothelial cells released VEGF-enriched exosomes to promote the tumor vasculogenesis and progression after anti-angiogenic therapies (AATs). To clarify how microRNA (miR)-9 promoted the angiogenesis of tumor-associated endothelial cells, in the present study, we investigated the association between miR-9 and sphingosine-1-phosphate (S1P) receptors in angiogenesis. The levels of miR-9 and S1P receptors in normal and tumor endothelial cells were compared with EndoDB database and their correlations were analyzed. The levels of S1P1, S1P2, and S1P3 were detected in miR-9 overexpressing endothelial cells by qRT-PCR and western blot. The binding sites of miR-9 on S1P1 and S1P3 were predicted and tested by dual-luciferase reporter assays. Then, angiogenesis in endothelial cells overexpressing both S1P1 and miR-9 was detected. The results showed that miR-9 is overexpressed in ECs from medulloblastoma and glioblastoma xenograft, which is negatively associated with S1P1 and S1P3. Overexpression of miR-9 significantly inhibited S1P1 and S1P3 in both mRNA and protein levels. We predicted that binding sites exist between miR-9 and S1P1, S1P3, but only S1P1 was directly targeted by miR-9. Overexpression of S1P1 significantly suppressed the miR-9-induced angiogenesis. Therefore, miR-9 induces angiogenesis via targeting on S1P1.

12.
Radiat Oncol ; 15(1): 103, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381103

RESUMO

BACKGROUND: Volumetric modulated arc therapy (VMAT) adopted in post-mastectomy radiation therapy (PMRT) has the capacity to achieve highly conformal dose distributions. The research aims to evaluate the impact of positioning errors in the dosimetry of VMAT left-sided PMRT. METHODS: A total of 18 perturbations where introduced in 11 VMAT treatment plans that shifted the isocenter from its reference position of 3, 5, 10 mm in six directions. The thoracic wall and supraclavicular clinical target volumes (CTVs), the heart and the left lung dose volume histograms (DVHs) of 198 perturbed plans were calculated. The absolute differences (∆) of the mean dose (Dm) and DVH endpoints Vx and Dy (percentage volume receiving x Gy, and dose covering y% of the volume, respectively) were used to compare the dosimetry of the reference vs perturbed plans. RESULTS: Isocenter shifts in the anterior and lateral directions lead to maximum disagreement between the CTVs dosimetry of perturbed vs reference plans. Isocenter shifts of 10 mm shown a decrease of D95, D98 and Dm of 12.8, 18.0, and 2.9% respectively, for the CTVs. For 5 mm isocenter shifts, these differences decreased to 3.2, 5.2, and 0.9%, respectively, and for 3 mm shifts to 1.0, 1.7, and 0.6%, respectively. For the organs at risk (OARs), only isocenter shifts in the right, posterior and inferior directions worsen the plan dosimetry, nevertheless not negligible lung ∆ V20 of + 2.6%, and heart ∆ V25 of + 1.6% persist for 3 mm shifts. CONCLUSIONS: Inaccuracy in isocenter positioning for VMAT left-sided PMRT irradiation may impact the dosimetry of the CTVs and OARs to a different extent, depending on the directions and magnitude of the perturbation. The acquired information could be useful for planning strategies to guarantee the accuracy of the treatment delivered.


Assuntos
Posicionamento do Paciente/efeitos adversos , Radioterapia Adjuvante/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Feminino , Humanos , Mastectomia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Neoplasias Unilaterais da Mama/cirurgia
13.
J Extracell Vesicles ; 8(1): 1629865, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258881

