ABSTRACT
OBJETIVOS: Verificar se a presença de agentes infecciosos no conteúdo vaginal ou cervical pode alterar os resultados dos testes da proteína-1 fosforilada ligada ao fator de crescimento insulina-símile (phIGFBP-1) e das medidas do comprimento do colo uterino (CC) pela ultrassonografia transvaginal. MÉTODOS: Um total de 107 gestantes com antecedente de prematuridade espontânea foram submetidas ao teste da phIGFBP-1 e à realização da ultrassonografia transvaginal para medida do comprimento do colo uterino, a cada três semanas, entre 24 e 34 semanas. As infecções genitais foram pesquisadas imediatamente antes da realização dos testes. As pacientes foram distribuídas em quatro grupos (GA, GB, GC e GD) e dentro de cada grupo foi avaliada a correlação entre infecção genital e alteração nos testes utilizando a análise das razões de chance (OR) e o coeficiente de correlação de Pearson. RESULTADOS: Em cada grupo, mais de 50% das pacientes apresentaram infecção genital (GA 10/17; GB 28/42; GC 15/24; GD 35/53), sendo a vaginose bacteriana a principal alteração de flora vaginal. O resultado positivo para phIGFBP-1 (GA 10/10; GB 18/28; GC 15/15; GD 19/35) e CC≤20 mm (GA 10/10; GB 20/28; GC 10/15; GD 20/35) foram os resultados encontrados com maior frequência nas pacientes com infecção genital em todos os grupos. Porém, aplicando o coeficiente de correlação de Pearson foi identificada correlação entre infecção genital e positividade para os marcadores. CONCLUSÃO: A presença de alteração da flora vaginal e de outras infecções genitais não alteram significativamente os resultados do teste da phIGFBP-1 e da medida do colo uterino quando comparados aos casos sem infecção. No entanto, é necessária ...
PURPOSE: To determine if the presence of infectious agents in vaginal or cervical content can alter the results of the insulin-like growth factor binding protein-1 (phIGFBP-1) test and the measurement of cervical length (CC) by transvaginal ultrasonography. METHODS: A total of 107 pregnant women with a history of spontaneous preterm birth were submitted to the phIGFBP-1 test and to measurement of CC by transvaginal ultrasonography every 3 weeks, between 24 and 34 weeks of gestation. Genital infections were determined immediately before testing. The patients were distributed into four groups (GA, GB, GC, and GD) and the correlation between genital infection and changes in the tests was determined within each group based on the odds ratio (OR) and the Pearson correlation coefficient. RESULTS: In each group, over 50% of the patients had genital infections (GA 10/17; GB 28/42; GC 15/24; GD 35/53), with bacterial vaginosis being the main alteration of the vaginal flora. Positive results for phIGFBP-1(GA 10/10; GB 18/28; GC 15/15; GD 19/35) and CC≤20 mm (GA 10/10; GB 20/28; GC 10/15; GD 20/35) were obtained more frequently in patients with genital infection in all groups. Nonetheless, when applying the Pearson correlation coefficient we detected a poor correlation between genital infection and positivity for markers. CONCLUSION: The presence of changes in the vaginal flora and of other genital infections does not significantly alter the results of phIGFBP-1 and the measurement of cervical length when compared to cases without infection. However, more studies with larger samples are necessary to confirm these results. .
