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1.
An Acad Bras Cienc ; 94(suppl 3): e20211394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36197363

RESUMO

The characteristics of milk are controlled by several genes, with emphasis on the four genes from casein, CSN1S1; CSN1S2; CSN2 and CSN3, which are responsible encoding of fractions the milk protein. The study of genetic variants in these genes, seek to investigate alleles, insertions or deletions, that can directly reflect on productive characteristics, indicating differences in milk quality, composition and yield. The CSN1S1 and CSN3 genes were analyzed in lactating Murrah buffaloes using nucleotide sequencing. An SNP was found in the amplified fragment of the CSN1S1 gene, located in nucleotide number 2,123 of the promoter region in position nt-258 (A/G). As for the CSN3 gene, two SNPs of exon number 4 were identified in codons 33 (ACC/ATC) and 34 (ACC/ACT) of the analyzed fragment. This study contributes to important associations between genetic variants and the desired characteristics of milk and its derivatives in future studies, because the variants found may be associated with the quality of milk, enabling genetic selection to be assisted by molecular markers, indicating a major advance that makes it possible to select animals early.


Assuntos
Búfalos , Caseínas , Animais , Brasil , Búfalos/genética , Caseínas/genética , Feminino , Lactação , Proteínas do Leite/genética , Nucleotídeos
2.
J Food Sci Technol ; 57(3): 821-831, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32123402

RESUMO

Oils are subject to several reactions that lead to physical-chemical, sensory and nutritional deterioration. This deterioration process is called rancidity or lipid oxidation, a spontaneous and irreversible phenomenon that can be delayed by the addition of antioxidants. Usually, vegetable oil producers choose to add antioxidants to the upper limit permitted by applicable law as it is not entirely clear the ideal dosages of pure or combined antioxidants designated for this purpose. In order to determine the optimum dosage of antioxidants that minimizes the impact of lipid oxidation of soybean oil bottled in PET (ethylene terephthalate) and replace the traditional antioxidant tert-Butylhydroquinone (TBHQ), an accelerated oven shelf-life test was performed. The antioxidants ascorbyl palmitate (AP), mix of tocopherols and rosemary extract (RE) were evaluated, pure and in combination, at different dosages. Most of the evaluated antioxidants delayed lipid oxidation of soybean oil, but a mixture containing AP and RE presented results of TOTOX statistically lower (higher oxidative stability) than that with TBHQ. One the other hand, regarding OSI at 120 °C, the result obtained by that mixture was statistically lower (less oxidative stability) than that obtained with TBHQ, in both evaluated dosages.

3.
J Chem Phys ; 146(10): 104704, 2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28298127

RESUMO

Free standing graphene is chemically inert but, as recently demonstrated, CO chemisorption occurs at low crystal temperature on the single layer grown by ethene dehydrogenation on Ni(111). Such layer is inhomogeneous since different phases coexist, the relative abundance of which depends on the growth conditions. Here we show by X ray photoemission and high resolution electron energy loss spectroscopies that the attained CO coverage depends strongly on the relative weight of the different phases as well as on the concentration of carbon in the Ni subsurface region. Our data show that the chemical reactivity is hampered by the carbon content in the substrate. The correlation between the amount of adsorbed CO and the weight of the different graphene phases indicates that the top-fcc configuration is the most reactive.

4.
Phys Chem Chem Phys ; 18(28): 18692-6, 2016 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-27373713

RESUMO

We investigate CO adsorption at single vacancies of graphene supported on Ni(111) and polycrystalline Cu. The borders of the vacancies are chemically inert but, on the reactive Ni(111) substrate, CO intercalation occurs. Adsorbed CO dissociates at 380 K, leading to carbide formation and mending of the vacancies, thus preventing their effectiveness in sensor applications.

5.
Phys Rev Lett ; 113(18): 186804, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25396388

RESUMO

Understanding acoustic surface plasmons (ASPs) in the presence of nanosized gratings is necessary for the development of future devices that couple light with ASPs. We show here by experiment and theory that two ASPs exist on Au(788), a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate across the steps as long as their wavelength exceeds the terrace width, thereafter becoming localized. Our investigation identifies, for the first time, ASPs coupled with intersubband transitions involving multiple surface-state subbands.

7.
Langmuir ; 29(23): 6867-75, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23668399

RESUMO

We report here on a combined photoemission and vibrational spectroscopy investigation of (S)-glutamic acid adsorption on Ag(111). We show that, in the temperature range 250 K ≤ T ≤ 400 K, non-zwitterionic adsorption takes place and the anionic form prevails at nonvanishing coverage. Significant conformational changes of the self-assembled layer must occur above 300 K, corresponding to a substantial reduction of the sticking probability and a modification of the vibrational spectrum. The similarity of behavior with respect to glutamic acid adsorption on the previously investigated Ag(100) and Ag(110) surfaces is also discussed.


Assuntos
Ácido Glutâmico/química , Prata/química , Adsorção , Ânions/química , Espectrofotometria , Propriedades de Superfície , Raios X
8.
Knee Surg Sports Traumatol Arthrosc ; 20(7): 1357-65, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22143425

RESUMO

PURPOSE: Biological augmentation to heal a torn anterior cruciate ligament (ACL) has gained significant interest. This study examined the potential advantages of using extracellular matrix (ECM) bioscaffolds from galactosyl-α(1,3)galactose deficient pigs to heal the transected ACL. METHODS: In 16 skeletally mature goats, the ACL in the right hindlimb was transected and repaired. In 9 of these animals, an ECM sheet was wrapped around the injury site and with an ECM hydrogel injected into the transected site. The remaining 7 animals were treated with suture repair only. The left hindlimb served as a sham-operated control. RESULTS: After 12 weeks, the healing ACL in the ECM-treated group showed an abundance of continuous neo-tissue formation, while only limited tissue growth was found after suture repair only. The cross-sectional area of the ACL from the ECM-treated group was similar to sham-operated controls (n.s.) and was 4.5 times those of the suture repair group (P < 0.05). The stiffness of the femur-ACL-tibia complexes from the ECM-treated group was 2.4 times those of the suture repair group (P < 0.05). Furthermore, these values reached 48% of the sham-operated controls (53 ± 19 N/mm and 112 ± 21 N/mm, respectively, P < 0.05). CONCLUSIONS: The application of an ECM bioscaffold and hydrogel was found to accelerate the healing of a transected ACL following suture repair in the goat model with limited tissue hypertrophy and improvement in some of its biomechanical properties. Although more work is necessary to fully restore the function of the normal ACL, these early results offer a potential new approach to aid ACL healing.


Assuntos
Lesões do Ligamento Cruzado Anterior , Matriz Extracelular , Regeneração Tecidual Guiada , Próteses e Implantes , Alicerces Teciduais , Animais , Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Fenômenos Biomecânicos , Galactosiltransferases/deficiência , Cabras , Hidrogel de Polietilenoglicol-Dimetacrilato , Teste de Materiais , Modelos Animais , Suínos , Engenharia Tecidual
9.
Clin Anat ; 25(4): 478-82, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22488997

RESUMO

The transverse carpal ligament is the volar roof of the carpal tunnel. Gross observation shows that the ligament appears to have fibers that roughly orient in the transverse direction. A closer anatomical examination shows that the ligament also has oblique fibers. Knowledge of the fiber orientation of the transverse carpal ligament is valuable for further understanding the ligament's role in regulating the structural function of the carpal tunnel. The purpose of this study is to quantify collagen fiber orientation within the transverse carpal ligament using the small angle light scattering technique. Eight transverse carpal ligament samples from cadaver hands were used in this study. Individual 20-µm sections were cut evenly along the thickness of the transverse carpal ligament. Sections of three thickness levels (25%, 50%, and 75% from the volar surface) were collected for each transverse carpal ligament. Fibers were grouped in the following orientation ranges: transverse, longitudinal, oblique in the pisiform-trapezium (PT), and oblique in the scaphoid-hamate (SH) directions. In analyzing the fiber percentages, the orientation types for the different thickness levels of the ligament showed that the transverse fibers were the most prominent (>60.7%) followed by the PT oblique (18.6%), SH oblique (13.0%), and longitudinal (8.6%) fibers.


Assuntos
Articulações do Carpo/anatomia & histologia , Colágeno/análise , Ligamentos/anatomia & histologia , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Espalhamento a Baixo Ângulo
10.
Bioconjug Chem ; 22(3): 353-61, 2011 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-21361312

RESUMO

There are many liver diseases that could be treated with delivery of therapeutics such as DNA, proteins, or small molecules. Nanoparticles are often proposed as delivery vectors for such therapeutics; however, achieving nanoparticle accumulations in the therapeutically relevant hepatocytes is challenging. In order to address this issue, we have synthesized polymer coated, fluorescent iron oxide nanoparticles that bind and deliver DNA, as well as produce contrast for magnetic resonance imaging (MRI), fluorescence imaging, and transmission electron microscopy (TEM). The composition of the coating can be varied in a facile manner to increase the quantity of poly(ethylene glycol) (PEG) from 0% to 5%, 10%, or 25%, with the aim of reducing opsonization but maintaining DNA binding. We investigated the effect of the nanoparticle coating on DNA binding, cell uptake, cell transfection, and opsonization in vitro. Furthermore, we exploited MRI, fluorescence imaging, and TEM to investigate the distribution of the different formulations in the liver of mice. While MRI and fluorescence imaging showed that each formulation was heavily taken up in the liver at 24 h, the 10% PEG formulation was taken up by the therapeutically relevant hepatocytes more extensively than either the 0% PEG or the 5% PEG, indicating its potential for delivery of therapeutics to the liver.


Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Fígado/citologia , Fígado/metabolismo , Nanopartículas/química , Animais , Transporte Biológico , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Compostos Férricos/química , Compostos Férricos/metabolismo , Compostos Férricos/farmacocinética , Compostos Férricos/toxicidade , Células HEK293 , Meia-Vida , Humanos , Imageamento por Ressonância Magnética , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas/toxicidade , Polietilenoglicóis/química
11.
Langmuir ; 27(6): 2393-404, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21338127

RESUMO

The fundamental understanding of adsorption and self-organization of biological molecules at surfaces is of greatest importance for a huge variety of possible applications, ranging from molecular electronics to the study of biocompatible materials, hygiene, and biofouling. In spite of that, the characterization of the interactions of organic molecules of biological interest with surfaces is far from being complete. In the present paper we report on a combined microscopic (scanning tunneling microscopy (STM)) and spectroscopic (X-ray photoemission spectroscopy and high-resolution electron energy loss spectroscopy) study of glutamic acid (Glu) adsorption and self-assembly on Ag(100) at different temperature. STM allows one to determine the structures of the Glu layers, for which empirical models are proposed, while photoemission spectra exclude adsorption in the zwitterionic form, which is the most common especially for weakly interacting substrates.


Assuntos
Ácido Glutâmico/química , Prata/química , Adsorção , Estereoisomerismo
12.
J Phys Chem A ; 115(25): 7161-8, 2011 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-21526863

RESUMO

Here, we show that the stoichiometry and, consequently, the chemical activity toward hydroxylation of MgO(100) films grown by reactive deposition on Ag(100) strongly depend on the O(2) partial pressure during film growth. Oxygen-deficient films undergo dramatic relative oxygen uptake either by exposure to a partial pressure of water vapor or by aging in vacuum for a sufficiently long time. Conversely, on stoichiometric monolayer MgO islands, photoemission analysis of the O 1s level and scanning tunneling microscopy images are consistent with the prediction that dissociative adsorption of water occurs only at the borders of the islands.

13.
Knee Surg Sports Traumatol Arthrosc ; 19(4): 653-62, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21153545

RESUMO

PURPOSE: Passive anterior knee laxity has been linked to non-contact ACL injury risk. High deceleration movements have been implicated in the non-contact ACL injury mechanism, and evidence suggests that greater anterior tibial translations (ATT) may occur in healthy knees that are lax compared to a tight knee. The purpose of this study was to determine the relationship between anterior knee laxity scores and ATT during drop landings using biplane fluoroscopy. METHODS: Sixteen healthy adults (10 women; 6 men) performed stiff drop landings (40 cm) while being filmed using a high-speed, biplane fluoroscopy system. Initial, peak and excursions for rotations and translations were calculated and regression analysis used to determine the 6DoF kinematic relationships with KT1000 scores with peak ATT occurring during the landing. RESULTS: KT1000 values were (+) correlated with peak ATT values for group (r = 0.89; P < 0.0001) and both genders (males, r = 0.97; P = 0.0003; females, r = 0.93; P = < 0.0001). Regression analysis yielded a significant linear fit for the group (r (2) = 0.80; Y (ATT-group) = - 0.516 + 1.2 × X (KT1000-group)) and for each gender (females: r(2) = 0.86; Y (ATT-females) = 0.074 + 1.2 × X (KT1000-females) and males: r (2) = 0.94; Y (ATT-males) = - 0.79 + 1.2 × X (KT1000-males)). CONCLUSION: A strong relationship was observed between passive anterior knee laxity measured via KT1000 and peak ATT experienced during dynamic activity in otherwise healthy persons performing a stiff drop-landing motion.


Assuntos
Articulação do Joelho/fisiologia , Amplitude de Movimento Articular/fisiologia , Tíbia/fisiologia , Adulto , Análise de Variância , Lesões do Ligamento Cruzado Anterior , Fenômenos Biomecânicos , Feminino , Fluoroscopia/métodos , Humanos , Instabilidade Articular/fisiopatologia , Traumatismos do Joelho/fisiopatologia , Masculino , Modelos Anatômicos , Movimento , Fotofluorografia/métodos , Valores de Referência , Estudos de Amostragem , Suporte de Carga , Adulto Jovem
14.
J Phys Chem Lett ; 12(40): 9894-9898, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34609889

RESUMO

The current understanding of the dynamics of gas-surface interactions is that all of the energy lost in the collision is transferred to vibrations of the target. Electronic excitations were shown to play a marginal role except for cases in which the impinging particles have energies of several electronvolts. Here we show that this picture does not hold for metal surfaces supporting acoustic surface plasmons. Such loss, dressed with a vibronic structure, is shown to make up a prominent energy transfer route down to the terahertz region for Ne atoms scattering off Cu(111) and is expected to dominate for most metals. This mechanism determines, e.g., the drag force acting on telecommunication satellites, which are typically gold-plated to reduce overheating by sunshine. The electronic excitations can be unambiguously discerned from the vibrational ones under mild hyperthermal impact conditions.

15.
Langmuir ; 26(10): 7208-15, 2010 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-20158258

RESUMO

Self-assembly of organic molecules at metal surfaces is of greatest importance in nanoscience; in fact, it opens new perspectives in the field of molecular electronics and in the study of biocompatible materials. Combining an experimental low-temperature scanning tunneling microscopy investigation with ab initio calculations, we succeeded to describe in detail (S)-glutamic acid adsorption on Ag(100) at T = 350 K. We find that (S)-glutamic acid organizes in a squared structure and, at variance with the majority of cases reported in literature, it adsorbs in the neutral form, 4.6 A above the surface plane. The interaction with the poorly reactive Ag substrate is only due to weak van der Waals forces, while H-bonds between carboxyl groups and the formation of a OCOH-OCOH-OCOH-OCOH cycle at the vertex of the squares are the main responsible for the self-assembly.


Assuntos
Ácido Glutâmico/síntese química , Teoria Quântica , Prata/química , Temperatura , Adsorção , Simulação por Computador , Ácido Glutâmico/química , Microscopia de Tunelamento , Modelos Químicos , Estereoisomerismo , Propriedades de Superfície
16.
Knee Surg Sports Traumatol Arthrosc ; 18(1): 11-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19763539

RESUMO

Harvesting both the semitendinosus and gracilis tendons for anterior cruciate ligament (ACL) reconstruction has a negative impact on muscle strength as well as knee function and stability. With a new "All-inside" technique, using only one hamstrings tendon (semitendinosus or gracilis) is possible because of a reduction in length requirements. The research question of this in vitro study was whether the use of only one hamstrings tendon (semitendinosus or gracilis) could restore knee kinematics and in situ force in the ACL to the level of an intact knee.Ten human cadaveric knees were tested in the following conditions: (1) intact, (2) ACL-deficient, and (3) ACL reconstruction with the "All-inside" technique using the (a) single semitendinosus tendon graft, or (b) single gracilis tendon graft. Using a robotic testing system, external loads, i.e. (1) an anterior tibial load of 134-N and (2) combined rotatory loads of 10-Nm valgus and 5-Nm internal tibial torques, were applied. The multiple degrees of freedom knee kinematics and the in situ forces in the ACL and ACL grafts were determined. In response to a 134-N anterior tibial load, the use of either graft could restore anterior tibial translation to within 1.3 mm of the intact knee. The in situ forces in the two grafts were not significantly different from those of the intact ACL. Under the combined rotatory loads, both grafts could restore knee kinematics as well as the in situ force in the grafts to the level of the intact ACL. The "All-inside" technique using either the semitendinosus or gracilis tendon for ACL reconstruction could satisfactorily restore time-zero knee kinematics and the in situ forces in either graft to those for the intact ACL, supporting clinical findings.


Assuntos
Ligamento Cruzado Anterior/cirurgia , Articulação do Joelho/fisiologia , Músculo Esquelético/cirurgia , Procedimentos Ortopédicos/métodos , Tendões/cirurgia , Adulto , Lesões do Ligamento Cruzado Anterior , Fenômenos Biomecânicos , Cadáver , Humanos , Articulação do Joelho/cirurgia , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Tendões/transplante , Transplante Autólogo
17.
J Orthop Translat ; 20: 25-30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31908930

RESUMO

BACKGROUND/OBJECTIVE: In anterior cruciate ligament â€‹reconstruction, a tendon graft, anchored by interference screws (IFSs), is frequently used as a replacement for the damaged ligament. Generally, IFSs are classified as being either metallic or polymeric. Metallic screws have sharp threads that lacerate the graft, preventing solid fixation. These constructs are difficult to image â€‹and can limit bone--screw integration because of the higher stiffness of the screw. Polymeric materials are often a better match to bone's material properties, but lack the strength needed to hold grafts in place. Magnesium (Mg) is a material of great promise for orthopaedic applications. Mg has mechanical properties similar to bone, ability to be seen on magnetic resonance imagings, and promotes bone healing. However, questions still remain regarding the strength of Mg-based screws. Previous ex vivo â€‹animal experiments found stripping of the screw drive when the full torque was applied to Mg screws during surgery, preventing full insertion and poor graft fixation. The similar design of the Mg screw led to questions regarding the relationship between material properties and design, and the ultimate impact on mechanical behaviour. Thus, the objective of this study was to analyze the stresses in the screw head, a key factor in the stripping mechanism of IFS, then use that information to improve screw design, for this material. METHODS: Using finite element analysis, a comparison study of six drive designs (hexagonal, quadrangle, torx, trigonal, trilobe, and turbine) was performed. This was followed by a parametric analysis to determine appropriate drive depth and drive width. RESULTS: It was observed that with a typical torque (2 â€‹Nm) used for screw insertion during anterior cruciate ligament reconstruction, the maximum von Mises and shear stress values were concentrated in the corners or turns of the drive, which could lead to stripping if the values were greater than the yield stress of Mg (193 â€‹MPa). With a four-time â€‹increase in drive depth to be fully driven and a 30% greater drive width, these maximum stress values were significantly decreased by more than 75%. CONCLUSION: It was concluded that improving the design of a Mg-based screw may increase surgical success rates, by decreasing device failure at insertion. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The results of this work have the potential to improve designs of degradable IFSs, allowing for greater torque to be applied and thus greater screw fixation between host bone and the graft. Such a fixation will allow greater integration, better patient healing, and ultimately improved patient outcomes.

18.
Heliyon ; 6(9): e04932, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32995620

RESUMO

PURPOSE: To evaluate the splenic uptake function after irradiation with high-energy X-rays. MATERIALS AND METHODS: Fourteen male Wistar rats were distributed into three groups. Group 1 (n = 6) - control, non-irradiated; Group 2 (n = 4) - animals that were irradiated and studied 24 h after irradiation; and Group 3 (n = 4) - animals that were irradiated and studied 48 h after irradiation. The animals were irradiated with 8 Gy X-rays in the abdominal region. According with the groups, after 24 or 48 h, 1 ml/kg of a 50% colloidal carbon solution was injected in the left internal jugular vein. After 40 min, the spleens were removed for histological studies. Macrophages containing carbon pigments in their cytoplasms were counted in 16 consecutive microscopic fields, and their means were considered as the uptake pattern of each animal. RESULTS: In the control groups, carbon pigments were captured by macrophages in the red and white pulps, while in the irradiated groups, the uptake in the marginal zone, around the white pulp, was enhanced. There was no disorder on the splenic parenchyma or necrosis in histological analyzes. Qualitatively rare apoptotic events were observed, with no difference between control and irradiated animals. CONCLUSION: The high-energy X-ray, used in radiotherapy, modifies the splenic clearance, enhancing the amount of marginal zone macrophages containing colloid particles. This radiation was not associated with morphological changes, nor with necrosis or apoptosis of splenic tissue.

19.
Mol Ther ; 16(1): 146-53, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18071337

RESUMO

Oncolytic virotherapy is a promising strategy for treatment of malignancy, although its effectiveness is hampered by host antiviral inflammatory responses. The efficacy of treatment of oncolytic vesicular stomatitis virus (VSV) in rats bearing multifocal hepatocellular carcinoma (HCC) can be substantially elevated by antibody-mediated depletion of natural killer (NK) cells. In order to test the hypothesis that the oncotyic potency of VSV can be exponentially elevated by evasion of inflammatory responses in vivo, we constructed a recombinant VSV vector expressing equine herpes virus-1 glycoprotein G, which is a broad-spectrum viral chemokine binding protein (rVSV-gG). Infusion of rVSV-gG via the hepatic artery into immune-competent rats bearing syngeneic and multifocal HCC in their livers, resulted in a reduction of NK and NKT cells in the tumors and a 1-log enhancement in intratumoral virus titer in comparison with a reference rVSV vector. The treatment led to increased tumor necrosis and substantially prolonged animal survival without toxicities. These results indicate that rVSV-gG has the potential to be developed as an effective and safe oncolytic agent to treat patients with advanced HCC. Furthermore, the novel concept that oncolytic potency can be substantially enhanced by vector-mediated suppression of host antiviral inflammatory responses could have general applicability in the field of oncolytic virotherapy for cancer.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Vetores Genéticos/administração & dosagem , Mediadores da Inflamação/administração & dosagem , Terapia Viral Oncolítica , Vírus da Estomatite Vesicular Indiana/imunologia , Animais , Anti-Inflamatórios não Esteroides/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Linhagem Celular , Cricetinae , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Depleção Linfocítica , Masculino , Ratos , Ratos Endogâmicos BUF
20.
Cancer Res ; 67(17): 8285-92, 2007 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-17804743

RESUMO

Naturally occurring strains of Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently in clinical trials. Here, we have evaluated the possibility to enhance the cancer therapeutic potential of NDV by means of reverse genetics. Mice bearing s.c. implanted CT26 tumors were treated with intratumoral (i.t.) injections of a recombinant NDV modified to contain a highly fusogenic F protein. These treated mice exhibited significant reduction in tumor development compared with mice treated with the unmodified virus. Furthermore, mice in a CT26 metastatic tumor model treated with an i.v. injection of the genetically engineered NDV exhibited prolonged survival compared with wild-type control virus. In addition, we examined whether the oncolytic properties of NDV could be improved by expression of immunostimulatory molecules. In this regard, we engineered several NDVs to express granulocyte macrophage colony-stimulating factor, IFN-gamma, interleukin 2 (IL-2), or tumor necrosis factor alpha, and evaluated their therapeutic potential in an immunocompetent colon carcinoma tumor model. Mice bearing s.c. CT26 tumors treated with i.t. injections of recombinant NDV expressing IL-2 showed dramatic reductions in tumor growth, with a majority of the mice undergoing complete and long-lasting remission. Our data show the use of reverse genetics to develop enhanced recombinant NDV vectors as effective therapeutic agents for cancer treatment.


Assuntos
Carcinoma/terapia , Neoplasias do Colo/terapia , Engenharia Genética/métodos , Vírus da Doença de Newcastle/genética , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Carga Tumoral , Células Tumorais Cultivadas
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