RESUMO

Although anti-angiogenic therapies (AATs) have some effects against multiple malignancies, they are limited by subsequent tumor vasculogenesis and progression. To investigate the mechanisms by which tumor vasculogenesis and progression following AATs, we transfected microRNA (miR)-9 into human umbilical vein endothelial cells (HUVECs) to mimic the tumor-associated endothelial cells in hepatocellular carcinoma and simulated the AATs in vitro and in vivo. We found that administration of the angiogenesis inhibitor vandetanib completely abolished miR-9-induced angiogenesis and promoted autophagy in HUVECs, but induced the release of vascular endothelial growth factor (VEGF)-enriched exosomes. These VEGF-enriched exosomes significantly promoted the formation of endothelial vessels and vasculogenic mimicry in hepatocellular carcinoma and its progression in mice. Anti-autophagic therapy is proposed to improve the efficacy of AATs. However, similar effects by AATs were observed with the application of anti-autophagy by 3-methyladenine. Our results revealed that tumor vasculogenesis and progression after AATs and anti-autophagic therapies were due to the cross-talk between endothelial and tumor cells via VEGF-enriched exosomes.

14.
Technol Cancer Res Treat ; 17: 1533033818803582, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30343642

RESUMO

Acute skin toxicity observed in radiotherapy treatment of head and neck cancer is a big concern. The purpose of this work is to evaluate the feasibility of a skin dose reduction in the treatment of nasopharyngeal carcinoma without compromising the overall plan quality. This research focused on comparison of the skin dose reduction that can be obtained for the main high conformal radiotherapy delivery techniques. Sixteen cases of early-stage nasopharyngeal carcinoma were included in this study. For each case, a dynamic intensity-modulated radiation therapy, a volumetric modulated arc therapy, and a helical tomotherapy treatment plans were performed with and without the skin as a sensitive structure in the inverse plan optimization. The dosimetric results obtained for the different treatment techniques and plan optimizations were compared. Dose-volume histogram cutoff points of D95%, D98%, and the homogeneity index were used for target comparison, while Dmean and Dmax/D1cc were used for the organs at risk. The skin volume receiving 5 Gy and then 10 to 70 Gy of radiation dosage registered at step of 10 Gy and Dmean were used for the skin dose comparison. One-way analysis of variance was used to assess the dosimetric results obtained for the different types of treatment plans and techniques investigated. A total of 96 treatment plans were analyzed. When the neck skin was considered in the treatment optimization process, the skin volume that received more than 30 Gy was reduced by 3.7% for dynamic intensity modulated, 4.1% for volumetric modulated arc, and 4.3% for dynamic intensity modulated, while the target dose coverage and organs at risk dosages remained unvaried ( p > .05).


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Órgãos em Risco , Radioterapia de Intensidade Modulada , Pele/efeitos da radiação , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Lesões por Radiação , Radiometria , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
15.
Oncotarget ; 7(39): 63324-63337, 2016 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-27556509

RESUMO

Sphingosine-1-phosphate (S1P) induces epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC). However, its underlying mechanism remains largely unknown. In the present study, we investigated the correlation between S1P and syndecan-1 in HCC, the molecular mechanism involved, as well as their roles in EMT of HCC. Results revealed a high serum S1P level presents in patients with HCC, which positively correlated with the serum syndecan-1 level. A significant inverse correlation existed between S1P1 and syndecan-1 in HCC tissues. S1P elicits activation of the PI3K/AKT signaling pathways via S1P1, which triggers HPSE, leading to increases in expression and activity of MMP-7 and leading to shedding and suppression of syndecan-1. The loss of syndecan-1 causes an increase in TGF-ß1 production. The limited chronic increase in TGF-ß1 can convert HCC cells into a mesenchymal phenotype via establishing an MMP-7/Syndecan-1/TGF-ß autocrine loop. Finally, TGF-ß1 and syndecan-1 are essential for S1P-induced epithelial to mesenchymal transition. Taken together, our study demonstrates that S1P induces advanced tumor phenotypes of HCC via establishing an MMP-7/syndecan-1/TGF-ß1 autocrine loop, and implicates targetable S1P1-PI3K/AKT-HPSE-MMP-7 signaling axe in HCC metastasis.


