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1.
J. Health Biol. Sci. (Online) ; 8(1): 1-6, 01/01/2020. ilus
Article in Portuguese | LILACS | ID: biblio-1103689

ABSTRACT

Objetivo: devido ao consumo rotineiro do café pela população brasileira, o presente trabalho tem como objetivo avaliar o potencial carcinogênico de diferentes concentrações do café (Coffea arabica), por meio do Teste para Detecção de Tumor Epitelial em Drosophila melanogaster. Métodos: para avaliar o efeito carcinogênico do café, larvas de 3° estágio descendentes do cruzamento entre fêmeas virgens wts/TM3, sb¹ e machos mwh/mwh foram tratadas com diferentes concentrações de café comercial (100; 50; 25; 12,5 e 6,26 mg/mL). Após a exposição (48h) e o processo de metamorfose, as moscas adultas foram analisadas quanto à presença de tumor epitelial, e os grupos tratados foram comparados com o controle negativo (água ultrapura). A toxicidade do café foi mensurada por meio da taxa de moscas que sobreviveram a etapa de metamorfose após exposição. Resultados: foi observado diferença estatisticamente significativa na taxa de sobrevivência (p < 0,05) e na frequência de tumor epitelial total (p < 0,05) em moscas tratadas com 100 mg/mL de café, quando comparado ao controle negativo. Conclusões: o café, na concentração de 100 mg/mL, foi tóxico e carcinogênico para D. melanogaster.


Objective: Due to the routine consumption of coffee by the Brazilian population, the present work aims to evaluate the carcinogenic potential of different concentrations of coffee (Coffea arabica) through the Test for Epithelial Tumor Detection in Drosophila melanogaster. Methods: In order to evaluate the carcinogenic effect of coffee, third-stage larvae descended from the cross between virgin females wts/TM3, sb1 and males mwh/mwh were treated with different concentrations of commercial coffee (100, 50, 25, 12, 26 mg/mL). After exposure (48h) and the metamorphosis process, the adult flies were analyzed for the presence of an epithelial tumor and the treated groups were compared with the negative control (ultrapure water). Coffee toxicity was measured by the rate of flies that survived the post-exposure metamorphosis stage. Results: A statistically significant difference was observed in survival rate (p < 0.05) and frequency of total epithelial tumor (p < 0.05) in flies treated with 100 mg/mL of coffee, when compared to the negative control. Conclusions: Coffee at the concentration of 100 mg/mL was toxic and carcinogenic to D. melanogaster.


Subject(s)
Genotoxicity , Carcinogenicity Tests , Coffee
2.
Biol. Res ; 53: 13, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100919

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.


Subject(s)
Humans , Animals , Male , Middle Aged , Antigens, Tumor-Associated, Carbohydrate/genetics , Indians, South American/genetics , Gallbladder Neoplasms/genetics , Ascitic Fluid/metabolism , Tumor Cells, Cultured , Carcinogenicity Tests , Chile , DNA Fingerprinting , Tumor Suppressor Protein p53/genetics , Cisplatin/pharmacology , Mice, Inbred NOD , Clone Cells/drug effects , Clone Cells/metabolism , Sequence Analysis, RNA , Receptor, ErbB-2/genetics , Genes, erbB-2/genetics , Gene Expression Profiling , Cell Line, Tumor/drug effects , Cell Line, Tumor/metabolism , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Epithelial Cells/metabolism , Keratin-19/genetics , Keratin-7/genetics , Carcinogenesis/genetics , Gallbladder Neoplasms/metabolism , Antineoplastic Agents/pharmacology
3.
Article in English | WPRIM | ID: wpr-758894

ABSTRACT

With the increased use of cell therapy in the veterinary sector, there is a growing demand for the development of cell-based medicinal products and the determination of their safety. Currently, the Korean Animal and Plant Quarantine Agency has established a guideline for evaluating the safety of cell-based medicinal products for animal use. The guideline includes items related to definition, classification, management, manufacturing procedure and quality control (standard and test method), stability testing, toxicity testing, pharmacological testing, and performance of clinical trials. In addition, testing protocols related to safety assessment of animal cell-based products such as chromosome karyotyping, tumorigenicity testing, confirmatory testing of biodistribution and kinetics, and target animal safety testing are described in detail. Moreover, because cell-based medicinal products are novel therapies, deviations from traditional designs may be justified in order to obtain relevant safety information on the treatment. Additionally, this guideline can be amended on the basis of new scientific findings.


Subject(s)
Animals , Carcinogenicity Tests , Cell- and Tissue-Based Therapy , Classification , Karyotyping , Kinetics , Plants , Quality Control , Quarantine , Toxicity Tests
4.
Yonsei Medical Journal ; : 1166-1173, 2018.
Article in English | WPRIM | ID: wpr-718495

ABSTRACT

PURPOSE: Information on the possible role of the ribosomal protein S15a (RPS15a) in gastric cancer is scarce. The aim of this study was to evaluate the impact of RPS15a gene expression on the growth and cell cycle of gastric cancer cells in vitro and in vivo. MATERIALS AND METHODS: RPS15a mRNA expression was examined in cancer tissues and their corresponding adjacent normal tissues of 40 gastric adenocarcinoma patients. Next, RPS15a was knocked down using a lentivirus-mediated RNA interference (short hairpin RNA) system in the gastric cancer cell line BGC823. The effect of RPS15a knockdown was examined using CCK-8 assay, cell scratch test, colony formation assay, and flow cytometry. Finally, in nude mice, a tumorigenicity test was performed, and the tumor volume and weight were measured. RESULTS: RPS15a expression in tumor tissue was significantly greater than that in the adjacent normal tissue of gastric cancer patients. After RPS15a silencing, the BGC823 cell proliferation rate decreased significantly; most cells were arrested in the G0/G1 phase, cell growth was inhibited, and the migration rate was decreased. Colony formation assay showed that the number and size of clones in the RPS15a-silenced cells were fewer and smaller, compared to control cells. The nude mouse tumorigenicity test showed that RPS15a silencing had an inhibitory effect on tumor volume and mice weight. CONCLUSION: The present study found RPS15a expression to be higher in gastric tumors and its silencing in gastric cancer cells to inhibit the proliferation, growth, and migration thereof. Accordingly, RPS15a may be considered as a potential therapeutic target in gastric cancer.


Subject(s)
Adenocarcinoma , Animals , Carcinogenicity Tests , Cell Cycle , Cell Line , Cell Proliferation , Clone Cells , Flow Cytometry , Gene Expression , Gene Silencing , Humans , In Vitro Techniques , Mice , Mice, Nude , Ribosomal Proteins , RNA Interference , RNA, Messenger , Sincalide , Stomach Neoplasms , Tumor Burden
5.
Med. leg. Costa Rica ; 34(2): 43-48, sep.-dic. 2017. tab, ilus
Article in Spanish | LILACS | ID: biblio-894319

ABSTRACT

ResumenEl cáncer ocupacional es sin duda uno de los temas mas controversiales a valorar, dentro de la amplia gama de posibles pericias a las que puede enfrentarse en su diaria labor el médico forense. Es importante recalcar que el establecimiento del nexo de causalidad es la piedra angular cuando se habla de cáncer ocupacional, siendo de suma importancia que el médico forense se concentre en primera instancia en conocer la fisiopatología de cada una de las posibles patologías así como de sus posibles complicaciones radicando la importancia del médico forense en la capacidad de poder establecer o descartar la existencia de una relación de causalidad entre el diagnóstico clínico y los hechos narrados.


AbstractOccupational cancer is undoubtedly one of the most controversial issues to evaluate, within the wide range of possible expertise that can be faced in your daily work forensics. It is important to emphasize that the establishment of the causal link is the cornerstone when it comes to occupational cancer, and it is of the utmost importance that the forensic physician should concentrate in the first instance on the pathophysiology of each of the possible pathologies as well as their possible Complications rooting the importance of the medical examiner in the ability to establish or rule out the existence of a causal relationship between the clinical diagnosis and the events reported.


Subject(s)
Humans , Carcinogenicity Tests , Coroners and Medical Examiners , Occupational Cancer , Occupational Cancer/classification , Expert Testimony , Forensic Medicine
6.
São Paulo; s.n; s.n; 2017. 179 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-847737

ABSTRACT

O câncer de pulmão é a principal causa de morte relacionada ao câncer no mundo. Mutações em KRAS são altamente prevalentes no câncer e têm sido diretamente associadas ao processo tumorigênico. Apesar disso, até hoje todas as terapias visando inibir KRAS diretamente falharam e a caracterização de alvos indiretos, importantes para a oncogênese mediada por KRAS, é fundamental para o desenvolvimento de novas terapias contra o câncer de pulmão. Nós mostramos previamente que as quinases Aurora A (AURKA) e B (AURKB) são alvos a jusante de KRAS, importantes para o crescimento, viabilidade e oncogenicidade de linhagens celulares derivadas de tumores pulmonares mediados por KRAS. Aqui, nós aprofundamos os nossos estudos para melhor caracterizar AURKA e AURKB como potenciais alvos terapêuticos no câncer de pulmão. Os objetivos deste trabalho foram (1) investigar o mecanismo de perda de viabilidade induzido pela inibição de AURKA e/ou AURKB; (2) avaliar como a inibição de AURKA e/ou AURKB afeta propriedades oncogênicas relacionadas à agressividade tumoral; e (3) como a inibição destas quinases afeta o crescimento tumoral in vivo. Para tanto, nós utilizamos dois modelos celulares: (1) células A549 e H358, que apresentam mutações em KRAS, geneticamente modificadas para a expressão estável e induzível de shRNAs contra AURKA ou AURKB, e (2) células tumorais H1703, que não apresentam mutações em KRAS, geneticamente modificadas para a expressão induzível de KRASG12V, tratadas ou não com inibidores farmacológicos das quinases Aurora. A inibição farmacológica ou por interferência de RNA de AURKA e/ou AURKB em células H358 e A549 reduziu a proliferação celular, sendo esta inibição acompanhada de anomalias mitóticas, além de aneuploidia e poliploidia. A inibição destas quinases também induziu morte celular in vitro, tanto em mitose, quanto em interfase. Mais interessantemente, a inibição farmacológica dual de AURKA e AURKB induziu morte celular in vitro em células H1703, somente na presença de KRASG12V, indicando que a inibição das quinases Aurora afeta preferencialmente células portadoras de mutações em KRAS. Além disso, a inibição de AURKA e/ou AURKB reduziu propriedades malignas celulares relacionadas à agressividade tumoral, como migração, invasão e adesão. Finalmente, a inibição de AURKA por RNA de interferência em células A549 também reduziu a formação de tumores in vivo. Entretanto, como a inibição destas quinases levou a anomalias mitóticas e à instabilidade genética, nós resolvemos investigar se a inibição de TPX2, um substrato e ativador de AURKA, poderia ser uma abordagem alternativa para inibir esta via em câncer de pulmão induzido por KRAS. Primeiramente, nós observamos nos nossos modelos celulares que KRAS regula positivamente a expressão de TPX2. Além disso, a inibição de TPX2 em células pulmonares portadoras de KRAS oncogênica reduziu a viabilidade e proliferação celulares e induziu morte celular. Mais interessantemente, esses efeitos ocorreram preferencialmente em células que expressam KRAS oncogênica. Em conclusão, nossos resultados apoiam a hipótese de que a ativação de AURKA/TPX2 e AURKB por KRAS são eventos importantes no câncer de pulmão e sugerem a inibição destas vias, possivelmente em combinação com outras terapias citotóxicas, como uma nova abordagem terapêutica para o câncer de pulmão induzido por KRAS


Lung cancer is the leading cause of cancer-related deaths worldwide. KRAS mutations are widespread in lung cancer and have been causally linked to tumorigenesis. Nonetheless, therapies targeting KRAS directly have so far failed and characterization of indirect KRAS targets, which play important roles in KRAS-mediated oncogenesis, is crucial for the development of new therapies for lung cancer. We have previously shown that mitotic kinases Aurora A (AURKA) and B (AURKB) are downstream targets of oncogenic KRAS, important for the growth, viability, and oncogenicity of KRAS-transformed lung cancer cell lines. Here, we studied these kinases more in depth in order to better characterize them as potential therapeutical targets for KRAS-induced lung cancer. The aims of this study were (1) to investigate the mechanism leading to loss of viability upon AURKA and/or AURKB targeting; (2) to evaluate how AURKA and/or AURKB inhibition affects malignant properties associated with tumor aggressiveness; and (3) to determine whether AURKA and/or AURKB inhibition reduces KRAS-induced tumor growth in vivo. For that purpose, we used two cell-based models: (1) KRAS mutant A549 and H358 cells with stable and inducible shRNA-mediated knockdown of AURKA or AURKB, and (2) KRAS wildtype H1703 tumor cell lines, genetically engineered to inducibly express oncogenic KRASG12V treated or not with Aurora kinase pharmacological inhibitors. Targeting AURKA and/or AURKB pharmacologically or by RNA interference in H358 and A549 cells led to decreased cell proliferation, which was accompanied by mitotic abnormalities, leading to aneuploidy and hyperploidy. Aurora kinase targeting also induced cell death in vitro, both during mitosis and interphase. More importantly, AURKA and AURKB inhibition with a dual pharmacological inhibitor in H1703 cells induced cell death in vitro, but only in the presence of KRASG12V, indicating that Aurora kinase targeting affects preferentially lung cells harboring oncogenic KRAS. Furthermore, AURKA and/or AURKB targeting reduced malignant properties associated with tumor aggressiveness, such as cell migration, invasion and adhesion. Finally, AURKA targeting by RNA interference in A549 cells also reduced growth of xenograft tumors in vivo. Nonetheless, since Aurora targeting was associated with mitotic abnormalities and genetic instability, we decided to investigate if targeting TPX2, a substrate and an activator of AURKA, could constitute an alternative approach to targeting this pathway in KRAS-induced lung cancer. First, using our cell-based models, we determined that KRAS positively regulates TPX2 expression. In addition, TPX2 inhibition by RNA interference in KRAS-positive lung cells reduced cell viability and proliferation and induced cell death. Finally, these effects occurred preferentially in cells harboring oncogenic KRAS. In conclusion, our results support the hypothesis that activation of AURKA/TPX2 and AURKB by KRAS are important events in lung cancer and suggest inhibition of these pathways, possibly in combination with other cytotoxic therapies, as a new approach for KRAS-induced lung cancer therapy


Subject(s)
Aurora Kinase A/analysis , Aurora Kinase B/analysis , Oncogenes/genetics , A549 Cells , Carcinogenicity Tests , Cell Survival , Lung Neoplasms/complications , Research/methods
7.
Article in English | WPRIM | ID: wpr-197527

ABSTRACT

OBJECTIVES: A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. METHODS: Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor (“Survey on the work environment”) and by the Ministry of Environment (“Survey on the circulation amount of chemicals”). Risk was determined according to exposure in workplaces and chemical hazard. RESULTS: In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m³, as compared to the threshold exposure level of 5 mg/m³. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. CONCLUSIONS: DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below 5 mg/m³ and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP.


Subject(s)
Carcinogenicity Tests , Chemical Safety , Clergy , Dataset , Diethylhexyl Phthalate , Employment , Humans , Ink , Insecticides , International Agencies , Liver , Liver Neoplasms , Lung , Mass Screening , No-Observed-Adverse-Effect Level , Occupational Exposure , Occupational Health , Plasticizers , Plastics , Risk Assessment , Rodentia , Testis , Toxicity Tests, Acute , Ventilation
8.
Acta cir. bras ; 30(9): 624-631, Sep. 2015. tab, ilus
Article in English | LILACS | ID: lil-761497

ABSTRACT

ABSTRACTPURPOSE:To assess whether deoxycholic acid (DOC) and lithocholic acid (LCA) administered in a period of six months in a concentration of 0.25% may have a carcinogenic role in mice colon.METHODS:The study used C57BL6 female mice divided into four groups. The control group received a balanced diet and the others received diets supplemented with 0.25% DOC, 0.25% LCA and 0.125% DOC+0.125% LCA, respectively. After euthanasia, the lesions found in the resected gastrointestinal tracts were stained with hematoxylin-eosin and examined microscopically.RESULTS:No gastrointestinal tract changes were observed in the control group, while hyperplastic Peyer's patches in the small intestine, flat adenomas with mild dysplasia and chronic colitis at the level of the colon were found in all three test groups. The colonic lesions prevailed in the proximal colon. The highest number of flat adenoma lesions (8), hyperplasia of Peyer's patches (25) and chronic colitis (2) were found in mice fed with diet and LCA.CONCLUSION: Precancerous or cancerous pathological lesions could not be identified. Instead, adenomatous colonic injuries occurred in a shorter period of time (six months), compared to the reported data.


Subject(s)
Animals , Female , Bile Acids and Salts/toxicity , Carcinogens/toxicity , Cholagogues and Choleretics/toxicity , Colon/drug effects , Deoxycholic Acid/toxicity , Lithocholic Acid/toxicity , Adenoma/chemically induced , Carcinogenicity Tests , Colitis/chemically induced , Colon/pathology , Colonic Neoplasms/chemically induced , Disease Models, Animal , Feces/chemistry , Peyer's Patches/drug effects , Time Factors
9.
Acta cir. bras ; 29(7): 423-428, 07/2014. tab, graf
Article in English | LILACS | ID: lil-714578

ABSTRACT

PURPOSE: To evaluate the genotoxicity of propolis and L-lysine, as well as their effects on the possible cellular damage in erythroblasts (bone marrow) and leukocytes (peripheral blood) caused by the carcinogen BBN (n - butyl - n {4 - hydroxybutyl} nitrosamine) in rats subjected to bladder carcinogenesis and treated with green propolis and L-lysine. METHODS: One hundred and twenty five rats were distributed into the following groups: I, IIA, IIB, III, K, L M N, X, XI, XII and XIII. Groups I to X received BBN in drinking water for 14 weeks (wks). Group I was treated with intragastric (ig) propolis at 150 mg/kg body weight, for 44 wks, beginning 30 days before start of BBN. Groups IIA and III were treated with propolis (150 mg/kg), for 40 wks, subcutaneous (sc) and ig, respectively, beginning simultaneously with BBN. On the 32nd wk, the animals of groups L, M and N were treated ig with L-lysine (300 mg/kg), celecoxib (30 mg/kg) and propolis (300 mg/kg), respectively, up to the 40th wk. The groups that received only BBN (IIB and K) were treated with water, sc and orally, respectively, for 40 wks. Groups XI, XII and XIII received respectively propolis (150 mg/kg), L-lysine (150 mg/kg) and water ig for 40 wks. After 40 wks, the surviving animals were anesthetized and subjected to femoral bone marrow aspiration and blood collection from the aorta, for CA and MNT, respectively, for investigation of genotoxicity. RESULTS: Groups IIB and K, which received only BBN and water, showed the greatest DNA damage in peripheral leukocytes (CA) and largest number of micronuclei in bone marrow erythrocytes (MNT) in relation to all other groups that received BBN and lysine and/or propolis (p<0.001). CONCLUSIONS: Both propolis and L-lysine are effective in protecting against genotoxicity, as well not being genotoxic themselves toward the cells evaluated, at the doses and times administered and according to the two tests utilized. .


Subject(s)
Animals , Bone Marrow Cells/drug effects , Carcinogenesis/drug effects , Lymphocytes/drug effects , Lysine/pharmacology , Propolis/pharmacology , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Anticarcinogenic Agents/pharmacology , Carcinogenicity Tests , Comet Assay , DNA Damage , Micronucleus Tests , Rats, Wistar , Reference Values , Reproducibility of Results , Time Factors , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/prevention & control
10.
Rev. venez. oncol ; 25(2): 70-76, abr.-jun. 2013. tab
Article in Spanish | LILACS | ID: lil-718949

ABSTRACT

Estudio prospectivo para evaluar la técnica, utilidad de la plataforma genética de 70 genes mammaprint, para de clasificar pacientes con cáncer de mama en alto y bajo riesgo para recaída a distancia a 10 años, comparar resultados con factores de riesgo pronósticos y predictivos tradicionales. El mammaprint fue evaluado en muestras de piezas quirúrgicas en fresco de 16 pacientes tratadas entre mayo-octubre 2011, con diagnóstico de cáncer de mama estadios I-II. La muestra en fresco es tomada por los patólogos, enviada y procesada en Holanda. Grupo etario más frecuente: 61-70 años. 98,34% de éxito en toma de muestras, las cuales fueron satisfactorias para practicar técnica genética. El 80% de los casos fueron cirugías conservadoras de mama, 40% pacientes con tumores menores de 2 cm y menos de 3 ganglios positivos (86,6%). Pacientes con bajo riesgo y ganglios negativos fue el 26,66%, alto riesgo tenían de 1 a 3 ganglios positivos en un 40%. El subtipo molecular más frecuente 73% fue el luminal, correspondiendo al 53,33% de los pacientes de bajo riesgo. La técnica del perfil genético de 70 genes es una herramienta que puede ser realizada en nuestros centros, permite conocer el riesgo de recaída, identificar el subtipo molecular y disponer de una segunda opinión a los resultados de inmunhistoquímica de receptores hormonales y erb 2 neu, e individualizar el tratamiento de los pacientes con cáncer de mama.


Prospective study to evaluate the technical usefulness of the platform 70-gene mammaprint gene, in order to classify the breast cancer patients with high and low risk for relapse at 10 years distance, compare the results with prognostic risk factors and traditional predictors. The mammaprint was tested in samples from fresh surgical specimens of 16 patients treated in the period May to October 2011, service SOH-IVSS breast disease, diagnosed with breast cancer stages I-II. Fresh sample is taken by pathologists, then sent and processed in the Netherlands. Age group most frequently between 61 and 70 years of age. We obtained a 98.34% success in taking the samples, which were satisfactory for practicing genetic engineering. 80% of cases were breast-conserving surgeries, 40% of patients with tumors less than 2 cm and less than 3 positive nodes, 86.6% of cases. Patients with low-risk node-negative was 26.66%, high risk had 1 to 3 positive nodes in 40%. The most common molecular subtype was luminal 73%, corresponding to 53,33% of patients at low risk. The technique of the genetic profile of 70 genes or Mammaprintis a tool that can be performed in our centers, to understand the risk of relapse, identify the molecular subtype and havea second opinion as to the results of immunohistochemistry for hormone receptors and erb 2 neu, and individualize the treatment of patients with breast cancer.


Subject(s)
Humans , Female , Middle Aged , Immunohistochemistry , Breast Neoplasms/classification , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/prevention & control , Genetic Testing , Carcinogenicity Tests , Risk Assessment , Neoplasm Recurrence, Local/pathology , Medical Oncology
11.
Pakistan Journal of Pharmaceutical Sciences. 2013; 26 (1): 145-152
in English | IMEMR | ID: emr-146760

ABSTRACT

Chloroacetonitrile is a disinfectant by-product of chlorination of drinking water and is considered as a directacting mutagenic and carcinogenic agent. Time-course and dose-response studies were performed to examine the mechanism of chloroacetonitrile-induced hepatotoxicity. In the time-course study, animals were scarified at 2, 4, 6 and 12 h after a single oral dose of chloroacetonitrile [38 mg/kg, p.o.]. In the dose-response study, rats were scarified at 2 h after a single oral dose of chloroacetonitrile [9, 19, 38, and 76 mg/kg]. In the time-course study chloroacetonitrile induced a significant decrease of hepatic glutathione, and activities of glutathione-S-transferase, glutathione proxidase and superoxide dismutase accompanied with an increase of hepatic malondialdehyde, plasma cytokines [IL-6 and 10 and TNF-alpha], serum aminotransferases and total bilirubin after 2 h of administration. Maximal alteration of the estimated parameters was observed at 4 h and returned to normal value at 6 h and/or 12 h after chloroacetonitrile treatment. Moreover, the alterations in oxidant, antioxidant parameters, inflammatory cytokines and the liver function tests were dose dependant. Histopathological findings supported the biochemical results. These data indicate that the mechanism of chloroacetonitrile-induced hepatotoxicity may be mediated through depletion of antioxidants, induction of oxidative stress and inflammatory cytokines


Subject(s)
Acetonitriles/adverse effects , Halogenation/adverse effects , Mutagenicity Tests , Carcinogenicity Tests , Dose-Response Relationship, Drug , Glutathione , Superoxide Dismutase , Glutathione S-Transferase pi , Malondialdehyde , Antioxidants , Oxidative Stress , Interleukin-10 , Interleukin-6 , Tumor Necrosis Factor-alpha
12.
Arab Journal of Pharmaceutical Sciences. 2013; 4 (10): 103-112
in English, Arabic | IMEMR | ID: emr-139577

ABSTRACT

We seek in this study to assess the probability of contribution of tobacco to increase the chance that a person working in industry, where cadmium is its raw material, is achieved by cancer. A database was compiled from information recorded of a number of patients receiving treatment at Al Bayrouni hospital in Damascus during the past three years. The statistical probability analysis has shown the differential contribution of the two sources of affection, Tobacco and Industries polluted by cadmium, where a strong contribution of tobacco to the development of cancer of the lungs, gastrointestinal and the cervix, while the industry has marked a huge trace in the case of cancer of the kidneys and bladder, and a modest contribution in the case of prostate and ovary


Subject(s)
Humans , Tobacco Industry , Tobacco/adverse effects , Data Collection , Carcinogenicity Tests
13.
Article in English | IMSEAR | ID: sea-144790

ABSTRACT

Background & objectives: Prostate cancer (CaP) is the fifth most common cancer among Indian men. Tumour protein p53 (TP53) gene increases the fidelity of DNA replication and homologous recombination by transcriptional transactivation of mismatch repair (MMR) genes. DNA repair thus has a potential role in molecular carcinogenesis of CaP. The aim of the present study was to identify mutations, and polymorphisms in TP53 gene and MMR protein expression in CaP in Indian male population. Methods: TP53 codon 72 polymorphism was analysed in 105 CaP, 120 benign prostatic hyperplasia (BPH) cases and 106 normal controls. Mutational analysis of TP53 was done in DNA extracted from formalin fixed paraffin embedded tissue of 80 CaP and 24 BPH cases. Expression of MMR proteins viz. hMLH1, hMSH2, hPMS1 and hPMS2 was studied in 80 CaP, 15 prostatic intraepithelial neoplasia (PIN) and 15 BPH cases. Results: A somatic C/A variation at the intronic boundary of exon 7 in TP53 gene was observed in one each biopsy samples from CaP and BPH. A significant association of codon 72 TP53 Pro/Pro genotype was observed with the risk of CaP (OR, 2.59, P=0.02) and BPH (OR, 6.27, P<0.001). Immunohistochemical analysis of MMR proteins showed maximum loss of hPMS1 expression in cases of CaP and PIN while no loss in expression of MMR proteins was observed in BPH cases. The study also identified a significant loss of hPMS2 protein in poorly differentiated tumours (Gleason score >7) than in well differentiated tumours (Gleason score 3-6) (P<0.05). Interpretation & conclusions: The results of the present study demonstrate that TP53 codon 72 polymorphism plays significant role in the pathogenesis and susceptibility to CaP and BPH. Also, an aberrant MMR protein expression could be involved in progression of prostate cancer through PIN, early CaP to aggressive CaP. The loss of hPMS2 protein expression may serve as a marker for progression of CaP.


Subject(s)
Carcinogenicity Tests/methods , DNA Repair/genetics , Humans , India , Male , MutS Homolog 2 Protein/genetics , Mutation , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology
14.
Acta cir. bras ; 27(1): 18-22, Jan. 2012. ilus, tab
Article in English | LILACS | ID: lil-607991

ABSTRACT

PURPOSE: To develop experimental models to evaluate the effects of hydrochloric acid associated with the pepsin instilled in the mucosa of the upper esophagus and the esophagogastric junction of young male rats Wistar, simulating injury caused by gastroesophageal reflux on the mucosa of aero-digestive tract in humans as well as the action of the risk exposure of mucosa to cigarette smoke. METHODS: Fifty young male Wistar rats divided in 5 groups with 10 animals each one, respectively simulating pharyngo-laryngeal reflux and gastroesophageal reflux, pharyngo-laryngeal reflux and smoking, smoking only, gastroesophageal reflux and control group. RESULTS: The histopathologic studies no recorded neoplasias, only mild changes and no significant alterations. The hemo-oximetry (carboxyhemoglobin and methemoglobim) and CO2 concentration confirm that the animals were submitted to high intensity of exposure to carcinogens in tobacco and its derivatives. CONCLUSION: The experimental models were highly efficient, practical, easy to use and economical and can be employed in other similar studies to determine the harmful effects by smoking and reflux.


OBJETIVO: Desenvolver modelos experimentais para avaliar os efeitos do ácido clorídrico associado a pepsina, instilados na mucosa da parte superior do esôfago e da junção esofagogástrica de jovens ratos Wistar, simulando lesão causada por refluxo gastroesofágico na mucosa do trato aero-digestivo em humanos, bem como a ação da exposição ao risco de mucosa, como a fumaça de cigarro. MÉTODOS: Cinqüenta jovens ratos Wistar divididos em cinco grupos com 10 animais cada um, respectivamente, simulando o refluxo faringo-laríngeo e refluxo gastroesofágico, refluxo faringo-laríngeo e tabagismo, tabagismo só, refluxo gastroesofágico e grupo controle. RESULTADOS: os estudos histopatológicos não registraram neoplasias, apenas leves alterações e não significativas. O hemo-oximetria (carboxiemoglobina e metemoglobina) e concentração de CO2 corroboram que os animais foram submetidos a alta intensidade de exposição a substâncias cancerígenas do tabaco e seus derivados. CONCLUSÃO: os modelos experimentais desenvolvidos foram altamente eficientes, práticos, fáceis de usar e econômicos podendo ser empregados em outros estudos semelhantes para determinar os efeitos prejudiciais causados pelo tabagismo e refluxo.


Subject(s)
Animals , Male , Rats , Disease Models, Animal , Gastric Mucosa/drug effects , Gastroesophageal Reflux/complications , Gastrointestinal Agents/toxicity , Hydrochloric Acid/toxicity , Pepsin A/toxicity , Smoking/adverse effects , Carcinogenicity Tests , Carcinogens/toxicity , Gastric Mucosa/pathology , Gastroesophageal Reflux/chemically induced , Gastroesophageal Reflux/pathology , Random Allocation , Rats, Wistar , Smoking/physiopathology
15.
Article in Chinese | WPRIM | ID: wpr-246897

ABSTRACT

<p><b>OBJECTIVE</b>To discuss the tumorigenicity of immortalized endothelial cells differentiated from embryonic stem cells.</p><p><b>METHODS</b>The embryoid bodies (EB) formed in vitro from embryonic stem cells, were induced to differentiate into many "round cells" (the precursor of endothelial cells). These "round cells" later formed the vascular tube-like structures. To immortalize these cells, human telomerase reverse transcriptase (hTERT) cDNA was transfected into "round cells" by lipofectin, RT-PCR and immunocytochemistry were used to evaluate the immortalized cells. And the tumorigenicity of these cells were evaluated by being injected into nude mice subcutaneously.</p><p><b>RESULTS</b>95% of these transfected cells expressed Flk-1, CD34 and vWF, and could proliferate in large quantity in vitro (cell number was doubled in 2 days, and increased 12 times in 3 days), and were able to form tubular structures.</p><p><b>CONCLUSIONS</b>These results suggest that hTERT cDNA transfection can immortalize induced endothelial cells and tumorigenicity is found after immortalized cells are injected into nude mice subcutaneously.</p>


Subject(s)
Animals , Carcinogenicity Tests , Cell Differentiation , Cells, Cultured , Embryonic Stem Cells , Cell Biology , Endothelial Cells , Cell Biology , Endothelium, Vascular , Cell Biology , Mice , Mice, Inbred Strains , Mice, Nude , Telomerase , Genetics , Transfection
16.
Article in Chinese | WPRIM | ID: wpr-305035

ABSTRACT

<p><b>OBJECTIVE</b>To predict the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs) by cell transformation assay using BALB/c 3T3 cells and HPV16-E6E7-transfected BALB/c 3T3 cells (BALB/c-E6E7 cells).</p><p><b>METHODS</b>The cell transformation assays induced by PAHs using BALB-E6E7 cells and BALB/c 3T3 cells.</p><p><b>RESULTS</b>The initiating and promoting activities of PAHs examined in a BALB-E6E7 cell transformation assay were similar to in a BALB/c 3T3 cell transformation assay, which was up to the standard of agents classified by the IARC. There were much more transformed foci appeared and much shorter time consumed to accomplish phenotypic alterations in the BALB/c-E6E7 cell transformation assay than in the BALB/c 3T3 cell transformation assay. The BALB/c-E6E7 cell transformation assay was superior to the BALB/c 3T3 cell transformation assay in cost and labor performance, the sensitivity of transformation response.</p><p><b>CONCLUSION</b>The BALB/c-E6E7 cell transformation assay, with a satisfied prediction performance of initiating activity and promoting activity, would improve the overall process of safety and risk assessment of carcinogenicity.</p>


Subject(s)
Animals , BALB 3T3 Cells , Carcinogenicity Tests , Cell Transformation, Neoplastic , Mice , Mice, Inbred BALB C , Polycyclic Aromatic Hydrocarbons , Toxicity
17.
Arab Journal of Pharmaceutical Sciences. 2011; 4 (6): 47-58
in Arabic | IMEMR | ID: emr-110398

ABSTRACT

Carcinogenesis is a multistage process, involving oncogenes activation and tumor suppressor genes inactivation, as well as complex interactions between tumor and host tissues, leading ultimately to an invasive metastatic phenotype. p53 plays a critical role in tumor suppression mainly by inducing growth arrest, apoptosis, and senescence, as well as by blocking angiogenesis. In addition, p53 generally confers the cancer cell sensitivity to chemoradiation. Thus, p53 becomes the most appealing target for mechanism-driven anticancer therapy. For more than 30 years it has been known that cancer patients develop antibodies against p53. Many reports showed a very high frequency of p53 autoantibody positivity in the sera of patients with mamma carcinoma. This observation appointed the hopes of using p53 autoantibodies for diagnosis and prognosis. In addition there was a controversy whether p53 autoantibodies correlate with a good or bad prognosis. The reason for this controversy may be the use of different methods for the detection of p53 autoantibodies. Therefore, in this study, sera from mama carcinoma patients were initially tested by two different methods namely ELISA and Western Blot. In addition to the ELISA and Western Blot-analyses, we developed a filter binding epitopes, which are recognized by p53 autoantibodies. This assay allowed the mapping of the epitopes, which are recognized by p53 autoantibodies. The sequences of these epitopes might be useful for the treatment of tumor patients either by neutralizing p53 autoantibodies or for vaccination. Common epitopes are located in regions on the polypeptide chain of p53, which are functionally important for the role of p53 in growth control. Thus, the knowledge of these epitopes might be useful for the development of new strategies for cancer therapy


Subject(s)
Humans , Female , Carcinoma, Ductal, Breast , Breast Neoplasms , Autoantibodies , Carcinogenicity Tests , Oncogenes , Genes, Tumor Suppressor , Blotting, Western , Enzyme-Linked Immunosorbent Assay
18.
Iranian Journal of Public Health. 2011; 40 (4): 1-30
in English | IMEMR | ID: emr-122904

ABSTRACT

Many studies have shown that mycotoxin contamination of agricultural products is a challenge for individual's health especially in developing countries. Improper production and storage of foods, prepare conditions for aflatoxin production in crops, especially rice, wheat, pistachio, walnut, almond, etc which are the main sources of foods for people. Feeding livestock by contaminated bread is another way of human exposure to mycotoxins, especially aflatoxin and because of expensive methods for detecting and analyzing aflatoxin in laboratory; it is not measured in foods. This manuscript is a review of some Iranian and nonIranian reports about aflatoxin, its exposure ways, its adverse effect on human health and nutrition, as well as methods for reducing its exposure. Based on studies on foods, aflatoxin exposure is high in Iran. Since livestock feeding by contaminated bread is one of the potential ways for milk contamination, we should control and reduce aflatoxin contamination by improving production process, storage condition and livestock feeding as soon as possible. Pistachio is one of the most important exporting products of Iran and to maintain Iran's position in exporting of this product, specific regulations on lowering its contamination with aflatoxin should be considered seriously. Finally, effective controlling of all food and feedstuffs which are vulnerable to aflatoxin contamination is necessary to prevent its effects


Subject(s)
Carcinogenicity Tests , Mycotoxins , Livestock , Food Storage , Food Contamination , Oxidative Stress , Cytochrome P-450 Enzyme System , Congenital Abnormalities
19.
Article in Chinese | WPRIM | ID: wpr-332510

ABSTRACT

<p><b>OBJECTIVE</b>To study the acute toxicity of C25P polypeptide, a CCR5 antagonist, in mice and its carcinogenic effect in vitro.</p><p><b>METHODS</b>The acute toxicity of C25P polypeptide in mice was assessed by determining the maximum tolerated dose (MTD). The mice were given C25P at the dose of 3.64 g/kg by tail vein injection, and the control mice received saline (40 ml/kg) injection. The mice were continuously observed for 14 days after the administration and sacrificed on day 14 for routine blood test, examination of the blood biochemistry and pathological examination. The carcinogenicity of C25P polypeptide in vitro was evaluated in cultured cell lines by chromosome aberration test, cell transformation test and non-anchorage dependent growth test.</p><p><b>RESULTS</b>No mice died following administration of the drug, but 3 mice showed mild adverse reactions. The rats in both groups showed an increase in the body weight at a comparable rate. GPT increased and ALP decreased significantly in C25P polypeptide group (P<0.05). Most of the organs of the rats treated with in C25P polypeptide remained normal, but 3 mice showed pathologies in the lung, spleen and liver. Chromosome aberration test, cell transformation test and non-anchorage-dependent growth test all yielded negative results for C25P polypeptide.</p><p><b>CONCLUSION</b>C25P polypeptide is a low-toxicity drug that produces no apparent acute toxicity in mice or obvious carcinogenicity in vitro.</p>


Subject(s)
Animals , CCR5 Receptor Antagonists , Carcinogenicity Tests , Chemokines , Toxicity , Female , Male , Mice , Mice, Inbred Strains , Mutagenicity Tests , Peptides , Toxicity , Toxicity Tests, Acute
20.
Rev. bras. mastologia ; 20(2): 76-79, abr.-jun. 2010. ilus
Article in Portuguese | LILACS | ID: lil-605113

ABSTRACT

Objetivo: Testar um modelo experimental de indução de carcinogênese em raras Sprague-Dawley. Métodos: Foram estudadas 30 ratas fêmeas virgens Sprague-Dawley, induzidas ao carcinogênese mamário. Com 50 dias de vida, foi injectado 7,12-dimerilbenz(a)antrace no ventre por gavage. Com 12 semanas, as glândulas mamárias foram examinadas, assim como os tecidos cerebrais, pulmonares, ossos do fêmur e fígado. Resultados: Doze semanas após a injeção de DMBA, 85% das ratas apresentaram pelo menos um tumor mamário visível. Conclusão: O modelo experimental de carcinoma mamário induzido por DMBA mostrou-se efetivo e de fácil reprodução.


Objective: To test an experimental model of chemical mammary carcinogenesis induction in Sprague-Dawley rats. Methods: Thirty virgin Sprague-Dawley female rats, aged 50 days, received 20 mg of 7,12-dimethyLbenz(a)anthracene (DMBA) intragastrically by gavage. At 12 week their mammary glands were examined. Brain, Liver, bone and Lung tissue were also analyzed. Results: Twelve weeks after DMBA injection, 85% rats presented at Least one breast tumor. Conclusion: This experimental animal model of chemical mammary induced carcinogenesis is feasible and can be used in further experiments on the role of tumorigenic biomodulator substances.


Subject(s)
Animals , Female , Rats , /administration & dosage , Carcinogenicity Tests , Carcinoma/chemically induced , Disease Models, Animal , Breast Neoplasms/chemically induced , Rats, Sprague-Dawley
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