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1.
Article in Chinese | WPRIM | ID: wpr-826376

ABSTRACT

To obtain ultrasound and thermal tomography images of breast cancer during its growth and to assess the value of thermal tomography in detecting breast cancer. Breast cancer models were established with NOD/SCID mice and SD rats. These animal models were examined by thermal tomography,plain ultrasound,and contrast-enhanced ultrasound. Tumor tissues were stained with CD34 to explore the relationship between tumor heat production and vascular pathology. Thermal tomography detected breast cancer 2-4 days earlier than ultrasound. The expression of CD34 in tumor tissues was increased,along with thickened,increased,and irregular blood vessels. Thermal tomography can detect early breast cancer and is a promising tool for screening breast cancer.


Subject(s)
Animals , Breast Neoplasms , Diagnostic Imaging , Early Diagnosis , Mice , Mice, Inbred NOD , Mice, SCID , Neoplasms, Experimental , Diagnostic Imaging , Rats , Rats, Sprague-Dawley , Tomography , Ultrasonography, Mammary
2.
J. appl. oral sci ; 28: e20190558, 2020. graf
Article in English | LILACS, BBO | ID: biblio-1101249

ABSTRACT

Abstract Objective Ameloblastoma is a representative odontogenic tumor comprising several characteristic invasive forms, and its pathophysiology has not been sufficiently elucidated. A stable animal experimental model using immortalized cell lines is crucial to explain the factors causing differences among the subtypes of ameloblastoma, but this model has not yet been disclosed. In this study, a novel animal experimental model has been established, using immortalized human ameloblastoma-derived cell lines. Methodology Ameloblastoma cells suspended in Matrigel were subcutaneously transplanted into the heads of immunodeficient mice. Two immortalized human ameloblastoma cell lines were used: AM-1 cells derived from the plexiform type and AM-3 cells derived from the follicular type. The tissues were evaluated histologically 30, 60, and 90 days after transplantation. Results Tumor masses formed in all transplanted mice. In addition, the tumors formed in each group transplanted with different ameloblastoma cells were histologically distinct: the tumors in the group transplanted with AM-1 cells were similar to the plexiform type, and those in the group transplanted with AM-3-cells were similar to the follicular type. Conclusions A novel, stable animal experimental model of ameloblastoma was established using two cell lines derived from different subtypes of the tumor. This model can help clarify its pathophysiology and hasten the development of new ameloblastoma treatment strategies.


Subject(s)
Animals , Female , Mice , Ameloblastoma/pathology , Disease Models, Animal , Neoplasms, Experimental/pathology , Proteoglycans , Time Factors , Immunohistochemistry , Cells, Cultured , Reproducibility of Results , Collagen , Laminin , Cell Line, Tumor , Green Fluorescent Proteins/analysis , Drug Combinations
3.
Braz. j. biol ; 79(4): 629-638, Nov. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001489

ABSTRACT

Abstract Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 μg/μl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.


