Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.605
Filtrar
1.
Med Oncol ; 36(11): 95, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637536

RESUMO

Ovarian cancer is one of the most lethal gynecological cancers; owning to its late detection and chemoresistance, understanding the pathogenesis of this malignant tumor is much critical. Previous studies have reported that ubiquitin-specific peptidase 39 (USP39) is generally overexpressed in a variety of cancers, including hepatocellular carcinoma, gastric cancer and so forth. Furthermore, USP39 is proved to be associated with the proliferation of malignant tumors. However, the function and mechanism of USP39 in ovarian cancer have not been elucidated. In the present study, we observed that USP39 was frequently overexpressed in human ovarian cancer and was highly correlated with TNM stage. Suppression of USP39 markedly inhibited the growth and migration of ovarian cancer cell lines HO-8910 and SKOV3 and induced cell cycle G2/M arrest. Moreover, knockdown of USP39 inhibited ovarian tumor growth in a xenograft model. In addition, our findings indicated that cell cycle arrest induced by USP39 knockdown might be involved in p53/p21 signaling pathway. Furthermore, we found that the depletion of USP39 inhibited the migration of ovarian cancer cells via blocking epithelial-mesenchymal transition. Taken together, these results suggest that USP39 may play vital roles in the genesis and progression and may serve as a potential biomarker for diagnosis and therapeutic target of ovarian cancer.


Assuntos
Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Proteína Supressora de Tumor p53/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Animais , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Transição Epitelial-Mesenquimal , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular , Técnicas de Silenciamento de Genes , Células HEK293 , Xenoenxertos , Humanos , Imuno-Histoquímica , Pontos de Checagem da Fase M do Ciclo Celular , Camundongos , Camundongos Nus , Estadiamento de Neoplasias , Neoplasias Ovarianas/enzimologia , Transdução de Sinais , Proteases Específicas de Ubiquitina/biossíntese , Proteases Específicas de Ubiquitina/genética
2.
Cancer Discov ; 9(10): 1340-1342, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31575562

RESUMO

Effective options are limited for patients with small-cell lung cancer who develop progressive disease during or after etoposide plus platinum-based therapy. In this issue of Cancer Discovery, Farago and colleagues highlight the data for temozolomide plus olaparib in this patient population and demonstrate the potential to accelerate biomarker discovery through co-clinical trials utilizing patient-derived xenografts.See related article by Farago et al., p. 1372.


Assuntos
Neoplasias Pulmonares , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Biomarcadores , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Recidiva Local de Neoplasia , Ftalazinas , Piperazinas , Temozolomida , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Anticancer Res ; 39(9): 4711-4720, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519570

RESUMO

BACKGROUND/AIM: Dynamics of circulating tumor cells (CTCs) after molecular targeting therapy remain unclear. MATERIALS AND METHODS: We examined changes in CTC numbers and morphology early after targeting therapy in EGFR-mutated PC-9 human lung cancer and HER2-gene amplified GLM-1 gastric cancer mouse CTC models using a cytology-based semi-automated CTC detection platform. RESULTS: Erlotinib and T-DM1 inhibited cell growth mainly by induction of apoptosis in vitro. The number of CTCs detected 5-10 days after targeting therapy in mice was significantly increased compared to CTC numbers before therapy. The increased CTCs after therapy consisted of apoptotic CTCs and viable CTCs. This heterogeneous population of CTCs reflects well the cell population of the primary tumor disrupted by therapy. CONCLUSION: CTCs can be mobilized from the primary tumor due to tissue disruption in acute response to targeting therapy, suggesting potential usefulness of CTC monitoring as a predictor of therapeutic response in the clinical settings.


Assuntos
Amplificação de Genes , Mutação , Células Neoplásicas Circulantes/metabolismo , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/tratamento farmacológico
4.
Cancer Res ; 79(17): 4324-4325, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31481418

RESUMO

Patient-derived tumor xenograft (PDX) models are frequently used to study cancer mechanisms and potential therapeutics, however, differences in tumor evolution between models and patients have called into question their clinical relevance. In this issue, Mer and colleagues describe the Xenograft Visualization and Analysis (Xeva) software tool that empowers pharmacogenomic analysis through integration of PDX model tumor-drug response with genetic data. By performing the largest PDX model meta-analysis of its kind, the authors demonstrate PDX models are robust platforms for cancer treatment studies. With a clear need for more integrative studies, Xeva is well placed to make more important contributions to pharmacogenomic discovery.See related article by Mer et al., p. 4539.


Assuntos
Neoplasias , Animais , Modelos Animais de Doenças , Xenoenxertos , Humanos , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Chem Commun (Camb) ; 55(70): 10400-10403, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31402360

RESUMO

We report the first pretargeting in vivo study using the Strain-Promoted Sydnone-Alkyne Cycloaadition (SPSAC) reaction. The injection of a fluorine-18 labeled cyclooctyne three days after cetuximab bearing chlorosydnone moieties allowed a significant detection of the tumor by PET imaging suggesting an efficient click reaction inside the tumoral site. With a kinetic constant superior to 300 M-1 s-1, the SPSAC reaction might be an interesting tool, in addition to tetrazine-cyclooctene ligation, for in vivo chemistry.


Assuntos
Alquinos/química , Química Click/métodos , Radioisótopos de Flúor/química , Tomografia por Emissão de Pósitrons/métodos , Animais , Ciclização , Xenoenxertos , Humanos , Camundongos
7.
Nat Neurosci ; 22(8): 1289-1305, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285612

RESUMO

The effects of autonomic innervation of tumors on tumor growth remain unclear. Here we developed a series of genetic techniques to manipulate autonomic innervation in a tumor- and fiber-type-specific manner in mice with human breast cancer xenografts and in rats with chemically induced breast tumors. Breast cancer growth and progression were accelerated following stimulation of sympathetic nerves in tumors, but were reduced following stimulation of parasympathetic nerves. Tumor-specific sympathetic denervation suppressed tumor growth and downregulated the expression of immune checkpoint molecules (programed death-1 (PD-1), programed death ligand-1 (PD-L1), and FOXP3) to a greater extent than with pharmacological α- or ß-adrenergic receptor blockers. Genetically induced simulation of parasympathetic innervation of tumors decreased PD-1 and PD-L1 expression. In humans, a retrospective analysis of breast cancer specimens from 29 patients revealed that increased sympathetic and decreased parasympathetic nerve density in tumors were associated with poor clinical outcomes and correlated with higher expression of immune checkpoint molecules. These findings suggest that autonomic innervation of tumors regulates breast cancer progression.


Assuntos
Fibras Autônomas Pré-Ganglionares/patologia , Neoplasias da Mama/patologia , Antagonistas Adrenérgicos/farmacologia , Animais , Antígeno B7-H1/genética , Denervação , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/genética , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Sistema Nervoso Parassimpático/patologia , Receptor de Morte Celular Programada 1/genética , Ratos , Estudos Retrospectivos , Estresse Psicológico/psicologia , Sistema Nervoso Simpático/patologia
8.
Molecules ; 24(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288458

RESUMO

BACKGROUND/AIM: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers. METHODS: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model. RESULTS: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively. CONCLUSION: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.


Assuntos
Alpinia/química , Antineoplásicos Fitogênicos/química , Extratos Vegetais/química , Pironas/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Catalase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clorofórmio/química , Flores/química , Xenoenxertos , Humanos , Malondialdeído/metabolismo , Metanol/química , Camundongos , Transplante de Neoplasias , Extratos Vegetais/farmacologia , Plantas Medicinais , Pironas/farmacologia , Solventes , Superóxido Dismutase/metabolismo
9.
Life Sci ; 232: 116649, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301415

RESUMO

AIMS: To investigate the potential biological role of E2F6 and its underlying molecular mechanism in gastric carcinoma (GC) progression. MAIN METHODS: The expressions of cancer susceptibility candidate 2 (CASC2), E2F6 and matrix metalloprotein-2 (MMP-2) were measured by quantitative real-time polymerase chain reaction and western blotting. The inhibitory effect of E2F6 on CASC2 was evaluated using luciferase reporter assay. Cell growth was assessed by colony formation assay and cell counting kit-8. Cell invasion and apoptosis were measured by transwell assay and flow cytometry assay, respectively. In vivo tumorigenicity was assessed by tumor xenografts in nude mice. KEY FINDINGS: Our data revealed that CASC2 was downregulated while E2F6 was upregulated in GC tissues and cell lines. Remarkably, lower expression of CASC2 was associated with poor survival in GC patients. E2F6 inhibited the expression of CASC2. Subsequently, reliable data showed that downregulation of E2F6 suppressed the proliferation and invasion, and promoted the apoptosis of GC cells. Furthermore, downregulation of E2F6 decreased the expression of MMP-2 and increased the activity of caspase-3. However, these changes triggered by E2F6 knockdown could be reversed by inhibition of CASC2. Moreover, we also proved that downregulation of CASC2 reverses the effect of E2F6 knockdown on tumor growth in vivo. SIGNIFICANCE: Our data demonstrated that E2F6 could regulate the proliferation, invasion and apoptosis of GC cells via inhibiting the expression of CASC2, suggesting that E2F6/CASC2 axis is another regulator of GC progression.


Assuntos
Regulação para Baixo/fisiologia , Fator de Transcrição E2F6/fisiologia , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/genética , Animais , Western Blotting , Linhagem Celular Tumoral , Progressão da Doença , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
10.
Gene ; 715: 144015, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31357025

RESUMO

Tripartite Motif Containing 13 (TRIM13), a member of TRIM proteins, is deleted in multiple tumor types, especially in B-cell chronic lymphocytic leukemia and multiple myeloma. The present study explored the expression and potential role of TRIM13 in non-small-cell lung carcinoma (NSCLC). We found that TRIM13 mRNA and protein expression was reduced in NSCLC tissues and cell lines in comparison to paired non-cancerous tissues and a human normal bronchial epithelial cell line, respectively. Overexpression of TRIM13 in NCI-H1975 and SPC-A-1 cells hampered cell proliferation. Additionally, TRIM13 overexpression increased the levels of cleaved caspase-3. TRIM13-induced NSCLC cell apoptosis was attenuated by a caspase-3 inhibitor Ac-DEVD-CHO, suggesting that TRIM13 induced cell apoptosis partially through a caspase-3-dependent pathway. Moreover, it has been reported that TRIM13 can regulate nuclear factor kappaB (NF-κB) activity. Our data showed that TRIM13 overexpression inactivated NF-κB as indicated by the increased cytosolic NF-κB and decreased nuclear NF-κB. Exposure to an NF-κB inhibitor PDTC significantly blocked the impact of TRIM13 knockdown on cell proliferation and apoptosis, indicating the functions of TRIM13 in NSCLC cells were mediated by the NF-κB pathway. Finally, we demonstrated that TRIM13 overexpression suppressed tumor growth and induced cell apoptosis in vivo by using a xenograft mouse model. Collectively, our results indicate that TRIM13 behaves as a tumor suppressor in NSCLC through regulating NF-κB pathway. Our findings may offer a promising therapeutic target for NSCLC.


Assuntos
Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ligação a DNA/genética , Feminino , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , NF-kappa B/genética , Transplante de Neoplasias , Transdução de Sinais , Proteínas Supressoras de Tumor/genética
11.
Life Sci ; 232: 116614, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260682

RESUMO

AIMS: SRY-box 18 (SOX18) is a transcription factor known for its role in regulating cell differentiation and lymphatic and blood vessel development. It has been reported that SOX18 was involved in various diseases, including cancer. This study aimed to explore the significance and biological function of SOX18 in bladder cancer (BCa). MATERIALS AND METHODS: SOX18 expression in BCa and normal tissues was analyzed by immunohistochemistry, and SOX18 expression in BCa cell lines was quantified by western blotting and quantitative real-time PCR. The role of SOX18 on the proliferation, migration and invasion of BCa cells was explored by CCK-8 and transwell invasion assays in vitro. Cell cycle was measured by flow cytometry assays. Western blotting and qRT-PCR were performed to investigate the potential mechanisms by which SOX18 leads to tumor progression. KEY FINDINGS: SOX18 was significantly upregulated in BCa and its expression was associated with clinical features of patients with BCa. Our data demonstrated that SOX18 promoted cell proliferation via accelerating cell cycle and by regulating c-Myc and Cyclin D1, promoted cell invasion via upregulation of MMP-7. Moreover, phosphorylation of c-Met and Akt regulated by SOX18 was identified to be involved in the process of cell migration and invasion, indicating the vital role of SOX18 in the metastasis of BCa. SIGNIFICANCE: Our data demonstrated a cancer-promoting effect of SOX18 in BCa, revealed the potential mechanisms of SOX18 in mediating cellular functions, and indicated that SOX18 may serve as a promising progression and prognostic biomarker and a therapeutic target for BCa.


Assuntos
Fatores de Transcrição SOXF/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Ciclina D1/metabolismo , Feminino , Fase G1/fisiologia , Xenoenxertos , Humanos , Masculino , Metaloproteinase 7 da Matriz/metabolismo , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fase S/fisiologia , Fatores de Transcrição SOXF/biossíntese , Fatores de Transcrição SOXF/genética , Transcriptoma/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
12.
Nat Commun ; 10(1): 2913, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266935

RESUMO

Mechanistic studies in human cancer have relied heavily on cell lines and mouse models, but are limited by in vitro adaptation and species context issues, respectively. More recent efforts have utilized patient-derived xenografts; however, these are hampered by variable genetic background, inability to study early events, and practical issues with availability/reproducibility. We report here an efficient, reproducible model of T-cell leukemia in which lentiviral transduction of normal human cord blood yields aggressive leukemia that appears indistinguishable from natural disease. We utilize this synthetic model to uncover a role for oncogene-induced HOXB activation which is operative in leukemia cells-of-origin and persists in established tumors where it defines a novel subset of patients distinct from other known genetic subtypes and with poor clinical outcome. We show further that anterior HOXB genes are specifically activated in human T-ALL by an epigenetic mechanism and confer growth advantage in both pre-leukemia cells and established clones.


Assuntos
Proteínas de Homeodomínio/metabolismo , Leucemia/metabolismo , Família Multigênica , Animais , Proliferação de Células , Epigênese Genética , Feminino , Xenoenxertos , Proteínas de Homeodomínio/genética , Humanos , Leucemia/genética , Leucemia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Modelos Genéticos , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo
13.
Anal Chim Acta ; 1074: 69-79, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159941

RESUMO

The characterization of cancer tissues by matrix-assisted laser desorption ionization-mass spectrometry images (MALDI-MSI) is of great interest because of the power of MALDI-MS to understand the composition of biological samples and the imaging side that allows for setting spatial boundaries among tissues of different nature based on their compositional differences. In tissue-based cancer research, information on the spatial location of necrotic/tumoral cell populations can be approximately known from grayscale images of the scanned tissue slices. This study proposes as a major novelty the introduction of this physiologically-based information to help in the performance of unmixing methods, oriented to extract the MS signatures and distribution maps of the different tissues present in biological samples. Specifically, the information gathered from grayscale images will be used as a local rank constraint in Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) for the analysis of MALDI-MSI of cancer tissues. The use of this constraint, setting absence of certain kind of tissues only in clear zones of the image, will help to improve the performance of MCR-ALS and to provide a more reliable definition of the chemical MS fingerprint and location of the tissues of interest. The general strategy to address the analysis of MALDI-MSI of cancer tissues will involve the study of the MCR-ALS results and the posterior use of MCR-ALS scores as dimensionality reduction for image segmentation based on K-means clustering. The resolution method will provide the MS signatures and their distribution maps for each tissue in the sample. Then, the resolved distribution maps for each biological component (MCR scores) will be submitted as initial information to K-means clustering for image segmentation to obtain information on the boundaries of the different tissular regions in the samples studied. MCR-ALS prior to K-means not only provides the desired dimensionality reduction, but additionally resolved non-biological signal contributions are not used and the weight given to the different biological components in the segmentation process can be modulated by suitable preprocessing methods.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Neoplasias/patologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Algoritmos , Animais , Análise por Conglomerados , Cor , Feminino , Células HCT116 , Xenoenxertos/patologia , Humanos , Análise dos Mínimos Quadrados , Camundongos Nus , Análise Multivariada , Análise de Regressão , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/estatística & dados numéricos
14.
Gynecol Oncol ; 154(3): 495-504, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31204077

RESUMO

OBJECTIVE: This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes. METHODS: We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (n = 21 discovery set; n = 18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (P < .05) with no increased expression in paired benign bowel tissue and were validated with quantitative reverse transcription PCR. Using an independent OC cohort (n = 333), associations between DEGs in PTs and surgical and clinical outcomes were performed. Immunohistochemistry and mouse xenograft studies were performed to confirm the role of LRRC15 in promoting metastasis. RESULTS: Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice. CONCLUSIONS: We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC.


Assuntos
Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Neoplasias Intestinais/genética , Neoplasias Intestinais/secundário , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Animais , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Nus , RNA Neoplásico/genética , Transcriptoma , Regulação para Cima
15.
Pharm Res ; 36(8): 121, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31214786

RESUMO

PURPOSE: ß-elemene and cisplatin combined chemotherapy currently is one of the most important settings available for lung cancer therapy in China. However, the clinical outcome is limited by their pharmacokinetic drawbacks. On the other hand, most of nanomedicines have failed in clinical development due to the huge differences between heterogeneous clinical tumor tissues and homogenous cell-derived xenografts. In this work, we fabricated a ß-elemene and cisplatin co-loaded liposomal system to effectively treat lung cancer. METHOD: In vitro cytotoxicity of co-loaded liposomes was studied by MTT, trypan and Hoechst/PI staining, and western blot in A549, A549/DDP, and LCC cells. In vivo antitumor efficacy was evaluated in cell-derived and clinically relevant patient-derived xenografts. RESULTS: Co-loaded liposomes were more cytotoxic to cancer cells, especially than the combination of single-loaded liposomes, benefiting from their simultaneous drug internalization and release. As a result, they exhibited desirable therapeutic outcome in both cell-derived and patient-derived xenografts. CONCLUSION: ß-elemene and cisplatin co-loaded liposomes are a clinically promising candidate for effective lung cancer therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cisplatino/farmacocinética , Lipossomos/química , Neoplasias Pulmonares/tratamento farmacológico , Sesquiterpenos/farmacocinética , Células A549 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Cisplatino/administração & dosagem , Composição de Medicamentos , Liberação Controlada de Fármacos , Xenoenxertos , Humanos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Sesquiterpenos/administração & dosagem , Distribuição Tecidual
16.
Transplant Proc ; 51(5): 1458-1462, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31155179

RESUMO

BACKGROUND: Subcutaneous pockets provide an extrahepatic transplant site for islet grafting to treat type 1 diabetes. However, a hypoxic environment may cause central necrosis to islets and lead to graft failure. Our previous studies focused on a pre-treated subcutaneous site with basic fibroblast growth factor (bFGF) for the formation of vascular bed. In addition to neovascularization, bFGF was also shown to protect islets against oxidative stress and chemical-induced damage in vitro. Accordingly, we propose that subcutaneous islet transplantation with a bFGF-slow releasing device simultaneously can improve islet survival in vivo. METHODS: A bFGF-impregnated collagen sheet was implanted in the right back of a streptozotocin-induced diabetic mouse for neovascularization. After 10 days, the sheet was removed and the rat islet-embedding gel within the immune-isolation device was transplanted (2-time operation [OP]). In another group, the diabetic mice received bFGF-impregnated gel with rat islets within the immune-isolation device simultaneously (1-time OP). RESULTS: Diabetic mice in 2-time OP group experienced a decrease in their non-fasting blood glucose level for a period of 10 days, and the glucose levels were lower than those of untreated diabetic mice post-implantation. However, the mice in the 1-time OP group remained hyperglycemic post-operation and showed no improvements in body weight or the area under curve in intraperitoneal glucose tolerance test. Furthermore, mice in the 2-time OP had relatively higher serum insulin levels with improved renal and metabolic biomarkers. CONCLUSION: Our findings suggest that bFGF had no beneficial effect on a 1-time operation in subcutaneous islet transplantation.


Assuntos
Diabetes Mellitus Experimental/cirurgia , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Transplante das Ilhotas Pancreáticas/instrumentação , Transplante das Ilhotas Pancreáticas/métodos , Tela Subcutânea , Animais , Glicemia , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Xenoenxertos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Tela Subcutânea/cirurgia
17.
Life Sci ; 231: 116549, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31200002

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) is emerging as an important regulator in various physiological and pathological processes. Recently, it was found that lncRNA long non-coding RNA tumor suppressor candidate 7 (TUSC7) could play tumor suppressive roles in several cancers. However, the function and underlying regulatory mechanism of lncRNA TUSC7 in endometrial carcinoma (EC) remains largely unclear. METHODS: The expression levels of TUSC7 and microRNAs-616 (miR-616) were analyzed by real-time PCR and in situ hybridization. Cell cycle and cell metastasis associated protein expressions were determined by western blotting. Cell proliferation, cycle and metastasis were determined by CCK-8 cell viability, colony formation, flow cytometer, wound scratch and transwell assays respectively in vitro. RNA pull-down, luciferase and western blotting assays were used to examine the target relationship between TUSC7 and miR-616 or that between miR-616 and suppressors of cytokine signaling 4 (5) (SOCS4 (SOCS5)). The functional effects of TUSC7 through sponging miR-616 were further examined using a xenograft tumor mouse model in vivo. RESULTS: TUSC7 was downexpressed in EC tissues and cell lines, and TUSC7 upregulation could remarkably inhibit cell proliferation, cycle progression and metastasis in EC cells. Mechanistic investigations demonstrated that TUSC7 can interact with miR-616 and decrease its expression, thereby upregulating the expression of miR-616's targets SOCS4 (SOCS5). Additionally, in vivo experiments using a xenograft tumor mouse model revealed that TUSC7 can serve as a tumor suppressor through sponging miR-616, and upregulating SOCS4 (SOCS5) in EC. CONCLUSIONS: In this study, a newly identified regulatory mechanism of lncRNA TUSC7/miR-616/ SOCS4 (SOCS5) axis was systematically studied, which may hold promise as a promising target for EC treatment.


Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Animais , Apoptose , Técnicas de Cultura de Células , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias do Endométrio/patologia , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Proteínas Supressoras da Sinalização de Citocina/genética
18.
J Biomed Nanotechnol ; 15(8): 1801-1811, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219008

RESUMO

Iron oxide nanoparticles (IONPs) have shown great potential in various biomedical applications. However, information on the interaction between IONPs and biological systems, especially the uptake and distribution of IONPs in cells and tissues, as well as the mechanism of biological action, is relatively limited. In the present study, multi-modal visualization methods, including confocal fluorescence microscopy, transmission electron microscopy, magnetic resonance imaging, and fluorescence optical imaging, were utilized to unveil the uptake and distribution of IONPs in macrophages, cancer cells, and xenograft models. Our results demonstrated that uptake of IONPs in RAW264.7 macrophages and SKOV-3 cancer cells were dose- and cell type-dependent. Cellular uptake of IONPs was an energy-dependent process, and caveolae-mediated endocytosis was the main uptake pathway. All the IONPs were primarily present in endocytic compartments (e.g., endosomes, lysosomes) inside the cells. At 48 hours after intravenous injection of IONPs in SKOV-3 tumor bearing mice, most of the IONPs was distributed in the liver and spleen, with obvious uptake in the tumor, less but significant amount in the kidney and brain. Taken together, multi-modal visualization approaches in our study provide detailed information on the cellular uptake and tissue distribution of IONPs from multiple levels and perspectives.


Assuntos
Nanopartículas , Animais , Compostos Férricos , Xenoenxertos , Macrófagos , Camundongos
19.
20.
Clin Oral Implants Res ; 30(9): 872-881, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172607

RESUMO

OBJECTIVES: To test whether or not the use of a xenogeneic block loaded with rhBMP-2 results in superior radiological and profilometric outcomes compared to an autogenous bone block. MATERIALS AND METHODS: Twenty-four patients randomly received a xenogeneic block loaded with rhBMP-2 (test) or an autogenous bone block (control) for primary augmentation. The ridge width (RW) was evaluated by means of a CBCT scan after augmentation surgery and at 4 months, prior to implant placement. Surface scans were taken prior to augmentation and at 4 months for profilometric analyses. Data were analyzed with Wilcoxon-signed rank test, Mann-Whitney test, or nonparametric ANOVA models. RESULTS: The median RW after augmentation amounted to 7.13 mm (Q1 = 6.02; Q3 = 8.47) for test and 6.86 mm (Q1 = 5.99; Q3 = 8.95) for control. During 4 months of healing, the total RW decreased statistically significantly and measured 5.35 mm (Q1 = 4.53; Q3 = 6.7) for test and 5.15 mm (Q1 = 3.57; Q3 = 7.24) for control (p = 0.0005). The differences between the groups were not statistically significant (p > 0.5899). The buccal soft tissue contour slightly increased for test (0.83 mm; Q1 = 0.62; Q3 = 1.87) and control (1.16 mm; Q1 = 0.50; Q3 = 1.44). CONCLUSIONS: Both treatment modalities successfully increased the ridge width to a similar extent. The shrinkage during healing was not greater in the test than in the control group. The impact of hard tissue augmentation on the soft tissue contour was, however, minimal.


Assuntos
Aumento do Rebordo Alveolar , Proteína Morfogenética Óssea 2 , Transplante Ósseo , Implantação Dentária Endo-Óssea , Xenoenxertos , Humanos , Transplante Heterólogo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA