Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
Int J Mol Sci ; 25(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38203629

RESUMO

Among the several mechanisms accounting for endocrine resistance in breast cancer, autophagy has emerged as an important player. Previous reports have evidenced that tamoxifen (Tam) induces autophagy and activates transcription factor EB (TFEB), which regulates the expression of genes controlling autophagy and lysosomal biogenesis. However, the mechanisms by which this occurs have not been elucidated as yet. This investigation aims at dissecting how TFEB is activated and contributes to Tam resistance in luminal A breast cancer cells. TFEB was overexpressed and prominently nuclear in Tam-resistant MCF7 cells (MCF7-TamR) compared with their parental counterpart, and this was not dependent on alterations of its nucleo-cytoplasmic shuttling. Tam promoted the release of lysosomal Ca2+ through the major transient receptor potential cation channel mucolipin subfamily member 1 (TRPML1) and two-pore channels (TPCs), which caused the nuclear translocation and activation of TFEB. Consistently, inhibiting lysosomal calcium release restored the susceptibility of MCF7-TamR cells to Tam. Our findings demonstrate that Tam drives the nuclear relocation and transcriptional activation of TFEB by triggering the release of Ca2+ from the acidic compartment, and they suggest that lysosomal Ca2+ channels may represent new druggable targets to counteract the onset of autophagy-mediated endocrine resistance in luminal A breast cancer cells.


Assuntos
Cálcio , Neoplasias , Tamoxifeno/farmacologia , Cálcio da Dieta , Autofagia , Lisossomos
2.
Antioxidants (Basel) ; 10(12)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34943045

RESUMO

Melanoma is a highly aggressive cancer with the poorest prognosis, representing the deadliest form of skin cancer. Activating mutations in BRAF are the most frequent genetic alterations, present in approximately 50% of all melanoma cases. The use of specific inhibitors towards mutant BRAF variants and MEK, a downstream signaling target of BRAF in the MAPK pathway, has significantly improved progression-free and overall survival in advanced melanoma patients carrying BRAF mutations. Nevertheless, despite these improvements, resistance still develops within the first year of therapy in around 50% of patients, which is a significant problem in managing BRAF-mutated advanced melanoma. Understanding these mechanisms is one of the mainstreams of the research on BRAFi/MEKi acquired resistance. Both genetic and epigenetic mechanisms have been described. Moreover, in recent years, oxidative stress has emerged as another major force involved in all the phases of melanoma development, from initiation to progression until the onsets of the metastatic phenotype and chemoresistance, and has thus become a target for therapy. In the present review, we discuss the current knowledge on oxidative stress and its signaling in melanoma, as well as the oxidative stress-related mechanisms in the acquired resistance to targeted therapies.

3.
Antioxidants (Basel) ; 10(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34829605

RESUMO

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily. Originally described as "orphan nuclear receptors", they can bind both natural and synthetic ligands acting as agonists or antagonists. In humans three subtypes, PPARα, ß/δ, γ, are encoded by different genes, show tissue-specific expression patterns, and contribute to the regulation of lipid and carbohydrate metabolisms, of different cell functions, including proliferation, death, differentiation, and of processes, as inflammation, angiogenesis, immune response. The PPAR ability in increasing the expression of various antioxidant genes and decreasing the synthesis of pro-inflammatory mediators, makes them be considered among the most important regulators of the cellular response to oxidative stress conditions. Based on the multiplicity of physiological effects, PPAR involvement in cancer development and progression has attracted great scientific interest with the aim to describe changes occurring in their expression in cancer cells, and to investigate the correlation with some characteristics of cancer phenotype, including increased proliferation, decreased susceptibility to apoptosis, malignancy degree and onset of resistance to anticancer drugs. This review focuses on mechanisms underlying the antioxidant and anti-inflammatory properties of PPARs in physiological conditions, and on the reported beneficial effects of PPAR activation in cancer.

4.
Antioxidants (Basel) ; 10(4)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805928

RESUMO

Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

5.
Cancers (Basel) ; 13(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809171

RESUMO

Endocrine resistance is a major complication during treatment of estrogen receptor-positive breast cancer. Although autophagy has recently gained increasing consideration among the causative factors, the link between autophagy and endocrine resistance remains elusive. Here, we investigate the autophagy-based mechanisms of tamoxifen resistance in MCF7 cells. Tamoxifen (Tam) triggers autophagy and affects the lysosomal compartment of MCF7 cells, such that activated autophagy supports disposal of tamoxifen-damaged lysosomes by lysophagy. MCF7 cells resistant to 5 µM tamoxifen (MCF7-TamR) have a higher autophagic flux and an enhanced resistance to Tam-induced lysosomal alterations compared to parental cells, which suggests a correlation between the two events. MCF7-TamR cells overexpress messenger RNAs (mRNAs) for metallothionein 2A and ferritin heavy chain, and they are re-sensitized to Tam by inhibition of autophagy. Overexpressing these proteins in parental MCF7 cells protects lysosomes from Tam-induced damage and preserves viability, while inhibiting autophagy abrogates lysosome protection. Consistently, we also demonstrate that other breast cancer cells that overexpress selected mRNAs encoding iron-binding proteins are less sensitive to Tam-induced lysosomal damage when autophagy is activated. Collectively, our data demonstrate that autophagy triggers Tam resistance in breast cancer cells by favoring the lysosomal relocation of overexpressed factors that restrain tamoxifen-induced lysosomal damage.

6.
Front Bioeng Biotechnol ; 8: 589223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33553112

RESUMO

Abdominal hernia repair is a frequently performed surgical procedure worldwide. Currently, the use of polypropylene (PP) surgical meshes for the repair of abdominal hernias constitutes the primary surgical approach, being widely accepted as superior to primary suture repair. Surgical meshes act as a reinforcement for the weakened or damaged tissues and support tissue restoration. However, implanted meshes could suffer from poor integration with the surrounding tissues. In this context, the present study describes the preliminary evaluation of a PCL-Gel-based nanofibrous coating as an element to develop a multicomponent hernia mesh device (meshPCL-Gel) that could overcome this limitation thanks to the presence of a nanostructured biomimetic substrate for enhanced cell attachment and new tissue formation. Through the electrospinning technique, a commercial PP hernia mesh was coated with a nanofibrous membrane from a polycaprolactone (PCL) and gelatin (Gel) blend (PCL-Gel). Resulting PCL-Gel nanofibers were homogeneous and defect-free, with an average diameter of 0.15 ± 0.04 µm. The presence of Gel decreased PCL hydrophobicity, so that membranes average water contact angle dropped from 138.9 ± 1.1° (PCL) to 99.9 ± 21.6°, while it slightly influenced mechanical properties, which remained comparable to those of PCL (E = 15.7 ± 2.7 MPa, σ R = 7.7 ± 0.6 ε R = 118.8 ± 13.2%). Hydrolytic and enzymatic degradation was conducted on PCL-Gel up to 28 days, with maximum weight losses around 20 and 40%, respectively. The meshPCL-Gel device was obtained with few simple steps, with no influences on the original mechanical properties of the bare mesh, and good stability under physiological conditions. The biocompatibility of meshPCL-Gel was assessed by culturing BJ human fibroblasts on the device, up to 7 days. After 24 h, cells adhered to the nanofibrous substrate, and after 72 h their metabolic activity was about 70% with respect to control cells. The absence of detectable lactate dehydrogenase in the culture medium indicated that no necrosis induction occurred. Hence, the developed nanostructured coating provided the meshPCL-Gel device with chemical and topographical cues similar to the native extracellular matrix ones, that could be exploited for enhancing the biological response and, consequently, mesh integration, in abdominal wall hernia repair.

7.
Chem Biol Interact ; 292: 9-14, 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-29986832

RESUMO

Breast cancer chemotherapy can cause side effects due to nonspecific drug delivery, low solubility and fast metabolism of drugs used in conventional therapy. Moreover, the therapeutic effect of the drugs is often reduced by the strengthening of chemoresistance, which occurs via a variety of mechanisms. Different strategies have been developed to reduce multidrug resistance (MDR)-associated gene expressions including the use of surfactants and polymers. In this study superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with conjugated linoleic acid (CLA) reduced the number and viability of cells in comparison with both untreated cells or cells treated with SPIONs alone. This cytostatic effect correlated with the increase of peroxisome proliferator-activated receptors γ (PPARγ). The necrotic cell death induced, as a consequence, an inflammatory process, as evidenced by the decrease of the anti-inflammatory PPARα and increase of pro-inflammatory TNFα and IL-1ß. PPARs were examined because CLA is one of their natural ligands. The antitumor effect observed was accompanied by a down-regulation of p-glycoprotein (P-gp), which was the first important discovered efflux transporter belonging to MDR, and of ALDH3A1, an enzyme able to metabolize some drugs, reducing their effects. The down-regulation of P-gp correlated with the increase of cytokines. The ALDH3A1 decrease correlated with the increase of PPARγ. Based on these results, PPARs are molecular mediators of anti-cancer effect of SPIONs functionalized with CLA, being changes in these nuclear receptors correlated with induction of cytotoxicity and inflammation, and decreased ability of cancer cells in blocking anti-cancer drug effect.