Resumo Antecedentes O carcinoma hepatocelular é a neoplasia primária mais frequente do fígado e é responsável por até um milhão de mortes em todo o mundo em um ano. Objetivos O objetivo do presente estudo foi avaliar a eficiência anticancerígena do rizoma de Bergenia ciliata contra a hepatocarcinogênese induzida por dietilnitrosoamina em camundongos balb c. Métodos Um por cento de dietilnitrosoamina foi preparado usando 99 ml de solução salina normal (0,9 por cento) à qual foi adicionado 1 ml de solução concentrada de dietilnitrosoamina (DEN) (0,01 μg / μl). O extrato de Bergenia ciliata foi preparado pela técnica de maceração. Os ratos foram classificados em quatro grupos: Grupo 1 grupo controle (N = 7) recebeu solução salina (3,5 mL / mg), grupo 2 (N = 14) recebeu dietilnitrosoamina (3,5 mL / mg) por via intraperitoneal uma vez por semana para oito semanas consecutivas, o grupo 3 (N = 7) recebeu extrato vegetal (150 mg / kg (peso corporal)) uma vez por semana, enquanto o grupo 4 (N = 7) recebeu combinação de dietilnitrosoamina (3,5 μl / mg) e extrato (150 mg / kg (peso corporal). Após oito semanas do grupo de indução DEN 2 ratos foram divididos em dois subgrupos contendo sete ratos cada, subgrupo 1 foi sacrificado enquanto subgrupo 2 foi tratado com extrato vegetal (150 mg / kg)) uma vez por semana durante oito semanas consecutivas. Resultados O modelo de camundongos hepatocelulares carcinômicos (CHC) injetados com DEN provocou declínio significativo nos níveis de albumina com elevações significativas concomitantes nos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato ehidrogenase (G6PDH) e bilirrubina. A administração intraperitoneal de B. ciliata como agente protetor produziu um aumento significativo nos níveis de albumina com uma diminuição significativa nos níveis dos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato desidrogenase (G6PDH) e bilirrubina. Conclusão Bergenia ciliata possui atividade antioxidante potente, capacidade de eliminação de radicais livres e propriedades anticancerígenas. Extratos de Bergenia ciliata podem fornecer uma base para o desenvolvimento de drogas anti-cancerígenas.


Subject(s)
Animals , Male , Rats , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/pathology , Diethylnitrosamine/pharmacology , Liver Neoplasms/chemically induced , Liver Neoplasms/pathology , Neoplasms, Experimental/chemically induced , Plant Extracts/pharmacology , Saxifragaceae , Alkylating Agents/pharmacology , Mice, Inbred BALB C
4.
Acta cir. bras ; 34(10): e201901001, Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054675

ABSTRACT

Abstract Purpose: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. Methods: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. Results: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. Conclusion: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.


Subject(s)
Animals , Female , Breast Neoplasms/drug therapy , Plant Extracts/pharmacology , Carcinoma/drug therapy , Bignoniaceae/chemistry , Neoplasms, Experimental/drug therapy , Antineoplastic Agents/pharmacology , Vincristine/pharmacology , Breast Neoplasms/pathology , Breast Neoplasms/diagnostic imaging , Carcinogens , Carcinoma/pathology , Carcinoma/diagnostic imaging , Catalase/analysis , Treatment Outcome , Rats, Wistar , Fluorodeoxyglucose F18 , 9,10-Dimethyl-1,2-benzanthracene , Glutathione Peroxidase/analysis , Antineoplastic Agents/therapeutic use
5.
Article in Chinese | WPRIM | ID: wpr-773126

ABSTRACT

Paclitaxel( PTX) is used as a broad spectrum anti-tumor medicine. However,serious drawbacks restrict clinical application of PTX. In this study,we prepared tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel( BSALC/DOPE-PTX) to study the effective antitumor activity. The in vivo targeting ability of the nanocarrier in tumor bearing nude mice was evaluated by using a Kodak in vivo imaging system FX PRO. The in vivo anti-tumor activity was evaluated in MDA-MB-231 tumor bearing mice,and representative sections were stained with hematoxylin and eosin( H&E),and examined by light microscopy. The results showed that DiR-loaded FA-BSA-LC/DOPE selectively targeted tumor,and had a relatively long residence in the tumor tissue. According to the in vivo anti-tumor activity study,FA-BSA-LC/DOPE-PTX exhibited an outstanding tumor inhibition effect with a tumor growth inhibition rate of 79.3%,and tumor tissue sections stained by hematoxylin and eosin( HE) showed severe necrosis areas and many dead cells with condensed nuclei in the FA-BSA-LC/DOPE-PTX group. Therefore,FA-BSA-LC/DOPE-PTX is a biocompatible,tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier,with a very marked anti-tumor activity in tumor-bearing mice in vivo.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic , Pharmacology , Cell Line, Tumor , Drug Carriers , Hydrogen-Ion Concentration , Lipoproteins , Mice , Mice, Nude , Nanoparticles , Neoplasms, Experimental , Drug Therapy , Paclitaxel , Pharmacology
6.
Article in Chinese | WPRIM | ID: wpr-773655

ABSTRACT

Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.


Subject(s)
Animals , Caprylates , Ginsenosides , Pharmacology , Mice , Molecular Structure , Neoplasms, Experimental , Drug Therapy , Saponins
7.
Acta cir. bras ; 34(3): e201900305, 2019. graf
Article in English | LILACS | ID: biblio-989062

ABSTRACT

Abstract Purpose: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). Methods: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. Results: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. Conclusion: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.


Subject(s)
Animals , Male , Rats , Stomach Neoplasms/drug therapy , Plant Extracts/therapeutic use , Adenocarcinoma/drug therapy , Usnea/chemistry , Acetates/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Rats, Wistar , Neoplasms, Experimental/drug therapy
8.
Acta cir. bras ; 34(12): e201901207, 2019. graf
Article in English | LILACS | ID: biblio-1054689

ABSTRACT

Abstract In the muscle invasive bladder cancer (MIBC) standard of care treatment only patients presenting a major pathological tumor response are more likely to show the established modest 5% absolute survival benefit at 5 years after cisplatin-based neoadjuvant chemotherapy (NAC). To overcome the drawbacks of a blind NAC (i.e. late cystectomy with unnecessary NAC adverse events) with potential to survival improvements, preclinical models of urothelial carcinoma have arisen in this generation as a way to pre-determine drug resistance even before therapy is targeted. The implantation of tumor specimens in the chorioallantoic membrane (MCA) of the chicken embryo results in a high-efficiency graft, thus allowing large-scale studies of patient-derived "tumor avatar". This article discusses a novel approach that exploits cancer multidrug resistance to provide personalized phenotype-based therapy utilizing the MIBC NAC dilemma.


Subject(s)
Humans , Animals , Urinary Bladder Neoplasms/drug therapy , Carcinoma/drug therapy , Urothelium/pathology , Chorioallantoic Membrane/pathology , Neoplasms, Experimental/drug therapy , Phenotype , Urinary Bladder Neoplasms/pathology , Carcinoma/pathology , Neoadjuvant Therapy , Medical Illustration , Neoplasm Seeding , Neoplasms, Experimental/pathology
9.
Electron. j. biotechnol ; 34: 22-28, july. 2018. ilus, graf
Article in English | LILACS | ID: biblio-1047453

ABSTRACT

Background: To examine the usefulness of green fluorescent protein (GFP) mice for studying the interactions between normal cells and tumor cells in a host, we used a melanoma model in such "green" mice [C57BL/6-Tg (CAG-EGFP)1Osb mice]. Mice were given a subcutaneous injection of B16-F10 cells, and the resultant primary tumors were removed. Then cells from individual tumors were cultured. Results: The proportion of EFGP+ cells was determined by fluorescence-activated cell sorting (FACS) and was 6.8% ± 3.2% (mean ± s.d.) on day 1 of culture, 0.6% ± 0.3% on day 2, and 0.02% ± 0.01% at day 7. In all cases, isolated cells grew at a constant rate, but fluorescence decreased over time and became undetectable on day 14. Cells were tested using PCR for the presence of an EGFP-specific sequence, and results were negative in all cases, thus indicating that the cells did not harbor the host's reporter gene. Cells were also tested for the presence of EGFP mRNA, which was consistently detected for 22 days after the start of culture. The tumorogenicity of the cultured cells was confirmed in GFP mice injected with cells from a selection of cultures. Conclusions: In a melanoma model in GFP mice, the detection of "green" cells in tumors was not equivalent to the detection of host-derived cells. Such "masking" was caused by a transient, but lasting, transfer of EGFP mRNA from the host's normal cells to tumor cells. Thus, an analysis of tumors postmortem by techniques that yield only a single snapshot can lead to incorrect interpretations and erroneous conclusions.


Subject(s)
Animals , Mice , Green Fluorescent Proteins , Melanoma , Neoplasm Transplantation , Polymerase Chain Reaction , Mice, Inbred C57BL , Neoplasms, Experimental
10.
Protein & Cell ; (12): 867-878, 2018.
Article in English | WPRIM | ID: wpr-757003

ABSTRACT

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.


Subject(s)
Animals , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasms, Experimental , Allergy and Immunology , Pathology , Therapeutics , Receptor, ErbB-2 , Allergy and Immunology , Receptors, Antigen, T-Cell , Allergy and Immunology , Stomach Neoplasms , Allergy and Immunology , Pathology , Therapeutics , Tumor Cells, Cultured
11.
Clinics ; 73(supl.1): e792s, 2018.
Article in English | LILACS | ID: biblio-974957

ABSTRACT

Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.


Subject(s)
Animals , Platelet Membrane Glycoproteins/antagonists & inhibitors , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Neoplasms, Experimental/therapy , Combined Modality Therapy/methods , Cell Line, Tumor , Neoplasms, Experimental/pathology , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/therapy
12.
Article in English | WPRIM | ID: wpr-296520

ABSTRACT

<p><b>OBJECTIVE</b>A subcutaneous transplantation tumor model of human HT-29 cells was established in nude mice to study the anticarcinogenic activities and apoptosis-regulatory mechanistic effect of aqueous extract of fermented barley with Lactobacillus plantarum dy-1 (LFBE).</p><p><b>METHODS</b>HT-29 cells were transplanted via subcutaneous injection of 1 × 107cells into the right flank of each nude mouse. Then, nude mice were treated for 30 days with LFBE (high-dose 2 g·kg-1·d-1; low-dose 1 g·kg-1·d-1) and for 7 days with 5-fluorouracil (5-FU, 25 g·kg-1·d-1) by gavage and intraperitoneal injection, respectively.</p><p><b>RESULTS</b>Tumor volume and weight decreased significantly in both groups of nude mice treated with LFBE. In addition, the cell apoptosis rate of the LFBE group was significantly higher than that of the control group and 5-FU groups as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot methods further confirmed these apoptosis-enhancing and growth-inhibiting effects. The involvement of LFBE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, caspase-3, and cyclinD1.</p><p><b>CONCLUSION</b>The results showed that LFBE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be used as a natural nutrient supplement or chemopreventive agent in the treatment of human colon cancer.</p>


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cell Proliferation , Cyclin D1 , Metabolism , Female , Fermentation , HT29 Cells , Hordeum , Chemistry , Humans , Lactobacillus plantarum , Mice, Nude , Neoplasm Transplantation , Neoplasms, Experimental , Drug Therapy , Metabolism , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Xenograft Model Antitumor Assays , bcl-2-Associated X Protein , Metabolism
13.
Protein & Cell ; (12): 514-526, 2017.
Article in English | WPRIM | ID: wpr-756974

ABSTRACT

The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB). The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the co-electroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effective method for generating high-quality T cells for adoptive immunotherapy.


Subject(s)
Animals , CD28 Antigens , Genetics , Allergy and Immunology , Electroporation , Humans , Immunity, Cellular , Interleukin-2 , Allergy and Immunology , K562 Cells , Mice , Muromonab-CD3 , Allergy and Immunology , Neoplasms, Experimental , Genetics , Allergy and Immunology , Pathology , RNA, Messenger , Genetics , Allergy and Immunology , T-Lymphocytes , Allergy and Immunology , Tumor Necrosis Factor Receptor Superfamily, Member 9 , Genetics , Allergy and Immunology
14.
Acta cir. bras ; 31(9): 597-601, Sept. 2016. tab, graf
Article in English | LILACS | ID: lil-795995

ABSTRACT

ABSTRACT PURPOSE: To assess antioxidant effects of açaí seed extract on anorexia-cachexia induced by Walker-256 tumor. METHODS: A population of 20 lab rats were distributed into four groups (n=5): Control Group (CG), which only received tumor inoculation. Experimental Group-100 (EG-100), with animals submitted to tumor inoculation and treated with seed extract in a 100 mg / ml concentration through gavage. Experimental Group-200 (EG-200), with animals submitted to tumor inoculation and treated with seed extract in a 200 mg / ml concentration. Placebo Group (GP), which received tumor inoculation and ethanol-water solution. We analyzed proteolysis, lipid peroxidation, tumor diameter and weight. RESULTS: Lipid peroxidation was representative only in the cerebral cortex, where there was more oxidative stress in rats treated with the extract (p = 0.0276). For proteolysis, there was less muscle damage in untreated rats (p = 0.0312). Only tumor diameter in treated rats was significantly lower (p = 0.0200) compared to untreated ones. CONCLUSIONS: The açaí seed extract showed no beneficial effect on the general framework of the cachectic syndrome in lab rats. However, some anticarcinogenic effects were observed in the tumor diameter and weight.


Subject(s)
Animals , Male , Seeds/chemistry , Cachexia/drug therapy , Plant Extracts/therapeutic use , Anorexia/drug therapy , Euterpe/chemistry , Antioxidants/pharmacology , Syndrome , Cachexia/etiology , Plant Extracts/pharmacology , Carcinoma 256, Walker/complications , Lipid Peroxidation/drug effects , Anorexia/etiology , Cerebral Cortex/enzymology , Analysis of Variance , Thiobarbituric Acid Reactive Substances/metabolism , Rats, Wistar , Oxidative Stress/drug effects , Neoplasms, Experimental/complications , Antioxidants/analysis
15.
Rev. Col. Bras. Cir ; 43(2): 72-79, Mar.-Apr. 2016. tab, graf
Article in English | LILACS | ID: lil-782917

ABSTRACT

ABSTRACT Objective: to evaluate the influence of Ki-67 and P16INK4a proteins immunohistochemical expressions on the clinical and morphological parameters of perioral squamous cell carcinoma induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) in mice. Methods: we topically induced the lesions in the oral commissure of ten Swiss mice for 20 weeks, determining the time to tumors onset and the average tumor volume up to 26 weeks. In histopathological analysis, the variables studied were histological malignancy grade and the immunohistochemical expression of Ki-67 and P16INK4a proteins. The correlation between variables was determined by application of the Spearman correlation test. Results: the mean time to onset of perioral lesions was 21.1 ± 2.13 weeks; mean tumor volume was 555.91 ± 205.52 mm3. Of the induced tumors, 80% were classified as low score and 20% high score. There was diffuse positivity for Ki-67 in 100% of lesions - Proliferation Index (PI) of 50.1 ± 18.0. There was a strong direct correlation between Ki-67 immunoreactivity and tumor volume (R = 0.702) and a low correlation with the malignancy score (R = 0.486). The P16INK4a protein expression was heterogeneous, showing a weak correlation with tumor volume (R = 0.334). There was no correlation between the immunohistochemical expression of the two proteins studied. Conclusion: in an experimental model of DMBA-induced perioral carcinogenesis, tumor progression was associated with the tumor proliferative fraction (Ki-67 positive cells) and with tumor histological grading, but not with P16INK4a expression.


RESUMO Objetivo: avaliar a influência da expressão imuno-histoquímica das proteínas Ki-67 e p16INK4a sobre parâmetros clínico-morfológicos em carcinomas espinocelulares periorais quimicamente induzidos com 9,10-dimetil-1,2-benzantraceno (DMBA) em modelo murino. Métodos: as lesões foram induzidas topicamente na comissura labial de dez camundongos Swiss durante 20 semanas, sendo determinado o momento de surgimento dos tumores e volume tumoral médio até 26 semanas. Na análise histopatológica, as variáveis estudadas foram gradação histológica de malignidade tumoral e expressão imuno-histoquímica das proteínas Ki-67 e p16INK4a. A correlação entre as variáveis estudadas foi determinada pela aplicação do teste de correlação de Spearman. Resultados: o tempo médio de surgimento das lesões periorais foi 21,1±2,13 semanas. Volume tumoral médio foi de 555,91±205,52mm3. Dos tumores produzidos, 80% foram classificados como de baixo escore e 20%, alto escore. Evidenciou-se positividade difusa para Ki-67 em 100% das lesões - índice de marcação (PI) de 50,1±18,0. Verificou-se correlação direta forte entre a imunoexpressão do Ki-67 e o volume tumoral (R=0,702) e fraca correlação com o escore de malignidade (R=0,486). A expressão da proteína p16INK4a foi heterogênea, mostrando fraca correlação com o volume tumoral (R=0,334). Não houve correlação entre a expressão imuno-histoquímica das duas proteínas estudadas. Conclusão: Em modelo experimental de carcinogênese perioral DMBA-induzida, a progressão tumoral está associada à fração proliferativa do tumor (células ki-67 positivas) e com a gradação histológica tumoral, porém não com a expressão da p16INK4a.


Subject(s)
Animals , Mouth Neoplasms/metabolism , Carcinoma, Squamous Cell/metabolism , Ki-67 Antigen/biosynthesis , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Neoplasms, Experimental/metabolism , Mouth Neoplasms/chemically induced , Carcinoma, Squamous Cell/chemically induced , Mice , Neoplasms, Experimental/chemically induced
16.
Int. j. morphol ; 34(1): 335-341, Mar. 2016. ilus
Article in Spanish | LILACS | ID: lil-780514

ABSTRACT

La angiogénesis y metástasis son eventos esenciales en el proceso de invasión tumoral. Su relación íntima los hace buenos blancos en la terapia antitumoral. El objetivo fue analizar el patrón de metástasis pulmonar y angiogénesis, luego de la aplicación del antiangiogénico Celecoxib microencapsulado en ácido poli(láctico-co-glicólico) en ratones. Se utilizó un modelo de tumor experimental, inducido por células TA3-MTX-R, en 18 ratones, separados en 3 grupos de 6 animales, los cuales fueron tratados con dos presentaciones de Celecoxib en administración intramuscular (Grupo Control; Grupo Cx 1000 ppm y Grupo Cx 1000 ppm+PLGA). Los ratones fueron sacrificados y procesados histológicamente para ser teñidos con H&E y Tricrómico de Arteta. El estudio reveló que el pulmón muestra una marcada heterogeneidad, y un patrón de metástasis perivascular; además, Celecoxib asociado a ácido poli(láctico-co-glicólico) redujo la invasión tumoral y angiogénesis en el pulmón. Los resultados son similares a descripciones parciales realizadas previamente y son comparables a otras líneas tumorales, siendo celecoxib/ácido poli(láctico-co-glicólico) un candidato potencial en la terapia antitumoral.


Angiogenesis and metastasis are critical events on the tumor invasion process. Their close association is related as a good target in antitumor therapy. The aim was to analyze lung metastasis pattern and angiogenesis following application of microencapsulated Celecoxib with poli(lactic-co-glycolic) acid in mice. An experimental tumor model was assessed, induced by TA3-MTX-R cells, in 18 mice, separated in 3 groups of 6 animals and treated with 2 intramuscular Celecoxib presentations (Group Control; Group Cx 1000 ppm and Group Cx 1000 ppm+PLGA). Mice were sacrificed and histologically processed to stain slides with H&E and Arteta Trichromic. The study revealed that the lung showed a significant heterogeneity, and a perivascular metastasis pattern; moreover, Celecoxib associated to poli(lactic-co-glycolic) acid reduces tumor invasion and pulmonary angiogenesis. The results are similar to partial previous descriptions and are comparable to other tumor lines, concluding that Celecoxib/poli(lactic-co-glycolic) acid is a potential candidate in antitumor therapy.


Subject(s)
Animals , Mice , Angiogenesis Inhibitors/administration & dosage , Celecoxib/administration & dosage , Lung Neoplasms/secondary , Neovascularization, Pathologic/drug therapy , Antineoplastic Agents/administration & dosage , Breast Neoplasms/pathology , Drug Delivery Systems , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Neoplasms, Experimental , Polyglycolic Acid
17.
Article in English | WPRIM | ID: wpr-285216

ABSTRACT

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.


Subject(s)
Animals , Carcinoma, Hepatocellular , General Surgery , Cell Line, Tumor , Flow Cytometry , Humans , Liver Neoplasms , General Surgery , Mice , Myeloid-Derived Suppressor Cells , Pathology , Neoplasms, Experimental , General Surgery , Spleen , General Surgery , Splenectomy , Methods
18.
Article in Chinese | WPRIM | ID: wpr-749701

ABSTRACT

OBJECTIVE@#To investigate the effects of combined inhibition of signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1α (HIF-1α) in the enhancement of chemosensitivity of the model of human laryngeal squamous cacinoma in nude mice.@*METHOD@#Model nude mice were divided into six groups randomly: control group(A) , cisplatin group(B) , cisplatin and AG490 group(C) , cisplatin and HIF-1α⁻/⁻ group (D), cisplatin combined AG490 and HIF-1α⁻/⁻ group (E), HIF-1α⁻/⁻ group (F) (only in calculating tumor inhibition rate). 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1α was detected by immunocytochemical method. Western blot was used to detect the expression of p-STAT3.@*RESULT@#The expression of HIF-1α in group C and group D were lower than that in group B, and there were significant difference respectively (t₁ = 2.782, t₂ = 3.873, P 0.05); The expression level of p-STAT3 in group E was significantly lower compared with that in group C and group D respectively (P < 0.01). Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively (t₁ = 5.509, P < 0.01; t₂ = 3.422, P < 0.05; t₃ = 2.718, P < 0.05 ). Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference respectively(t₁ = 8.307, P < 0.01; t₂ = 3.736, P < 0.05; t₃ = 4.524, P < 0.01).@*CONCLUSION@#Combined inhibition of STAT3 and HIF-1α could enhance chemo-sensitivity in the model of human laryngeal squamous cacinoma in nude mice.


Subject(s)
Animals , Antineoplastic Agents , Pharmacology , Carcinoma, Squamous Cell , Drug Therapy , Metabolism , Cisplatin , Pharmacology , Drug Resistance, Neoplasm , Hypoxia-Inducible Factor 1, alpha Subunit , Genetics , Metabolism , Ki-67 Antigen , Metabolism , Laryngeal Neoplasms , Drug Therapy , Metabolism , Mice , Mice, Nude , Neoplasms, Experimental , Drug Therapy , Metabolism , STAT3 Transcription Factor , Genetics , Metabolism , Tyrphostins , Pharmacology
19.
Braz. j. med. biol. res ; 49(7): e5263, 2016. graf
Article in English | LILACS | ID: lil-785060

ABSTRACT

B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.


Subject(s)
Humans , Animals , Mice , Adenocarcinoma/pathology , B7-H1 Antigen/analysis , Cell Proliferation , Lung Neoplasms/pathology , T-Lymphocytes/pathology , A549 Cells , Antibodies, Neoplasm/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Cells, Cultured , Flow Cytometry , Immunotherapy/methods , Mice, Inbred C57BL , Neoplasms, Experimental , Splenic Neoplasms/pathology , Xenograft Model Antitumor Assays
20.
Rev. latinoam. enferm. (Online) ; 23(4): 651-659, July-Aug. 2015. tab, ilus
Article in English | LILACS, BDENF | ID: lil-761699

ABSTRACT

AbstractObjective: to perform the translation into Brazilian Portuguese and cultural adaptation of the Face, Legs, Activity, Cry, Consolability revised (FLACCr) scale, with children under 18 years old, affected by cerebral palsy, presenting or not cognitive impairment and unable to report their pain.Method: methodological development study of translation into Portuguese and cultural adaptation of the FLACCr. After approval by the ethics committee, the process aimed at translation and back-translation, evaluation of translation and back-translation using the Delphi technique and assessment of cultural equivalence. The process included the five categories of the scale and the four application instructions, considering levels of agreement equal to or greater than 80%.Results: it was necessary three rounds of the Delphi technique to achieve consensus among experts. The agreement achieved for the five categories was: Face 95.5%, Legs 90%, Activity 94.4%, Cry 94.4% and Consolability 99.4%. The four instructions achieved the following consensus levels: 1st 99.1%, 2nd 99.2%, 3rd 99.1% and 4th 98.3%.Conclusion: the method enabled the translation and cultural adaptation of the FLACCr. This is a study able to expand the knowledge of Brazilian professionals on pain assessment in children with CP.


ResumoObjetivo:realizar a tradução para a língua portuguesa do Brasil e adaptação cultural da escala Face, Legs, Activity, Cry, Consolability revised(FLACCr), com crianças de até 18 anos de idade, acometidas por paralisia cerebral, apresentando ou não comprometimento cognitivo e impossibilitadas de relatar sua dor.Método:estudo de desenvolvimento metodológico de tradução para o português e adaptação cultural da FLACCr. Após aprovação do comitê de ética, o processo contemplou tradução e retrotradução, avaliação da tradução e da retrotradução utilizando a técnica de Delphi e avaliação da equivalência cultural. O processo incluiu as cinco categorias da escala e as quatro orientações de aplicação, considerando nível de concordância igual ou maior a 80%.Resultados:foram necessários três ciclos da técnica de Delphi para consenso entre os juízes. A concordância obtida para as cinco categorias foi: Face 95,5%, Pernas 90%, Atividade 94,4%, Choro 94,4% e Consolabilidade 99,4%. As quatro orientações alcançaram os seguintes níveis de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% e 4ª 98,3%.Conclusão:o método possibilitou o desenvolvimento da tradução e adaptação cultural da FLACCr. Sendo um estudo capaz de ampliar o conhecimento de profissionais brasileiros sobre a avaliação da dor em crianças com PC.


ResumenObjetivo:realizar la traducción para el portugués de Brasil y la adaptación cultural de la escala, Face, Legs, Activity, Cry, Consolability revised(FLACCr), con niños menores de 18 años de edad, afectados por la parálisis cerebral, presentando o no deterioro cognitivo y que no pueden comunicar su dolor.Método:estudio de desarrollo metodológico de traducción al portugués y adaptación cultural de la FLACCr. Después de la aprobación por el comité de ética, el proceso incluyó la traducción y retrotraducción, evaluación de la traducción y retrotraducción utilizando la técnica Delphi y evaluación de la equivalencia cultural. El proceso incluyó las cinco categorías de la escala y las cuatro orientaciones de aplicación, teniendo en cuenta nivel de concordancia igual o superior al 80%.Resultados:fueron necesarios tres ciclos de la técnica Delphi para el consenso entre los jueces. La concordancia obtenida para las cinco categorías fue: Cara 95,5%, Piernas 90%, Actividad 94,4%, Llanto 94,4% y Capacidad de Consuelo 99,4%. Las cuatro orientaciones alcanzaron los siguientes niveles de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% y 4ª 98,3%.Conclusión:el método permitió el desarrollo de la traducción y adaptación cultural de la FLACCr. Este estudio fue capaz de aumentar el conocimiento de los profesionales brasileños en la evaluación del dolor en niños con PC.


Subject(s)
Animals , Rats , Graft Rejection/immunology , Neoplasms, Experimental/immunology , Cell Line, Tumor , Graft Rejection/genetics , Graft Rejection/pathology , Neoplasm Transplantation , Neoplasms, Experimental/genetics , Neoplasms, Experimental/pathology , Rats, Inbred Lew , Rats, Wistar
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