Subject(s)
Humans , Antimetabolites, Antineoplastic/pharmacology , Erythroid Precursor Cells/cytology , Phenylacetates/pharmacology , Transcription Factors/metabolism , Antigens, Surface/metabolism , Cell Line , Cell Differentiation/drug effects , DNA-Binding Proteins/metabolism , Erythroid-Specific DNA-Binding Factors , Erythroid Precursor Cells/drug effects , Flow Cytometry , GATA1 Transcription Factor , Globins/metabolism , RNA, Messenger/metabolism , Tumor Cells, CulturedABSTRACT
Objetivo. Analizar la percepción que el prestador de servicios de salud y el adulto mayor (AM) tienen sobre el maltrato al AM en los servicios públicos de salud, en ciudades seleccionadas de México. Material y métodos. De 2009 a 2012 se realizó un estudio con diseño cualitativo y estrategia de triangulación de fuentes de datos; se efectuaron entrevistas semiestructuradas a 13 prestadores y a 12 ancianos para recuperar su experiencia en el tema. El análisis utilizó procedimientos de la Teoría Fundamentada. Resultados. El maltrato contra el AM es una práctica naturalizada por el personal y por el anciano, la cual se manifiesta de formas diversas. Conclusiones. La institucionalización, profesionalización histórica y falta de conciencia sobre las necesidades de los AM demandan cambios de planeación, organización y supervisión del Sistema de Salud. El personal requiere intervenciones de formación, capacitación y cambio de actitudes/comportamiento, para otorgar atención integral, digna, humana y de respeto a los Derechos Humanos de los AM.
Objective. To analyze the health care providers (HCP) and elderly patients' perceptions about abuse of the elderly by health personnel of public health services, in selected cities in Mexico. Materials and methods. A qualitative study and a strategy of data triangulation were performed during 2009 and 2012; 13 HCPs and 12 elders were interviewed, in order to obtain their experience regarding elder abuse. Grounded Theory proceedings were used for the analysis. Results. Elder abuse is a naturalized practice, from HCP and elderly people's point of view; these perceptions are showed in different ways. Conclusion. Institutionalization, historical professionalization and lack of consciousness about needs of the elderly (sociocultural and economic), require changes in planning, organization and monitoring process in the Health System; training and educational interventions on staff and exchange attitudes and behavior are necessary in order to offer a health care that is comprehensive, decent, human and with respect for the human rights.
Subject(s)
Animals , Female , Humans , Mice , Antimetabolites, Antineoplastic/pharmacology , Cyclins/metabolism , Enzyme Inhibitors/metabolism , Phenylacetates/pharmacology , Antisense Elements (Genetics) , Breast Neoplasms , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cell Division/drug effects , Cyclin-Dependent Kinases/genetics , Cyclin-Dependent Kinases/metabolism , Cyclins/genetics , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/enzymology , Gene Expression Regulation, Neoplastic/physiology , Mice, Knockout , Phosphorylation , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/metabolism , Retinoblastoma Protein/metabolism , Signal Transduction/physiology , Tumor Cells, Cultured/cytology , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/enzymology , Up-Regulation/drug effectsABSTRACT
Introdução: A nefrolitíase é uma patologia frequente, com alta taxa de prevalência e recorrência, ocorrendo por processo multifatorial e complexo. Objetivo: Analisar as principais características dietéticas e metabólicas de pacientes com nefrolitíase e compará-los com grupo controle. Métodos: Estudo observacional, transversal, com 31 pacientes com nefrolitíase (NE) e 18 saudáveis. Na ingestão dietética, foram verificados sódio, cálcio, proteína, potássio, vitamina C, oxalato e a ingestão hídrica em ambos os grupos. Na avaliação metabólica, foi analisada excreção urinária de citrato e oxalato. Também foi avaliada presença de hipertensão arterial e Índice de Massa Corporal (IMC). Resultados: Quanto ao grupo NE, verificou-se que 45,2% apresentou alta ingestão de sódio e 100% de oxalato. Foi também observada baixa ingestão de cálcio em 93,5%, potássio em 100% e vitamina C em 94,9%. Com relação à proteína, apenas 12,5% apresentou ingestão normoproteica. Quanto à ingestão hídrica, 12,9% apresentou ingestão menor que 1 litro, 54,8% entre 1 a 2 litros, e 32,3% maior que 2 litros. Foi observada hipertensão arterial sistêmica em 64,5% desses pacientes e excreção adequada de citrato e oxalato em 90,5% deles. Não foi verificada diferença estatística significativa na ingestão alimentar, IMC, e excreção de oxalato entre os grupos. No entanto, o grupo NE apresentou maior excreção de citrato. Conclusão: Verificou-se nos dois grupos elevada prevalência de pacientes com sobrepeso, alta ingestão de oxalato e sódio, além de inadequação nas ingestões de cálcio, potássio e vitamina C. No grupo NE, foi observada ...
Introduction: Nephrolithiasis is a common condition with high prevalence and recurrence, occuring by a complex and multifactorial process. Objective: To analyze the main dietary and metabolic characteristics of patients with nephrolithiasis and compare them with a control group. Methods: A crosssectional study with 31 patients with nephrolithiasis (NE) and 18 healthy. By the dietary intake it were observed sodium, calcium, protein, potassium, vitamin C, oxalate and water intake in both groups. Metabolic assessment were analyzed in urinary excretion of oxalate and citrate. The presence of hypertension and body mass index (BMI) was also evaluated. Results: In the NE group, it was found that 45.2% had a high intake of sodium and 100% a high intake of oxalate. It was also observed a low calcium, potassium and vitamin C intake by 93.5%, 100% and 94.9% respectively. Regarding protein, only 12.5% had normal protein intake. Concerning water intake, 12.9% had an ingestion less than 1 liter, 54.8% between 1 and 2 liters and 32.3% higher than 2 liters. Hypertension was observed in 64.5% of patients and adequate excretion of oxalate and citrate in 90.5% of them. There was no statistically difference in food intake, BMI and oxalate excretion between groups. However, the NE group showed higher urinary citrate. Conclusion: It was found in both groups a high prevalence of overweight patients, a high intake of oxalate and sodium, in addition to inadequate intakes of calcium, potassium and vitamin C. The NE group showed high protein intake and increased excretion of citrate. .
Subject(s)
Animals , Rats , Antimetabolites, Antineoplastic/pharmacology , Genes, Homeobox/genetics , Glioma/genetics , Phenylacetates/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Glioma/pathology , RNA, Messenger/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tumor Cells, Cultured , Up-Regulation/drug effectsABSTRACT
The survival of infective larvae (L3) of Trichostrongylus colubriformis was evaluated on Brachiaria, Coast-cross and Aruana forage grasses. Feces of sheep parasitized exclusively by T. colubriformis were deposited in winter and spring on experimental plots whose grasses were cut at two heights: 5 cm and 30 cm. One, two, four, eight, 12 and 16 weeks after depositing the feces, fecal and forage samples were collected for the retrieval and quantification of L3. Retrieval of L3 from feces and forage was negligible in winter due to the dry weather, although a few larvae were retrieved in the last larval collections. However, L3 retrieval from fecal samples was greater in spring, especially two weeks after feces were deposited on 30 cm high grasses. At this time, the L3 retrieval rate from the three forage grasses differed significantly (P <0.05), with Aruana grass showing the highest average L3 retrieval rate, followed by Coast-cross and Brachiaria. In conclusion, the winter drought proved very unfavorable for the presence of L3 in the environment, and the microclimate of Aruana pastureland was generally the most favorable for the retrieval of infective larvae.
A sobrevivência de larvas infectantes (L3) de Trichostrongylus colubriformis foi avaliada em pastagem de Braquiária, Coast-cross e Aruana. Fezes de ovinos parasitados exclusivamente por T. colubriformis foram depositadas no inverno e na primavera em parcelas experimentais com duas alturas de corte da forragem, 5 cm e 30 cm. Uma, duas, quatro, oito, 12 e 16 semanas após o depósito, amostras de fezes e de forragem foram coletadas para a recuperação e quantificação de L3. Devido à seca no inverno, a recuperação de L3 das fezes e da forragem foi ínfima, embora tenha havido recuperação de algumas larvas nas últimas coletas. Por outro lado, na primavera houve maior recuperação de L3 das amostras, especialmente duas semanas após a deposição das fezes em meio às pastagens com 30 cm de altura. Nesse momento, houve diferença significativa (P<0,05) entre as três forrageiras, com maior média de L3 no capim Aruana, seguido de Coast-cross e Braquiária. Em conclusão, a seca registrada no período de inverno se mostrou bastante desfavorável à presença de L3 no ambiente e, de forma geral, o microclima da pastagem de Aruana foi o que mais favoreceu a recuperação de larvas infectantes.
Subject(s)
Humans , Antimetabolites, Antineoplastic/pharmacology , Carcinoma, Renal Cell/enzymology , Floxuridine/pharmacology , Fluorouracil/pharmacology , Kidney Neoplasms/enzymology , Thymidine Phosphorylase/metabolism , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Kidney/enzymology , Reference ValuesABSTRACT
O artigo analisa o livro Boys in white: student culture in medical school, de Howard S. Becker, Blanche Geer, Everett C. Hughes e Anselm Strauss, considerado um dos modelos de pesquisa qualitativa em sociologia. A análise aborda as trajetórias dos autores, do livro, da pesquisa qualitativa e dos estudantes de medicina, enfatizando sua importância nas origens da sociologia médica e da sociologia da educação médica. Na trajetória dos autores são apresentados aspectos biobibliográficos; na da pesquisa qualitativa, o modo como essa metodologia de investigação atravessa a construção do trabalho de campo; e na dos estudantes, sua forma de atravessar os primeiros anos da escola médica e construir sua própria “cultura do estudante”.
This article analyzes Boys in white: student culture in medical schoolby Howard S. Becker, Blanche Geer, Everett C. Hughes and Anselm Strauss, considered a model of qualitative research in sociology. The analysis investigates the trajectories of the authors, the book, qualitative analysis, and the medical students, emphasizing their importance in the origins of medical sociology and the sociology of medical education. In the trajectory of the authors, bibliographical information is given. The trajectory of qualitative research focuses on how this methodology influences the construction of the field. The investigation of the students’ trajectory shows how they progress through their first years at medical school to build their own student culture.
Subject(s)
Animals , Female , Mice , Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/pharmacology , Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Estrogens , Estrogen Antagonists/pharmacology , Growth Inhibitors/pharmacology , Neoplasms, Hormone-Dependent/drug therapy , Phenylacetates/pharmacology , /biosynthesis , Tamoxifen/pharmacology , Adenocarcinoma/pathology , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/pathology , Cell Differentiation/drug effects , Cell Division/drug effects , Drug Synergism , Genes, ras , Mice, Nude , Neoplasm Transplantation , Neoplasms, Hormone-Dependent/pathology , /physiology , Phenylacetates/administration & dosage , /genetics , Transfection , Tamoxifen/administration & dosage , Tumor Cells, Cultured/drug effectsABSTRACT
El metotrexate (MTX) es uno de los medicamentos frecuentemente utilizados en el cáncer infantil señalándose además, como agente citotóxico de la mucosa bucal, que puede desencadenar el proceso inflamatorio e incremento de la vascularidad en los tejidos epiteliales durante las fases iniciales de la mucositis oral. El presente trabajo tiene como objetivo determinar la producción de citocinas proinflamatorias IL-1b, IL-6 y TNF-a en cultivos de células epiteliales tratadas con MTX. Se realizaron cultivos de células epiteliales de laringe humana obtenidas de la línea celular Hep-2, con diferentes dosis de MTX en distintos tiempos de incubación, y a su vez se analizó la citotoxicidad del fármaco mediante el ensayo colorimétrico, el cual se basa en la reducción metabólica del bromuro de 3-(4,5- dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT), y la producción de citocinas proinflamatorias mediante el ensayo inmuno enzimático indirecto (ELISA). En cuanto a los resultados se observó, que los cultivos de células Hep-2 presentaron aumento en la producción de las citocinas proinflamatorias a las 72 horas al utilizar las dosis de 0.32µM MTX. Estos resultados sugieren que la dosis y el tiempo de exposición del MTX alteran la fisiología de las células epiteliales humanas, lo cual podrían desempeñar un papel importante durante las fases de iniciación y de desarrollo de la mucositis oral.
Methotrexate (MTX), a drug commonly used in childhood cancer, has also been indicated as a cytotoxic agent of the oral mucosa, which can trigger the inflammatory process and increase the vascularity of epithelial tissues during the early stages of oral mucositis. The aim of this study was to determine the production of proinflammatory cytokines IL-1b, IL-6 y TNF-a in epithelial cell cultures treated with MTX. Epithelial cells of human larynx, obtained from the cell line Hep-2, were cultured with different doses of MTX during different incubation times. The drug cytotoxicity was analyzed by means of the colorimetric test, which is based on the metabolic reduction of the bromide of 3-(4, 5-dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT); and the proinflammatory cytokines production by the test enzyme-linked immunosorbent assay (ELISA). Cultures of HEp-2 cells showed increased production of proinflammatory cytokines at 72 hours with 0.32µM of MTX. These results suggest that depending on the dose and exposure time, MTX alters the physiology of human epithelial cells, which may play an important role during the phases of initiation and development of oral mucositis.
Subject(s)
Humans , Antimetabolites, Antineoplastic/pharmacology , Epithelial Cells/drug effects , Interleukin-1beta/biosynthesis , /biosynthesis , Methotrexate/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Antimetabolites, Antineoplastic/adverse effects , Cell Line, Tumor , Cell Survival , Carcinoma/pathology , Enzyme-Linked Immunosorbent Assay , Epithelial Cells/metabolism , Inflammation , Interleukin-1beta/genetics , /genetics , Laryngeal Neoplasms/pathology , Methotrexate/adverse effects , Stomatitis/chemically induced , Tetrazolium Salts , Thiazoles , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.
Subject(s)
Humans , Adenine Nucleotides/pharmacology , Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Arabinonucleosides/pharmacology , Caspase 3/metabolism , Caspase 7/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , G2 Phase Cell Cycle Checkpoints/drug effects , Gene Knockdown Techniques , Leupeptins/pharmacology , Lung Neoplasms/metabolism , M Phase Cell Cycle Checkpoints/drug effects , Mesothelioma/metabolism , Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Stilbenes/pharmacology , bcl-X Protein/antagonists & inhibitorsABSTRACT
PURPOSE: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. MATERIALS AND METHODS: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. RESULTS: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. CONCLUSION: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/pharmacology , Glutamates/pharmacology , Guanine/analogs & derivatives , Lung Neoplasms/drug therapy , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Pharmacogenetics , Phosphoribosylglycinamide Formyltransferase/genetics , Polymorphism, Single Nucleotide , Tetrahydrofolate Dehydrogenase/genetics , Thymidylate Synthase/geneticsABSTRACT
BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMN) are precursor lesions of fatal pancreatic cancer. Physiological function of microRNA is to regulate the stability and translation of mRNA. The aberrant microRNA expression is commonly observed in many cancers. The aim of this study was to analyze the expression pattern of microRNA in IPMN and evaluate the role of the microRNA. METHODS: Using two paraffin-embedded IPMN tissues, microRNA expression of normal tissue, IPMN adenoma and carcinoma were compared by cDNA-mediated annealing, selection, extension and ligation microarray assay. Using real time PCR, expression levels of aberrantly up-regulated microRNAs were assessed in another 20 IPMNs, four pancreatic cancer cell lines (Panc1, MiaPaCa-2, XPA-3, BxPC-3) and immortalized pancreatic ductal cell line (HPNE). Effect of suppressing highly over-expressed two microRNAs in pancreatic cancer cell lines with anti-microRNA inhibitors were evaluated using CCK-8 assay. RESULTS: Among aberrantly expressed 122 microRNAs in IPMN, miR-552, miR-25*, miR-183, miR-1300, miR-196a, miR-182*, and miR-30c-1* were consistently increased more than 3-fold. On average, miR-196a and miR-183 increased 10,824 folds and 26,519 folds in four pancreatic cancer cell lines compared with HPNE. These two microRNAs were also over-expressed in 20 IPMNs compared with HPNE. After applying anti-miRNA inhibitors, cell survival of four pancreatic cancer cell lines decreased by 24.5% with anti-miR-196a and by 14.2% with anti-miR-183 on average. CONCLUSIONS: Aberrant expression of 122 microRNAs was observed in IPMN. Two microRNAs, miR-196a and miR-183-increased in IPMN and pancreatic cancer cell lines compared with immortalized dancreatic ductal cell line. The inhibitions of these microRNAs repressed cell proliferation of pancreatic cancer cell lines.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma, Mucinous/diagnosis , Adenoma/diagnosis , Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Carcinoma, Papillary/diagnosis , Cell Line , Deoxycytidine/analogs & derivatives , MicroRNAs/antagonists & inhibitors , Pancreatic Neoplasms/diagnosis , Real-Time Polymerase Chain Reaction , Up-RegulationABSTRACT
PURPOSE: Hypoxia-inducible factor-1alpha (HIF-1alpha) primarily mediates the hypoxic response. HIF-1alpha induction by various stimuli contributes to cell proliferation and survival. To investigate the effect of HIF-1alpha, we used small interfering RNA (siRNA), and expected that cell apoptosis and sensitivity to chemotherapeutic drug increase, when we blocked the HIF-1alpha gene. Thus we performed in vitro and in vivo experiment to clarify the effect of hypoxia-inducible factor-1alpha on tumor growth. MATERIALS AND METHODS: We made control and HIF-1alpha siRNA using vector plasmid and then transfected Mia-paca cell lines with these RNAs. After selection with geneticin, two new cell lines were made, confirmed via immunoblotting. After treating with gemcitabine, each cell line was assayed to confirm the effect of HIF-1alpha siRNA using the cell proliferation assay and capase-3 assay. And then in vivo study was performed using female athymic nude mice. After subcutaneously injecting each new cell lines, intraperitoneal gemicitabine chemotherapy was performed for 3 weeks. During that period, we analyzed the difference of tumor growth rate. RESULTS: The tumor growth of HIF-1alpha siRNA-transfected group was slower than that of the control group both in vitro and in vivo experiment. CONCLUSION: The suppression of HIF-1alpha results in decrease of cell proliferation and increase of chemosensitivity of pancreatic cancer cell line. Therefore, targeting the HIF-1alpha may be useful treatment modality for some pancreatic cancers.
Subject(s)
Animals , Female , Humans , Mice , Antimetabolites, Antineoplastic/pharmacology , Blotting, Western , Caspase 3/metabolism , Cell Hypoxia , Cell Line, Tumor , Cell Proliferation , Cell Survival/drug effects , Deoxycytidine/analogs & derivatives , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , RNA Interference , RNA, Small Interfering/genetics , Random Allocation , TransfectionABSTRACT
CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s) will achieve the maximum clinical response. AIMS: To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA) and correlated them to the clinical response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS: Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to combination of cisplatin and methotrexate and 36 (69%) to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03) between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of chemo-response of oral cancer.
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Antineoplastic Agents/pharmacology , Biological Assay , Carcinoma, Squamous Cell/drug therapy , Cisplatin/pharmacology , Female , Fluorouracil/pharmacology , Humans , Male , Methotrexate/pharmacology , Middle Aged , Mouth Neoplasms/drug therapy , Prospective Studies , Treatment OutcomeABSTRACT
OBJETIVO: Avaliar a atividade proliferativa dos fibroblastos da cápsula de Tenon normal, proveniente de portadores de pterígios primários e recidivados. MÉTODOS: Foi realizado estudo prospectivo, aleatório, avaliando-se fragmentos da cápsula de Tenon normal, removidos de 20 portadores de pterígios primários e 21, recidivados. A taxa de proliferação foi avaliada em fibroblastos de terceira passagem, quando as culturas foram expostas a agentes antimitóticos: mitomicina C e 5-fluorouracil. Os dados obtidos foram submetidos à análise estatística. RESULTADOS: Dentre os 41 espécimes cultivados, apenas 1 de pterígio primário e 2 de recidivado proliferaram. Quando expostos a mitomicina C e ao 5-fluorouracil não houve diferença estatisticamente significativa quanto a inibição de proliferação celular. CONCLUSÃO: Desta forma, in vitro, ambos os antimitóticos estudados têm a mesma eficácia na inibição da proliferação sobre os fibroblastos de cápsulas de Tenon normal.
PURPOSE: To evaluate the fibroblast proliferation activity of normal Tenon's capsule from primary and recurrent patients with pterygium. METHODS: A randomized prospective study was performed with 41 normal Tenon's capsule fragments from 21 primary and 20 recurrent patients with pterygium. The sample was collected from the inferior cul-de-sac. Proliferation rate from fibroblasts were evaluated after mitomycin C and 5-fluorouracil exposition. Data were submitted to statistical analysis. RESULTS: Of the 41 cultivated normal Tenon's capsules, only 1 from primary and 2 from recurrent pterygium patients proliferated. After antimitotic exposition, the proliferation rate was similar with both drugs. CONCLUSION: Mitomycin and 5-fluorouracil promote similar inhibition regarding proliferation of normal Tenon's fibroblast cultures.
Subject(s)
Humans , Antimetabolites, Antineoplastic/pharmacology , Cell Proliferation/drug effects , Fibroblasts/drug effects , Fluorouracil/pharmacology , Mitomycin/pharmacology , Pterygium/pathology , Cell Count , Cell Culture Techniques , Prospective Studies , RecurrenceABSTRACT
Rotula aquatica was extensively used by vaidyas (Ayurvedic practioners) in holistic treatment of cancer. In the present study, an attempt has been made to evaluate the antimitotic activity of R. aquatica. Preliminary antimitotic screening was done using Allium cepa root tip assay. The mitotic index of the root tips markedly decreased with increasing concentration of the aqueous extract. The different fractions obtained by successive extraction of R. aquatica using solvents of increasing polarity were also evaluated for their antimitotic activity. Tannins were isolated which showed a better activity than the non-tannin fraction. Experiments were also carried out with incorporation of folic acid in the aqueous extract. Folic acid inhibited the antimitotic activity of aqueous extract of R. aquatica in a dose dependent manner. The results obtained were compared with methotrexate--a known drug available in market as anti-cancer agent. The studies were extended to human cells using 3 pancreatic cancer cell lines, viz: HPAF-II, BxPC-3, and CAPAN-2. Extract of R. aquatica was found to be extremely effective in the prevention of cell proliferation of the pancreatic cancer cell lines. The phytochemical evaluation revealed presence of polyphenols (tannins) and steroids. A HPTLC fingerprinting was developed and studied. Two compounds were isolated and subjected to spectral studies like UV, IR and mass spectrums. The empirical formula was derived by considering this data with elemental analysis of the compounds.
Subject(s)
Allium/chemistry , Antimetabolites, Antineoplastic/pharmacology , Boraginaceae/chemistry , Cell Division/drug effects , Chromatography, High Pressure Liquid , Folic Acid/pharmacology , Mass Spectrometry , Methotrexate/pharmacology , Mitotic Index , Pancreatic Neoplasms/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Plant Roots/cytology , Steroids/chemistry , Tannins/metabolismABSTRACT
The telomerase is a ribonucleoprotein enzyme to which multiple functions have been attributed, the most important of these is the maintenance of the telomere which is related with cellular immortalization and cancer. 85 of human tumors have telomerase activity, that in normal cells goes undetected. These characteristics make the telomerase an attractive target for chemotherapy.
Subject(s)
Humans , Azacitidine , Telomerase , Neoplasms , Neoplasm Proteins/physiology , Azacitidine , Tumor Cells, Cultured , Drug Design , Cellular Senescence , Telomerase , Neoplasms , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/therapeutic use , Drug Screening Assays, Antitumor , Enzyme Induction , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Biomarkers, Tumor , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/chemistry , Neoplasm Proteins/genetics , Gene Expression Regulation, Neoplastic , Telomere/metabolism , Genetic TherapyABSTRACT
Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15 percent of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Colorectal Neoplasms/drug therapy , Organoplatinum Compounds/therapeutic use , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents, Phytogenic/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Camptothecin/metabolism , Camptothecin/pharmacology , Clinical Trials as Topic , Drug Therapy, Combination , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Leucovorin/pharmacology , Leucovorin/therapeutic use , Organoplatinum Compounds/metabolism , Organoplatinum Compounds/pharmacologyABSTRACT
Gemcitabina es un agente activo en el tratamiento del cáncer de pulmón (CPCNP). El tratamiento semanal con gemcitabina, como agente único, ha mostrado respuestas del 20 al 26 por ciento. Este estudio fase 2 fue realizado para determinar la eficacia y seguridad de gemcitabina 1000 mg/m2, administrado semanalmente. Por tres semanas, seguido de una de descanso (ciclos de 28 días): los pacientes requirieron tener evidencia histológica de CPCNP y enfermedad avanzada; estado de desempeño de Zubrod de 0 a 2 y enfermedad medible. No se permitió que hubieran recibido tratamiento previo. Veinte pacientes, diez hombres y diez mujeres con una edad promedio de 60 años fueron incluidos en el estudio. La mayor parte de los pacientes (doce pacientes, 60 por ciento) tuvieron EC IIIb y, diagnóstico de adenocarcinoma (trece pacientes, 65 por ciento). Cuatro pacientes (20 por ciento) tuvieron EC IIIa y otros cuatro (20 por ciento) tuvieron EC IV, siete pacientes (35 por ciento) tuvieron variedad histológica epidermoide. Los pacientes recibieron un total de 62 ciclos y un promedio de 3.1 ciclos de terapia con gemcitabina. De los dieciocho pacientes que se incluyeron para evaluar eficacia, en seis se obtuvo respuesta parcial con un porcentaje de respuesta del 33.3 por ciento. La supervivencia media fue de siete meses (dos a 15 meses) con un tiempo medio libre de enfermedad de 3.5 m (1-15 meses) y un año de supervivencia del 22.2 por ciento. Toxicidad hematológica grado 3 y 4 de la Organización Mundial de la Salud (OMS) fue observada en menos del 2 por ciento de todos los ciclos. La toxicidad más común grado 3 y 4 no hematológica fue náusea y vómito observada en menos del 5 por ciento de los ciclos. Elevación transitoria de transaminasas se observó en menos del 4 por ciento de los ciclos. Un paciente presentó hepatitis fulminante y rash generalizado que, a consideración de los investigadores, se debió a una reacción de hipersensibilidad por toxicidad de la gemcitabina. En conclusión, gemcitabina como agente único en administración semanal de 1000 mg/m2 es segura y efectiva en el tratamiento del CPCNP avanzado.
Subject(s)
Humans , Male , Female , Middle Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/pharmacologyABSTRACT
Amphibian gastrulation was used as a model system to study the action of the nucleoside 1-beta-D-arabinofuranosylcytosine (Ara-C) on the early events of amphibian morphogenesis. Ara-C inhibits both glycoprotein and glycolipid synthesis and interferes with DNA synthesis. Thus, it is useful to investigate the importance of the cell surface and the nucleous during Bufo arenarum morphogenesis. Living embryos were incubated with Ara-C at blastula and gastrula stages. Treated-embryos undergo abnormal gastrulation, most of the embryos exogastrulate, although some do not gastrulate at all. This antimetabolite did not interfere with neural induction, as partial exogastrulae developed a small neural tube. We have proven that Area-C disturbs the typical intercellular organization and inhibits the radial intercalation of the blastocoelic roof. The mesodermal migration is the most affected morphogenetic process. The results described in this paper demonstrate that the timing of gastrulation movements strongly involves the participation of surface and extracellular molecules in cell recognition and cell interaction but does not involve a significant increase in cell division rate and can also occur in the absence of the cell division.