Assuntos
Antineoplásicos/farmacologia , Ácidos Linoleicos Conjugados/química , Nanopartículas de Magnetita/química , Receptores Ativados por Proliferador de Peroxissomo/farmacologia , Anilidas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Feminino , Interleucina-1beta/metabolismo , Ácidos Linoleicos Conjugados/uso terapêutico , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Fator de Necrose Tumoral alfa/metabolismo
9.
Mater Sci Eng C Mater Biol Appl ; 76: 439-447, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28482548

RESUMO

One of the goals for the development of more effective cancer therapies with reduced toxic side effects is the optimization of innovative treatments to selectively kill tumor cells. The use of nanovectors loaded with targeted therapeutic payloads is one of the most investigated strategies. In this paper superparamagnetic iron oxide nanoparticles (SPIONs) coated by a silica shell or uncoated, were functionalized with single-layer and bi-layer conjugated linoleic acid (CLA). Silica was used to protect the magnetic core from oxidation, improve the stability of SPIONs and tailor their surface reactivity. CLA was used as novel grafting biomolecule for its anti-tumor activity and to improve particle dispersibility. Mouse breast cancer 4T1 cells were treated with these different SPIONs. SPIONs functionalized with the highest quantity of CLA and coated with silica shell were the most dispersed. Cell viability was reduced by SPIONs functionalized with CLA in comparison with cells which were untreated or treated with SPIONs without CLA. As regards the types of SPIONs functionalized with CLA, the lowest viability was observed in cells treated with uncoated SPIONs with the highest quantity of CLA. In conclusion, the silica shell free SPIONs functionalized with the highest amount of CLA can be suggested as therapeutic carriers because they have the best dispersion and ability to decrease 4T1 cell viability.


Assuntos
Nanopartículas de Magnetita , Animais , Sobrevivência Celular , Humanos , Ferro , Ácido Linoleico , Camundongos , Neoplasias , Dióxido de Silício
10.
J Biomed Mater Res B Appl Biomater ; 105(6): 1586-1593, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27126254

RESUMO

Hernias are generally repaired using synthetic prostheses. Infection may already be present or develop during implantation. Based on the increasing resistance to antibiotics, and the well-known antimicrobial properties of silver (Ag), the possibility of coating hernia prostheses with a nanostructured layer containing Ag was explored. Prostheses (Clear Mesh Composite [CMC]) made up of two polypropylene layers (macroporous light mesh and thin transparent film) were tested with human mesothelial cells from omentum biopsies. Mesotheliocytes modulate abdominal wall healing producing cytokines, growth factors, and adhesion molecules. Evaluating the growth of these cells on CMC or film alone showed that cell numbers on CMC increased over time, and were higher than those on film alone. Vimentin immunostaining confirmed the cells to be mesotheliocytes. Subsequently, the biocompatibility of mesh layer, coated or not with a thin layer of Ag/SiO2 -nanoclusters, was analyzed, showing no difference in absence or presence of Ag/SiO2 . Differently, TGF-ß2 production, involved in tissue repair and fibrosis, increased in the presence of Ag/SiO2 . Moreover, Ag/SiO2 -coated mesh showed antibacterial properties. In conclusion, the mesh layer coated with Ag/SiO2 afforded cell growth, and showed antibacterial activity. Coating only the mesh layer did not decrease film transparency, and did not favor the formation of adhesions on the visceral side. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1586-1593, 2017.


Assuntos
Materiais Revestidos Biocompatíveis , Hérnia , Herniorrafia , Implantes Experimentais , Teste de Materiais , Peritônio/metabolismo , Polipropilenos , Dióxido de Silício , Prata , Telas Cirúrgicas , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Epitélio/metabolismo , Feminino , Humanos , Masculino , Peritônio/citologia , Polipropilenos/química , Polipropilenos/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Prata/química , Prata/farmacologia
11.
Antioxidants (Basel) ; 5(1)2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26907355

RESUMO

In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations.