Assuntos
Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Lisofosfolipídeos/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Esfingosina/análogos & derivados , Sindecana-1/metabolismo , Idoso , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Transdução de Sinais , Esfingosina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
16.
Oncol Lett ; 12(1): 379-382, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27347154

RESUMO

The developmental process of epithelial-mesenchymal transition (EMT) occurs when epithelial cells acquire invasive mesenchymal cell characteristics, and the activation of this process has been indicated to be involved in tumor progression. EMT could be induced by growth factors, cytokines and matrix metalloproteinases (MMPs). sphingosine-1-phosphate (S1P) is a biologically-active lipid that plays an important role in cancer metastasis. S1P also contributes to the activation of EMT. However, the mechanism underlying S1P-induced EMT is unclear. Increased evidence has demonstrated that the cell surface glycocalyx is closed associated with S1P and plays an important role in tumor progression, suggesting that S1P-induced EMT could be Snail-MMP signaling-dependent. Thus, we hypothesize that an S1P-glycocalyx-Snail-MMP signaling axis mediates S1P-induced EMT. This is an essential step towards improved understanding of the underlying mechanism involved in S1P-regulted EMT, and the development of novel diagnostic and anticancer therapeutic strategies.

17.
Int J Mol Med ; 36(6): 1639-47, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26459744

RESUMO

Acute ischemic stroke is a significant cause of high morbidity and mortality in the aging population globally. However, current therapeutic strategies for acute ischemic stroke are limited. Atherosclerotic plaque is considered an independent risk factor for acute ischemic stroke. To identify biomarkers for carotid atheromatous plaque, bioinformatics analysis of the gene microarray data of plaque and intact tissue from individuals was performed. Differentially expressed genes (DEGs) were identified using the Multtest and Limma packages of R language, including 56 downregulated and 69 upregulated DEGs. Enriched microRNA (miRNA or miR) DEGs networks were generated using WebGestalt software and the STRING databases, and the miRNAs were validated using serum from acute ischemic stroke patients with reverse transcription quantitative PCR (RT­qPCR). Four confirmed differentially expressed miRNAs (miR­9, ­22, ­23 and ­125) were associated with 28 upregulated DEGs, and 7 miRNAs (miR­9, ­30, ­33, ­124, ­181, ­218 and ­330) were associated with 25 downregulated DEGs. Gene ontology (GO) function suggested that the confirmed miRNA­targeted DEGs predominantly associated with signal transduction, the circulatory system, biological adhesion, striated muscle contraction, wound healing and the immune system. The confirmed miRNA­targeted genes identified serve as potential therapeutic targets for acute ischemic stroke.


Assuntos
Biomarcadores/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Acidente Vascular Cerebral/genética , Isquemia Encefálica/complicações , Análise por Conglomerados , Bases de Dados Genéticas , Redes Reguladoras de Genes/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Acidente Vascular Cerebral/etiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-22994242

RESUMO

To study the effect of the porous membrane permeability on the hydrodynamics in a parallel-plate coculture flow chamber (PPcFC), we demonstrated the permeability of the porous membrane as a function of some parameters, such as porosity, membrane thickness, pore size and shape of the membrane. The effect of permeability on the flow in the PPcFC was analysed using the commercial software - Fluent. Results showed that the permeability was directly proportional to the thickness, the porosity and the pore size of the membrane, and inversely proportional to the surface shape factor. To ensure the best flow pattern, the inlet velocity range was limited by the membrane permeability and fluid viscosity, and then restricted the available magnitudes of shear rate on the permeable membrane. Our findings are helpful in designing and preparing the biomaterials that have adequate mechanical properties for the functional vascular grafts production, and in using of the flow chamber in various investigations.


Assuntos
Técnicas de Cocultura , Simulação por Computador , Materiais Biocompatíveis , Hidrodinâmica , Permeabilidade , Porosidade , Viscosidade
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