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1.
Ticks Tick Borne Dis ; 15(4): 102346, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38643720

RESUMO

Bovine anaplasmosis is a tick-borne disease caused by Anaplasma marginale in the United States. The objective of this study was to use a survey tool to generate information for beef operations in California on anaplasmosis prevention and control management, including to what extent management activities were informed by perceived herd-level exposure to A. marginale infection or occurrence of clinical anaplasmosis cases. We mailed 2,621 questionnaires with questions on Anaplasma status, herd demographics, anaplasmosis control and prevention measures, and environmental factors to beef ranchers in California in October 2020. Survey-weighted chi-square tests were used to compare management differences according to perceived Anaplasma infection status. Generalized estimating equations (GEEs) were used to analyze whether region of California, management practices, or environmental factors were associated with reported clinical cases of anaplasmosis in the previous five years. A total of 466 questionnaires describing 749 herds were obtained and used in this study. Use of management measures, including deliberate exposure of calves to ticks, vaccination for Anaplasma, infection control through antibiotics in feed, maintaining a completely closed herd, blood testing for Anaplasma on all herd additions, and taking no anaplasmosis control and prevention measures, were significantly different between herds with or without perceived A. marginale infection based on producers' self-declared status. The overall perceived prevalence for Anaplasma infection and reported clinical cases of anaplasmosis at the herd level was 26.0 % (95 % CI: 24.3-27.7 %) and 17.1 % (95 % CI: 15.6-18.6 %) respectively, with the highest perceived infection and case numbers reported in the Central Coast region. In the GEE model, higher odds of reporting clinical cases of anaplasmosis in the previous five years were observed in cattle located in the Central Coast region, cattle within a large herd, cattle that are treated with tick/fly control, cattle in a completely closed herd, and cattle receiving Anaplasma vaccine. Anaplasma infection and bovine anaplasmosis status may be underestimated in beef herds in California based on previous study results. Changing needles between cattle after injections and conducting blood testing for Anaplasma on herd additions are important Anaplasma management measures that are infrequently implemented in beef herds in California. The results show a need for producer education to improve producers' awareness of bovine anaplasmosis and implement proper measures for disease control and prevention.


Assuntos
Anaplasma marginale , Anaplasmose , Doenças dos Bovinos , Animais , Bovinos , Anaplasmose/epidemiologia , Anaplasmose/microbiologia , California/epidemiologia , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/prevenção & controle , Masculino , Feminino , Inquéritos e Questionários
2.
Polymers (Basel) ; 15(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37959962

RESUMO

The preparation of poly (vinyl alcohol)/chitosan/ZnO (PVA/Cs/ZnO) nanocomposite films as bioactive nanocomposites was implemented through an environmentally friendly approach that included mixing, solution pouring, and solvent evaporation. The nanocomposite films were characterized using various techniques such as X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and UV-Vis spectroscopy. The XRD study revealed the encapsulation of nanoparticles by the PVA/Cs blend matrix. The DSC results showed that the addition of ZnO NPs increased glass transition and melting temperature values of the PVA/Cs blend. ATR-FTIR spectra detected an irregular shift (either red or blue) in some of the characteristic bands of the PVA/Cs nanocomposite, indicating the existence of intra/intermolecular hydrogen bonding creating an interaction between the OH groups of PVA/Cs and ZnO nanoparticles. A thermogravimetric (TGA) analysis demonstrated that the nanocomposites achieved better thermal resistance than a pure PVA/Cs blend and its thermal stability was enhanced with increasing concentration of ZnO nanoparticles. UV analysis showed that with an increase in the content of ZnO NPs, the optical bandgap of PVA/Cs was decreased from 4.43 eV to 3.55 eV and linear and nonlinear parameters were enhanced. Our optical results suggest the use of PVA/Cs/ZnO nanocomposite films for various optoelectronics applications. PVA/Cs/ZnO nanocomposites exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria. It was found that nanocomposite samples were more effective against Gram-positive compared to Gram-negative bacteria.

3.
Plants (Basel) ; 10(1)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33451098

RESUMO

In this work, two varieties of Anacyclus pyrethrum (L.) including Anacyclus pyrethrum var. pyrethrum (L.) and Anacyclus pyrethrum var. depressus (Ball) Maire were evaluated for their mineral and chemical compositions, total phenolic and flavonoid contents, and antimicrobial and antioxidant activities using hydroalcoholic extracts from their different parts (leaves, capitula, roots, and seeds). The phytochemical and mineral compositions were carried out using standard methods. The antioxidant activity was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azino-bis 3-ethylbenzothiazolin-6-sulfonic acid), and FRAP (ferric reducing antioxidant power) tests. The antimicrobial activity was assayed using the agar diffusion, minimum inhibitory concentration, and minimum bactericidal concentration methods. The results of the chemical analysis showed that both varieties contained interesting mineral and chemical compositions with potentially active compounds; among them, N-isobutyl-2,4-heptadiene-6-monoynamide and cinnamic acid were detected in the Anacyclus pyrethrum var. pyrethrum (L.) only while thiadiazolo [5,4-d] pyrimidin-7-amine and N-isobutyl-2,4-undecadiene-8,10-diynamide compounds were limited to the Anacyclus pyrethrum var. depressus (Ball) Maire. In vitro antioxidant and antimicrobial activities of the two varieties demonstrated that the different parts had prominent antioxidant and antimicrobial properties. The principal component analysis (PCA) showed great similarity in the activity of the leaves, capitula, and seeds of both plants and a high difference in roots. Anacyclus pyrethrum var. pyrethrum roots were characterized by a high content in phenols and flavonoids and better antibacterial activities compared to Anacyclus pyrethrum var. depressus (Ball) Maire roots, which were characterized by better antioxidant activities. From this study, it can be concluded that the two varieties of Anacyclus pyrethrum (L.) showed promising mineral and chemical compositions with antioxidant and antimicrobial properties.

4.
Gene ; 702: 153-157, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30922710

RESUMO

Irregular methylation, including DNA hypomethylation and/or promoter gene CpG hypermethylation, is involved in the pathogenesis of several solid tumors, including liver cancer. miRNAs are small, endogenous, noncoding RNAs that serve as posttranscriptional regulators of gene expression. Previous research has focused on identifying the factors that regulate the expression of miRNAs in hepatic carcinogenesis. The factors that regulate miRNA expression are not clear; in particular, the role of DNA methylation, an epigenetic regulatory factor that controls miRNA transcription, has not been clarified. The goal of this study is to explore our understanding of the mechanism by which HCC may develop and progress through identification of the role of epigenetically regulated miRNAs influences in the liver carcinogenesis. The current study included 60 patients who were well diagnosed as HCC patients. 60 patients who suffer from liver cirrhosis were also enrolled in the current study and 30 healthy control subjects who serve as control group. All patients will be subjected to: full clinical assessment, abdominal ultrasound, Blood sample will be withdrawn from every patients for both biochemical and serum detection of microRNAs (191-203 -335) by real time PCR. We found that all studied microRNAs were down regulated among HCC patients when compared to cirrhotic patients and controls (p value: 0.005, 0.005 and 0.001 for microRNAs 191, 203 and 335 respectively). Moreover, these microRNAs can discriminate cases of HCC from risky cirrhotic patients. We can conclude that downregulated microRNAs among HCC cases proposed a pattern to explain the role of DNA methylation on miRNA and gene expression in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Metilação de DNA , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade
5.
Med Vet Entomol ; 32(3): 304-310, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29498419

RESUMO

The northern fowl mite (NFM), Ornithonyssus sylviarum (Mesostigmata: Macronyssidae), is the primary blood-feeding ectoparasite found on poultry in the U.S.A. Three experiments were conducted in vitro to test the acaricidal properties of cade, garlic, lavender, lemongrass, pine and thyme essential oils against NFM, and to evaluate whether these effects are altered by adjusting oil application rates and application modality (direct vs. vapour contact). Applied at the rate of 0.21 mg/cm2 , the essential oils of cade, thyme, lemongrass and garlic resulted in higher NFM mortality at 24 h post-application than lavender and pine oils, and the untreated and ethanol-treated controls. Cade and thyme were the most consistent and fast-acting of the essential oils in terms of toxicity to NFM. Cade applied at 0.21 mg/cm2 and 0.11 mg/cm2 and thyme applied at 0.21 mg/cm2 were effective in eliminating NFM within 2 h through direct contact. The modality of application did not affect the efficacy of cade and thyme essential oils. The results suggest that essential oils may be utilized as alternatives to chemical pesticides and could be used as fumigants for the control of NFM.


Assuntos
Acaricidas , Infestações por Ácaros/veterinária , Ácaros , Óleos Voláteis , Doenças das Aves Domésticas/prevenção & controle , Controle de Ácaros e Carrapatos , Animais , Técnicas In Vitro , Infestações por Ácaros/prevenção & controle
6.
J Dairy Sci ; 101(1): 596-602, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29055543

RESUMO

To determine the effect of age at grouping on behavior, health, and production of dairy bull calves, 90 Holstein-Friesian bull calves were housed in individual pens until moved to 1 of 3 treatments. Calves were housed in groups of 3 calves at 3 d old (GH3), 7 d old (GH7), or 14 d old (GH14) until 7 wk of age. Ten groups of 3 calves for each treatment were used, with 5 pens/treatment in each of 2 replications (10 pens/treatment, 3 treatments, 3 calves/treatment; 90 calves total). Direct behavioral observations using instantaneous scan sampling every 10 min were conducted twice per week for 7 wk. At the same times, video data were recorded for continuous observations at feeding time to observe the overall activity of group-housed calves. Hip height, heart girth, and health scores were recorded weekly and body weight was recorded at the start and end of the study. Calves in GH3 spent more time playing and but more time cross-sucking and displacing other calves from milk bottles. Calves engaged in social interaction as early as 3 d of age, and social interactions between 3 to 6 wk of age increased markedly. Calves housed in GH14 vocalized more than did calves in GH7 and GH3. No difference was found between treatments in growth performance. Calf fecal, cough, and nasal and ocular discharge scores, differential leukocyte counts, and plasma cortisol concentrations were not affected by age at grouping. However, during the first week of grouping, when calves were moved from individual pens to group pens, some calves were unable to find their milk bottles and required guidance. In conclusion, these data show no adverse effects on health or performance and some benefits on social behavior for early (d 3) grouping of calves.


Assuntos
Bem-Estar do Animal , Ingestão de Alimentos , Abrigo para Animais , Hidrocortisona/sangue , Comportamento Social , Animais , Peso Corporal , Bovinos , Contagem de Leucócitos , Masculino
7.
Arch Med Res ; 47(5): 349-355, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27751368

RESUMO

BACKGROUND AND AIMS: Activation of telomerase reverse transcriptase (hTERT) has a role in liver carcinogenesis where telomerase is normally suppressed in most human somatic tissues after birth. In the current study we aimed to detect the significance of hTERT mRNA in early detection of hepatocellular carcinoma (HCC) and to determine the relationship between serum microRNA155 and telomerase expression. METHODS: Serum and liver tissue samples were collected from 40 patients (17 samples from patients with liver cirrhosis and 23 samples from patients with HCC) and 12 blood samples from healthy subjects were collected. Serum miRNA155 levels and blood and tissue hTERT mRNA were detected by real-time quantitative reverse-transcriptase PCR (RT-qPCR) among liver cirrhosis and HCC patients. Moreover, miR-155, blood and tissue hTERT levels were analyzed in relation to clinical and pathological features. RESULTS: Calculated expression of miRNA155 revealed that relative quantity (RQ) miR 155 was overexpressed in sera of HCC patients when compared to patients with liver cirrhosis and controls (p <0.0001). The median values of serum telomerase were significantly increased among HCC patients than in patients with liver cirrhosis and controls (p = 0.04). Moreover, tissue expression of telomerase was significantly higher in malignant tissue more than adjacent nonmalignant tissue among HCC patients (p = 0.02). It was also found that tissue expression of telomerase was significantly decreased in tissue of liver cirrhosis patients (p = 0.03). Interestingly, we found that blood telomerase was directly correlated with serum miRNA155 (p = 0.003). CONCLUSIONS: Both mir 155 and telomerase may have a role in development of HCC and mir 155 could regulate telomerase expression during liver carcinogenesis.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/sangue , Telomerase/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , Telomerase/genética
8.
Open Access Maced J Med Sci ; 4(1): 31-7, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-27275325

RESUMO

AIM: To determine the relation between serum microRNAs and apoptotic markers as regards development of HCC to understand the underlying mechanism of HCV related hepatocarcinogenesis. PATIENTS AND METHODS: A total of 65 serum samples (25 samples from controls, 20 samples from hepatitis and 20 samples from HCC patients) were collected for miRNAs (mir 21, mir 199-a, and mir 155) detection. Human Programmed cell death protein-4 (PDCD-4) and Human Cytochrome-C (CYT-C) were determined. RESULTS: miRNAs 21 and 155 were over expressed in sera of patients with HCC compared to patients with chronic hepatitis (p < 0.0001). While serum means values of miR 199a was significantly decreased among HCC group patients when compared to patients with chronic hepatitis (p < 0.0001). The serum levels of PCDC4 and CYTC were increased in patients with HCC when compared to chronic hepatitis patients. They were also increased in patients with chronic hepatitis when compared to controls (p < 0.05, significant). There was direct correlations between apoptotic markers and oncomirs miRNAs 21 and 155 while apoptotic markers were inversely correlated with miRNA 199-a. CONCLUSION: Both microRNAs and apoptotic markers have roles in HCC pathogenesis. It seems that oncogenic microRNAs induce liver carcinogenesis in HCV patients irrespective of suppression of apoptosis.

9.
Gene ; 575(1): 66-70, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26302751

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the serum and tissue expression of miR 21 and miR 199-a to be applied as early detectors for HCC. METHODS: A total of 40 serum and tissue samples (17 samples from chronic hepatitis and 23 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-21 and miR-199-a) were detected by real time quantitative reverse-transcriptase PCR (RT-qPCR) in sera and tissues of chronic hepatitis and HCC patients. Besides, miR-21 and miR-199-a levels in relation to clinical and pathological factors were explored. RESULTS: We found that the expression of serum miR-21 was distinctly increased in HCC compared with chronic hepatitis (P<0.001). miR 199-a was distinctly decreased in HCC compared with chronic hepatitis (P<0.001). In addition, median of miR 21 was increased in malignant when compared to adjacent non-malignant tissues without significant differences (P=0.191) while miR 199-a was significantly decreased in malignant when compared to adjacent nonmalignant tissues (P<0.001). ROC analysis showed that miR-21 and miR-199-a might be potential biomarkers for HCC. CONCLUSIONS: In conclusion, the expression of miR-21 was significantly up-regulated and miR-199-a was significantly down regulated in serum of patients with HCC. Due to their reasonable sensitivity and specificity for disease progression, miR-21 and miR-199-a could be used as potential circulating biomarkers for HCC.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs/biossíntese , RNA Neoplásico/biossíntese , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
10.
Vet Immunol Immunopathol ; 164(3-4): 118-26, 2015 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-25746346

RESUMO

Chronic stressors are a major health and well-being issue in animals. Immune status of animals under chronic stress is compromised, thus reducing disease resistance and compromising well-being of the animal. The objective of this study was to determine the influence of group size of veal calves on immune status and leukocyte mRNA expression of acute phase cytokines, toll-like receptor 4 (TLR4) and tachykinin 1 (TAC1) over a five-month finishing period. Holstein bull calves (n=168), 44±3 days of age were assigned to one of three treatments; 2, 4, or 8 calves/pen (pen space allowance of 1.82m(2)/calf). Jugular blood samples were collected at the day of grouping and then monthly for 4 months. The differential leukocyte counts were determined and mRNA was extracted from the leukocytes. Reverse transcription-qPCR was used to measure the gene expression of interleukin-1 (IL-1ß), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor (TNF-α), TLR4, and TAC1 in leukocytes. Health was evaluated before grouping and monthly for 4 months. On the 1st month after grouping, veal calves that were housed in groups of 8 have greater expression of IL-1ß mRNA than calves housed in groups of 4 or 2 (treatment×month, P=0.04). Also at 1 month, groups of 8 had greater TAC1 expression (P<0.05) than calves housed in groups of 4 or 2. However, the expression of IL-1Ra, TNF-α, and TLR4 were not influenced by group size. In the first month of the trial, calves in groups of 8 coughed more (P<0.05) than calves in groups of 2 and coughed more than calves in groups of 4 and 2 during the 2nd month (treatment×month, P=0.03). Calves housed in groups of 8 tended to have greater neutrophil percentage (P=0.09), neutrophil to lymphocyte ratio (P=0.06), and had lower lymphocyte percentage (P=0.06) than those housed in groups of 4 or 2. In conclusion, the number of veal calves in a group, given the same space during the finishing period did not alter IL-1Ra, TNF-α, and TLR4 mRNA expression. However, housing of calves in groups of 8 was associated with greater expression of IL-1ß and TAC1 mRNA in peripheral blood leukocytes, and coughing during the first 2 months after grouping. Therefore, housing of veal calves in larger groups may lead to greater susceptibility to respiratory disease and stress.


Assuntos
Bovinos/imunologia , Citocinas/genética , Abrigo para Animais , RNA Mensageiro/análise , Taquicininas/genética , Receptor 4 Toll-Like/genética , Animais , Contagem de Leucócitos , Estresse Psicológico/imunologia
11.
J Genet Eng Biotechnol ; 13(2): 157-163, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30647579

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death in the whole world. Apoptosis is a fundamental process controlling cell death and plays a critical role in normal development of multicellular organisms. When abnormalities occur in apoptosis, a variety of diseases are caused, including cancer. The aim of the current study was to determine the serum expression of Cytochrome c and PDCD4 among patients with hepatocellular carcinoma and chronic hepatitis. PATIENTS AND METHODS: A total of 40 serum and tissue samples (17 samples from chronic hepatitis and 23 samples from HCC patients) were collected. Apoptotic markers in serum were carried out using the quantitative sandwich enzyme immunoassay technique. RESULTS: We found that serum levels of PCDC4 and Cytochrome c were increased in patients with HCC when compared to chronic hepatitis patients. They were also increased in patients with chronic hepatitis when compared to controls (p < 0.05, significant). Analyzing the impact of HCC characters on serum values of PDCD4 and Cytochrome c revealed that the mean values of both PDCD4 and Cytochrome c are significantly higher in cases with single lesion of HCC (p < 0.05, significant). Right lobe location of HCC lesions has the highest mean values of PDCD4 (p < 0.05, significant). As regards grade of differentiation, grade П has higher mean values of Cytochrome c (p < 0.05, significant). CONCLUSION: Serum levels of Cytochrome c and PDCD4 are increased in patients with cirrhosis and hepatocellular carcinoma and could be used as diagnostic aid for HCC.

12.
J Anim Sci ; 91(11): 5455-65, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23989884

RESUMO

The objective of this study was to investigate the effect of group size on behavior, growth, health, and welfare of veal calves. Holstein-Friesian bull calves (n=168; 44±3 d of age) were assigned randomly to 1 of 3 treatments of group housing with 2, 4, or 8 calves per pen. The pens used for housing were 3 by 1.20 m (2 calves per pen), 3 by 2.40 m (4 calves per pen), and 3 by 4.80 m (8 calves per pen), supplying a total pen space allowance of 1.82 m2/calf, regardless of pen size. Behavior was recorded from video data throughout the day from 0700 to 1900 h during a single day each month for 5 mo using scan sampling every 5 min within 30-min observation sessions. On d 0, 1, 5, 14, 42, and 70 after grouping, continuous focal sampling around feeding time (30-min intervals before, during, and after feeding) focused on oral and aggressive behaviors. Calves housed in large groups (4 or 8 calves per pen) showed more (P≤0.001) conspecific contact, walking, and standing and less (P<0.001) manipulation of objects, self-licking, and lying when compared to calves housed in small groups (2 calves per pen). Group size had no effect on play behavior (P=0.11) throughout the experiment. During feeding times group size had no (P≥0.07) effect on any behavioral patterns except for duration of conspecific contact (P<0.01). Aggression at feeding time was not (P>0.23) affected by treatment. Group size treatments were similar for hip height change (P=0.41) and heart girth change (P=0.18) over the duration of the experiment; however, both hip height and heart girth increased (P=0.001) with calf age. During mo 1, calves in groups of 8 or 4 coughed more than calves in groups of 2 whereas calves in groups of 8 coughed more than calves in groups of 4 or 2 in mo 2 (treatment×month, P=0.03). Furthermore, during mo 4, calves in groups of 8 had less nasal discharge than calves in groups of 2 or 4 (treatment×month, P=0.02). Ocular discharge, ears, and fecal scores did not differ (P≥0.05) among treatments. Plasma cortisol was not (P≥0.37) affected by group size. The number of veal calves in a group when given the same space did not affect production and physiological indicators of welfare but had a transient effect on health during the 5-mo finishing period. If increased play and social contact and decreased aggression are considered as primary indicators of welfare, group size did not alter calf welfare.


Assuntos
Criação de Animais Domésticos/métodos , Bem-Estar do Animal , Comportamento Animal/fisiologia , Animais , Bovinos , Hidrocortisona/sangue , Masculino , Comportamento Social , Estresse Fisiológico/fisiologia , Aumento de Peso
13.
Gene Ther ; 18(10): 969-78, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21512508

RESUMO

We previously identified the mouse and human Glipr1 and GLIPR1/RTVP-1 genes, respectively, as direct p53 targets with proapoptotic activities in various cancer cell lines, including prostate cancer (PCa). Intratumoral injection of an adenoviral vector capable of efficient transduction and expression of Glipr1 (AdGlipr1) yielded promising therapeutic results in an orthotopic, metastatic mouse model of PCa. AdGlipr1-transduced macrophages (Mφ/Glipr1) generated greater surface expression of CD40, CD80 and major histocompatibility complex class II molecules and greater production of interleukin 12 (IL-12) and IL-6 in vitro than control macrophages did. Mechanistic analysis indicated that increased production of IL-12 in Mφ/Glipr1 depends on activation of the p38 signaling cascade. Mφ/Glipr1 injected into orthotopic 178-2BMA tumors in vivo resulted in significantly suppressed prostate tumor growth and spontaneous lung metastases and longer survival relative to those observed in control-treated mice. Furthermore, these preclinical data indicate the generation of systemic natural killer cell activity and tumor-specific cytotoxic T lymphocyte responses. Trafficking studies confirmed that intratumorally injected Mφ/Glipr1 could migrate to draining lymph nodes. Overall, our data suggest that this novel gene-modified cell approach is an effective treatment avenue that induces antitumor immune responses in preclinical studies.


Assuntos
Terapia Genética/métodos , Macrófagos/metabolismo , Metástase Neoplásica/prevenção & controle , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Proteínas/genética , Adenoviridae , Animais , Antígeno B7-1/metabolismo , Antígenos CD40/metabolismo , Vetores Genéticos/administração & dosagem , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Células Matadoras Naturais/imunologia , Cinética , Masculino , Camundongos , Neoplasias da Próstata/imunologia , Linfócitos T Citotóxicos/imunologia
14.
Gene Ther ; 14(3): 227-36, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17024109

RESUMO

We investigated the potential benefits of combining adenoviral vector mediated in situ interleukin-12 (AdmIL-12) gene therapy with radiation therapy (XRT) to enhance therapeutic efficacy. In a metastatic mouse prostate cancer cell line, 178-2 BMA, AdmIL-12+XRT demonstrated enhanced therapeutic activities in vitro as determined by clonogenic survival, apoptosis, and mIL-12 levels. At the molecular level, increased expression of tumor necrosis factor-alpha mRNA was specific for the combined therapy. In a subcutaneous 178-2 BMA in vivo model, the combination of AdmIL-12+XRT produced statistically significant tumor growth suppression compared to control vector Adbetagal, Adbetagal XRT, or AdmIL-12 as monotherapy. In addition, significant prolongation of survival was demonstrated for the combination of AdmIL-12+XRT. The combination of AdmIL-12+XRT significantly suppressed both spontaneous and pre-established lung metastases, and led to a prolonged elevation of serum IL-12 and significantly increased natural killer (NK) activities. Importantly, in vivo depletion of NK cells resulted in significant attenuation of the antimetastatic activities of AdmIL-12 alone or AdmIL-12+XRT. These combined effects suggest that AdIL-12 gene therapy together with radiotherapy may achieve maximal tumor control (both local and systemic) in selected prostate cancer patients via radio-gene therapy induced local cytotoxicity and local and systemic antitumor immunity.


Assuntos
Adenoviridae/genética , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Interleucina-12/genética , Neoplasias Pulmonares/secundário , Neoplasias da Próstata/terapia , Animais , Linhagem Celular Tumoral , Terapia Combinada , Vetores Genéticos/genética , Humanos , Injeções Intralesionais , Interleucina-12/sangue , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Masculino , Camundongos , Camundongos Mutantes , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/radioterapia , Transdução Genética/métodos , Fator de Necrose Tumoral alfa/metabolismo
15.
Cancer Gene Ther ; 13(7): 658-63, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16485011

RESUMO

We previously identified a novel p53 target gene, RTVP-1, that possesses unique cytotoxic and immunostimulatory activities which make it potentially useful for cancer gene therapy. To test the therapeutic potential of RTVP-1 in a gene-modified tumor cell-based vaccine model, we used an adenoviral vector capable of efficient transduction and expression of RTVP-1 (AdRTVP-1), together with a highly metastatic mouse prostate cancer cell line (178-2 BMA). A vaccine was prepared with 178-2 BMA cells transduced with AdRTVP-1 or a control adenoviral vector expressing beta-galactosidase (Adbetagal). After irradiation of the cells, syngeneic 129/Sv mice were vaccinated three times at weekly intervals. After 3 weeks, they were challenged with orthotopic 178-2 BMA cells. After 21 days, fewer than 60% of the RTVP-1-cell-vaccinated mice developed tumors compared to 100% of the control mice. The RTVP-1-cell vaccine significantly reduced primary tumor wet weight compared with control Adbetagal-cell vaccine (P<0.0001 at 7 and 14 days). Experimental metastasis to lung was also significantly reduced (P=0.0377), and survival significantly increased (P=0.0002). In addition, significantly increased NK and CTL activities were demonstrated in the AdRTVP-1-cell-vaccinated mice. These findings indicate that RTVP-1 gene-modified cell-based vaccines may be useful in the prevention of recurrent prostate cancer.


Assuntos
Adenoviridae , Vacinas Anticâncer/uso terapêutico , Proteínas de Neoplasias , Proteínas do Tecido Nervoso , Neoplasias da Próstata/prevenção & controle , Animais , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Humanos , Masculino , Proteínas de Membrana , Camundongos , Proteínas de Neoplasias/imunologia , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Proteínas do Tecido Nervoso/imunologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Transdução Genética
16.
Afr. j. urol. (Online) ; 10(1): 1-8, 2004.
Artigo em Inglês | AIM (África) | ID: biblio-1257940

RESUMO

Objectives: To assess any additional benefits of the estimation of serum TGF Beta1 over serum PSA for differentiating localized from metastatic prostatic carcinoma. Patients and Methods: Forty-seven prostate cancer patients (23 with and 24 without metastases) and ten controls were included in the study. Serum PSA was estimated using the chemiluminescent immunometric assay; and serum TGF Beta1 was assessed using the enzyme immunoassay.Results: The mean serum PSA in the localized and metastatic disease groups were significantly higher than that in the control group (p0.001; p0.001 respectively); while the mean serum TGF Beta1 in the metastatic disease group only was significantly higher than in the control: group (p0.01). The mean serum PSA and TGF Beta1 in the metastatic disease group were significantly higher than the values in the localized disease group (p0.001; p0.001 respectively). Serum PSA was directly correlated with Gleason score in both patient groups (localized group: r


Assuntos
Produtos Biológicos , Biomarcadores Tumorais , Antígeno Prostático Específico , Neoplasias da Próstata , Fator de Crescimento Transformador beta
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