12.
Lipids ; 48(1): 29-38, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23129255

RESUMO

Conjugated linoleic acid (CLA) is thought to have anti-proliferative and anti-inflammatory properties, but its effect on cancer cachexia is unknown. Two effects were here investigated: that of CLA on inflammatory mediator production in human lung cancer cells, and that of reduced mediators on the myogenic differentiation of murine muscle C2C12 cells. The latter cells were grown in medium conditioned by human lung cancer A427 cells, with or without CLA, to mimic only the effect of molecules released from the tumor "in vivo", excluding the effect of host-produced cachectic factors. The results obtained show that CLA was found to reduce the production of tumor necrosis factor-α, interleukin (IL)-1ß and prostaglandin E2 (PGE2), but had no effect on IL-6 production. The mechanisms underlying the effect of CLA on cytokine or PGE2 release in A427 cells are probably mediated by activation of peroxisome proliferator-activated receptor (PPAR)α, which increased at 24 h CLA treatment. In turn, the reduced content of inflammatory mediators in medium conditioned by A427 cells, in the presence of CLA, allowed muscle cells to proliferate, again by inducing PPAR. The involvement of PPARα was demonstrated by treatment with the antagonist MK-886. The findings demonstrate the anti-inflammatory and myogenic action of CLA and point to its possible application as a novel dietary supplement and therapeutic agent in inflammatory disease states, such as cachexia.


Assuntos
Anticarcinógenos/farmacologia , Mediadores da Inflamação/imunologia , Ácidos Linoleicos Conjugados/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Células Musculares/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Dinoprostona/imunologia , Cavalos , Indóis/farmacologia , Interleucina-1/imunologia , Interleucina-6/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos , Células Musculares/citologia , Receptores Ativados por Proliferador de Peroxissomo/imunologia
13.
Clin Oral Investig ; 17(4): 1259-66, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22864527

RESUMO

OBJECTIVES: The intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget's disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa "in vivo." PATIENTS AND METHODS: Specimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF). RESULTS: Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased. CONCLUSIONS: Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio. CLINICAL RELEVANCE: The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Células Endoteliais/fisiologia , Imidazóis/efeitos adversos , Mucosa Bucal/metabolismo , Osteoclastos/fisiologia , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Estudos de Casos e Controles , Proliferação de Células , Citocinas/metabolismo , Difosfonatos/administração & dosagem , Feminino , Líquido do Sulco Gengival/química , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Imidazóis/administração & dosagem , Injeções Intravenosas/efeitos adversos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mieloma Múltiplo/tratamento farmacológico , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Estatísticas não Paramétricas , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ácido Zoledrônico
14.
Br J Nutr ; 108(2): 327-33, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22114792

RESUMO

PUFA from fish oil appear to have anti-inflammatory and anti-oxidative effects and improve nutritional status in cancer patients. With this as background, the aim of the present study was to investigate the effect of EPA plus DHA on inflammatory condition, and oxidative and nutritional status in patients with lung cancer. In our multicentre, randomised, double-blind trial, thirty-three patients with a diagnosis of advanced inoperable non-small-cell lung cancer and undergoing chemotherapy were divided into two groups, receiving four capsules/d containing 510 mg of EPA and 340 mg of DHA, or 850 mg of placebo, for 66 d. At the start of chemotherapy (T0), after 8 d (T1), 22 d (T2) and 66 d (T3), biochemical (inflammatory and oxidative status parameters) and anthropometric parameters were measured in both groups. A significant increase of body weight in the n-3 group at T3 v. T0 was observed. Concerning inflammation, C-reactive protein and IL-6 levels differed significantly between the n-3 and placebo groups at T3, and progressively decreased during chemotherapy in the n-3 group, evidencing n-3 PUFA anti-inflammatory action. Concerning oxidative status, plasma reactive oxygen species levels increased in the placebo group v. the n-3 group at the later treatment times. Hydroxynonenal levels increased in the placebo group during the study, while they stabilised in the n-3 group. Our data confirm that the continual assumption of EPA plus DHA determined an anti-inflammatory and anti-oxidative action which could be considered a preliminary goal in anti-cachectic therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/dietoterapia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Neoplasias Pulmonares/dietoterapia , Anti-Inflamatórios não Esteroides/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antioxidantes/efeitos adversos , Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Terapia Combinada/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Humanos , Interleucina-6/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Masculino , Estresse Oxidativo , Pacientes Desistentes do Tratamento , Aumento de Peso , Gencitabina
15.
Lasers Med Sci ; 27(2): 353-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21279404

RESUMO

Alveolar healing following tooth extraction is a complex repair process involving different tissues, including epithelium and bone. This research aimed to study the effect of laser therapy on alveolar healing process in patients waiting for liver transplantation, evaluating some inflammation, osteogenesis, and clinical parameters. Twelve patients with hepatic failure waiting for liver transplantation, with indications to bilateral extraction, entered the split-mouth study. One post-extractive defect was treated with laser while the other was left without treatment. Specimens of soft tissues were removed from around the tooth before extraction and after 7 days. Superpulsed laser irradiation prevented IL-1ß increase and induced IL-6, IL-10, and collagen III increase at 7 days in comparison to their level before extraction, whereas the other parameters were unmodified. Moreover, the epithelial regeneration evidenced a positive result of laser therapy, and the patients reported less pain in the site treated with laser. In conclusion, laser therapy appears to be the treatment of choice for patients due to its clinical efficacy, safety, good tolerance, and its ability to prevent inflammation.


Assuntos
Processo Alveolar/efeitos da radiação , Terapia a Laser , Falência Hepática/complicações , Osteogênese/efeitos da radiação , Extração Dentária , Cicatrização/efeitos da radiação , Citocinas/metabolismo , Colágenos Fibrilares/metabolismo , Humanos , Falência Hepática/fisiopatologia , Transplante de Fígado , Reação em Cadeia da Polimerase em Tempo Real , Cicatrização/fisiologia
16.
Photomed Laser Surg ; 29(8): 565-71, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21631375

RESUMO

OBJECTIVE: This research studied the effects of laser therapy on healing processes following tooth extraction in healthy human subjects, evaluating some inflammation, osteogenesis, and clinical parameters. BACKGROUND DATA: Alveolar healing following tooth extraction is a complex repair process involving different types of tissues, including epithelium and bone. Therefore, it can be advantageous to use techniques able to influence the healing of all tissues. PATIENTS AND METHODS: Ten healthy human subjects with indications for bilateral tooth extraction entered the split-mouth study. The subject/patient becomes his/her own control, thereby eliminating all individual differences in response to laser treatment. This consisted of: 904-nm laser, 33 W peak power, 30 KHz, 200 ns, average power 200 mW, illuminated area 1 cm(2), 200 mW/cm(2), 15 min, 180 J, 180 J/cm(2). In each patient, one post-extraction site was treated with laser radiation, whereas the other was left untreated as a control. Soft-tissue specimens were removed from the extraction site before tooth extraction (T0) and 7 days after from extraction (T7); expression of inflammatory and osteogenesis parameters was evaluated on these specimens. The clinical parameter "pain" was evaluated for each subject. RESULTS: Superpulsed laser irradiation prevented the increase of interleukin (IL)-1ß, IL-6, IL-10, and cyclooxygenase-2 (COX-2), and induced an insignificant increase in collagen at 7 days after extraction, versus levels on day of extraction; no changes were found in the other parameters examined. Patients reported less pain at the site treated with superpulsed laser irradiation than at the control site. CONCLUSIONS: This study suggests that superpulsed laser irradiation may be a treatment of choice for patients scheduled for tooth extraction, as it provides clinical efficacy, is safe and well tolerated, and is able to prevent inflammation.


Assuntos
Terapia com Luz de Baixa Intensidade , Extração Dentária , Cicatrização/efeitos da radiação , Adolescente , Adulto , Análise de Variância , Colágeno/efeitos da radiação , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas , Resultado do Tratamento
17.
JPEN J Parenter Enteral Nutr ; 35(1): 114-21, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21224438

RESUMO

BACKGROUND: ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)-induced cytokine release by human alveolar cells was affected by changes in the ω-3/ω-6 ratio of cell membranes induced by different supplies of PUFAs. METHODS: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured. RESULTS: The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω-6 over ω-3 in the ω-3/ω-6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin-6, and interleukin-8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti-inflammatory interleukin-10 (P < .001). The balance between proinflammatory and anti-inflammatory cytokines showed an anti-inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001). CONCLUSIONS: This study showed that proinflammatory cytokine release was dependent on the proportion of ω-3 in the ω-3/ω-6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω-6 to ω-3 in nutrition support of patients with acute lung injury.


Assuntos
Citocinas/biossíntese , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Análise de Variância , Linhagem Celular , Membrana Celular/metabolismo , Células Epiteliais/metabolismo , Humanos , Inflamação/prevenção & controle , Interleucina-10/análise , Interleucina-6/análise , Interleucina-8/análise , Lipopolissacarídeos/farmacologia , Modelos Teóricos , Alvéolos Pulmonares/citologia , Fator de Necrose Tumoral alfa/análise
18.
Cell Biochem Funct ; 28(7): 571-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20862655

RESUMO

Peroxisome proliferator-activated receptors (PPARs) mediate the effects of various ligands, known as peroxisome proliferators, a heterogeneous class of compounds including industrial chemicals, pharmaceuticals, and biomolecules such as fatty acids and eicosanoids. Among peroxisome proliferators, fibrate derivatives are considered specific ligands for PPARα, whereas eicosanoids, such as PGJ2, for PPARγ. The study aimed to clarify the relation between PPARs and apoptosis or proliferation on the same type of cells, using clofibrate as specific ligand of PPARα and PGJ2 as specific ligand of PPARγ. The cells used were human hepatocarcinoma HepG2 cells. The results showed that PPARα protein content increased in HepG2 cells treated with clofibrate, causing apoptosis in a time- and concentration-dependent way, as evidenced by the citofluorimetric assay and determination of BAD, myc and protein phosphatase 2A protein content. It also emerged that PPARγ increased in the same cells when treated with a specific ligand of this PPAR; in this case the increase of PPARγ did not cause an increase of apoptosis, but a time- and concentration-dependent inhibition of cell proliferation, evidenced by decreased cell numbers and increased number of cells in the G0/G1 phase of the cycle. It may be concluded that PPARα is chiefly related to apoptosis and PPARγ to cell proliferation.


Assuntos
Apoptose , Proliferação de Células , PPAR alfa/metabolismo , PPAR gama/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Clofibrato/farmacologia , Células Hep G2 , Humanos , Ligantes , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Concentração Osmolar , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Proteína de Morte Celular Associada a bcl/metabolismo
19.
J Biomed Mater Res A ; 95(3): 741-6, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20725982

RESUMO

Extraction of an impacted mandibular third molar is a common surgical procedure, although it still leads to several postoperative symptoms and complications. The study assessed the efficacy of autologous plasma rich in growth factors (PRGF) in the healing process by checking the difference of tissue cytokines and other healing factors produced by the mucosa after extraction between sites treated with PRGF and control sites and, at the same time, by evaluating the clinical efficacy of PRGF in terms of reduced pain and facial swelling. This study was a split-mouth study, in which the patient becomes his/her own control, to eliminate any individual response differences toward PRGF treatment. The parameters regarding inflammation and subsequent wound healing were all significantly higher at PRGF sites than at control sites. The increase at PRGF sites of the two proinflammatory cytokines evaluated, interleukin (IL)-1ß and IL-6, was accompanied by the increase of two anti-inflammatory cytokines, IL-10 and transforming growth factor-ß. Furthermore, IL-1ß and IL-6 induce fibroblast and keratinocyte proliferation, important events in wound healing. Postoperative pain and the swelling, measured at all experimental times, were reduced in the presence of PRGF.


Assuntos
Fatores Biológicos , Peptídeos e Proteínas de Sinalização Intercelular , Dente Serotino/cirurgia , Plasma/química , Extração Dentária , Cicatrização/efeitos dos fármacos , Adolescente , Adulto , Animais , Fatores Biológicos/sangue , Fatores Biológicos/farmacologia , Humanos , Inflamação/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Interleucina-10/imunologia , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Dor Pós-Operatória , Distribuição Aleatória , Fator de Crescimento Transformador beta/imunologia , Adulto Jovem
20.
Cancer Lett ; 287(1): 62-6, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19540663

RESUMO

Conjugated linoleic acid (CLA) is reported to have anti-cancer activity, based on animal and in vitro studies. Since it has been suggested that CLA anti-carcinogenic effect stems from its anti-inflammatory properties, this study investigated whether CLA can prevent cell proliferation induced by TPA in human keratinocytes NCTC 2544 contemporary to inhibition of inflammation. Results obtained showed that CLA prevents increased cell proliferation and production of pro-inflammatory molecules determined by TPA, being this effect due to modulation of PPARs and NFkB activity. The involvement of PPARalpha in CLA effect was demonstrated by adding to the cells an antagonist of PPARalpha.


Assuntos
Citocinas/biossíntese , Queratinócitos/efeitos dos fármacos , Ácidos Linoleicos Conjugados/farmacologia , Acetato de Tetradecanoilforbol/toxicidade , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , DNA/metabolismo , Humanos , NF-kappa B/metabolismo , PPAR alfa/antagonistas & inibidores , PPAR alfa/fisiologia , PPAR beta/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA