摘要
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摘要
PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.
Subject(s)
Animals , Female , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/metabolism , Cadherins , Cell Line, Tumor , Cell Movement , Cell Proliferation/drug effects , Cytokines , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Diterpenes/pharmacology , Diterpenes/therapeutic use , Epithelial-Mesenchymal Transition/drug effects , Mice, Nude , Neoplasm Invasiveness , Pancreatic Neoplasms/diet therapy , Pancreatic Neoplasms/pathology , Real-Time Polymerase Chain Reaction , Signal Transduction/drug effects , Vimentin/metabolism摘要
This study aimed to investigate the feasibility of the establishment of a human cancer xenograft model using samples from computed tomography (CT)-guided percutaneous biopsy. Fresh tumor tissues obtained from 10 cancer patients by CT-guided percutaneous biopsy were subcutaneously inoculated into NOD-Prkdcem26Il2rgem26Nju (NCG) mice to establish human patient-derived tumor xenograft (PDTX) models. The formation of first and second generation xenografts was observed, and tumor volume was recorded over time. Tumor tissue consistency between the PDTX model and primary tumors in patients was compared using H&E staining and immunohistochemistry. Pharmacodynamic tests of clinically used chemotherapeutic drugs were conducted on second generation xenografts, and their effects on tumor growth and body weight were observed. CT-guided percutaneous biopsy samples were successfully collected from 10 patients with advanced cancers. The PDTX model was established in mice using tumor samples obtained from 4 cancer patients, including one small cell carcinoma sample, two adenocarcinoma samples, and one squamous cell carcinoma sample. The success rate was 40%. The obtained PDTX model maintained a degree of differentiation, and morphological and structural characteristics were similar to primary tumors. The pharmacodynamic test of chemotherapeutic drugs in the PDTX model revealed a therapeutic effect on tumor growth, as expected. CT-guided percutaneous biopsy samples can be effectively used to establish a PDTX model, and test these chemotherapy regimens.
Subject(s)
Humans , Animals , Male , Female , Middle Aged , Aged , Adenocarcinoma/pathology , Disease Models, Animal , Liver Neoplasms/pathology , Lung Neoplasms/pathology , Xenograft Model Antitumor Assays/methods , Antineoplastic Agents/pharmacokinetics , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacokinetics , Feasibility Studies , Image-Guided Biopsy/methods , Mice, Inbred Strains , Organoplatinum Compounds/pharmacokinetics , Tomography, X-Ray Computed , Xenograft Model Antitumor Assays/instrumentation摘要
Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.
Subject(s)
Humans , Pancreatic Neoplasms/therapy , Adenocarcinoma/therapy , Practice Guidelines as Topic , Disease Management , Consensus Development Conferences as Topic , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Chemoradiotherapy , Latin America , Antimetabolites, Antineoplastic/therapeutic use摘要
Resumo A gencitabina é um fármaco utilizado no tratamento de vários tipos de neoplasias malignas. Há poucas descrições de associação entre a droga e a síndrome hemolítico-urêmica (SHU), apesar de os pacientes em questão terem ido a óbito em pelo menos 50% dos casos. O presente artigo relata o caso de uma paciente com 25 anos de idade em remissão diagnosticada com colangiocarcinoma que apresentou anemia hemolítica microangiopática acompanhada de insuficiência renal aguda anúrica após cinco ciclos de quimioterapia com gencitabina; as manifestações eram condizentes com SHU causada pelos efeitos colaterais do medicamento. A administração de gencitabina foi interrompida, e a paciente foi tratada com hemodiálise, transfusões de sangue, trocas de plasma, corticosteroides, doxiciclina e rituximabe. Foi atingido um desfecho favorável; mais especificamente, a hemólise foi controlada e a função renal foi plenamente restabelecida.
Abstract Gemcitabine is a medication used to treat various types of malignant neoplasms. Its association with hemolytic uremic syndrome (HUS) has been described in few cases, although these cases have resulted in mortality rates of at least 50%. We report on the case of a 25-year-old patient with cholangiocarcinoma in remission who developed microangiopathic hemolytic anemia with acute anuric renal failure after receiving 5 cycles of gemcitabine chemotherapy; this condition was consistent with HUS caused by the side effects of this drug. The administration of gemcitabine was stopped, and hemodialysis, blood transfusions, plasma exchanges, steroids, doxycycline, and rituximab were used to treat the patient. A favorable outcome was achieved; in particular, hemolysis was controlled, and renal function was completely recovered.
Subject(s)
Humans , Female , Adult , Deoxycytidine/analogs & derivatives , Hemolytic-Uremic Syndrome/chemically induced , Antimetabolites, Antineoplastic/adverse effects , Bile Duct Neoplasms/drug therapy , Cholangiocarcinoma/drug therapy , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use摘要
Para fundamentar as ações de cuidado integralizado em saúde da mulher é necessário compreender de que modo o apoio social pode contribuir para minimizar as repercussões do diagnóstico e do tratamento da neoplasia mamária. O objetivo deste estudo é analisar a contribuição da produção científica nacional e internacional acerca do apoio social percebido por mulheres diagnosticadas com câncer de mama. A amostra foi constituída de 12 publicações, obtidas a partir de critérios de inclusão preestabelecidos, nas bases de dados MedLine, Lilacs e PsycINFO, na última década (2000-2010). Os resultados foram sistematizados em categorias temáticas: percepção do apoio familiar, apoio social percebido, percepção do apoio educacional, necessidade de aprimoramento da pesquisa e assistência às mastectomizadas e suas famílias. Os estudos dedicados à dimensão subjetiva do apoio social ainda são incipientes. As evidências disponíveis sugerem que a literatura é circunscrita a temas de interesse das profissões tradicionais da área da saúde, como Enfermagem e Medicina, privilegiando construtos que podem ser diretamente quantificados. A preocupação com o apoio social deve estar presente desde a fase de diagnóstico até a reabilitação psicossocial, como parte do processo de enfrentamento.
It is necessary to understand how social support can contribute to minimize the impact of the diagnosis and treatment of mammary tumors in order to underpin the actions of comprehensive women's health care. This study seeks to analyze the contribution of the national and international literature regarding the perceived social support by women diagnosed with breast cancer. Twelve studies were selected from the MedLine, Lilacs and PsycINFO databases over a 10-year period (2000-2010) with pre-defined criteria for inclusion. The results were organized into thematic categories: the perception of family support; perceived social support; the perception of educational support; the need to improve the research and the assistance given to women after mastectomy and their families. The studies dedicated to the subjective dimension of social support are still incipient. The available evidence suggests that the literature is limited to topics of interest to the traditional health professions, such as Nursing and Medicine, focusing on constructs that can be directly quantified. The concern with social support must be present from the time of diagnosis to psychosocial rehabilitation, as part of the process of tackling the situation.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Antimetabolites, Antineoplastic/blood , Antimetabolites, Antineoplastic/pharmacokinetics , Colorectal Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Age Factors , Antimetabolites, Antineoplastic/therapeutic use , Area Under Curve , Capecitabine , Colorectal Neoplasms/metabolism , Deoxycytidine/blood , Deoxycytidine/pharmacokinetics , Deoxycytidine/therapeutic use , Floxuridine/blood , Fluorouracil/blood , Fluorouracil/pharmacokinetics , Fluorouracil/therapeutic use , Glomerular Filtration Rate , Metabolic Clearance Rate , Sex Factors摘要
This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antimetabolites, Antineoplastic/administration & dosage , Bile Ducts, Intrahepatic , Bile Duct Neoplasms/drug therapy , Cholangiocarcinoma/drug therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Embolization, Therapeutic , Antimetabolites, Antineoplastic/adverse effects , Combined Modality Therapy , Deoxycytidine/adverse effects , Quality of Life , Treatment Outcome摘要
Objective. A retrospective evaluation of waiting times for elective procedures was conducted in a sample of Mexican public hospitals from the following institutions: the Mexican Institute for Social Security (IMSS), the Institute for Social Security and Social Services for Civil Servants (ISSSTE) and the Ministry of Health (MoH). Our aim was to describe current waiting times and identify opportunities to redistribute service demand among public institutions. Materials and methods. We examined current waiting times and productivity for seven elective surgical and four diagnostic imaging procedures, selected on the basis of their relative frequency and comparability with other national health systems. Results. Mean waiting time for the seven surgical procedures in the three institutions was 14 weeks. IMSS and ISSSTE hospitals showed better performance (12 and 13 weeks) than the MoH hospitals (15 weeks). Mean waiting time for the four diagnostic procedures was 11 weeks. IMSS hospitals (10 weeks) showed better average waiting times than ISSSTE (12 weeks) and MoH hospitals (11 weeks). Conclusion. Substantial variations were revealed, not only among institutions but also within the same institution. These variations need to be addressed in order to improve patient satisfaction.
Objetivo. Se llevó a cabo una evaluación retrospectiva de los tiempos de espera para procedimientos electivos en una muestra de hospitales públicos en México de las siguientes instituciones: Instituto Mexicano del Seguro Social (IMSS), Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) y Secretaría de Salud (SS). El propósito era describir la situación actual en materia de tiempos de espera e identificar oportunidades de redistribución de la demanda de servicios entre instituciones públicas. Material y métodos. Se analizaron los tiempos de espera y la productividad para siete procedimientos quirúrgicos y cuatro procedimientos diagnósticos seleccionados sobre la base de su frecuencia relativa y comparabilidad con otros sistemas de salud nacionales. Resultados. El tiempo de espera promedio para los siete procedimientos quirúrgicos en las tres instituciones fue de 14 semanas. Los hospitales del IMSS y el ISSSTE mostraron un mejor desempeño (12 y 13 semanas) frente a los hospitales de la SS (15 semanas). El tiempo de espera promedio para los cuatro procedimientos diagnósticos fue de 11 semanas. Los hospitales del IMSS mostraron un tiempo de espera promedio mejor (10 semanas) que los hospitales del ISSSTE (12 semanas) y la SS (11 semanas). Conclusión. Se identificaron variaciones importantes no sólo entre instituciones sino también al interior de cada una de ellas. Estas variaciones deben atenderse para así mejorar la satisfacción de los usuarios de los servicios.
Subject(s)
Adult , Aged , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/blood , Models, Biological , Neoplasms/drug therapy , Algorithms , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Area Under Curve , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Capecitabine , Chromatography, High Pressure Liquid , Deoxycytidine/administration & dosage , Deoxycytidine/blood , Deoxycytidine/pharmacokinetics , Dose-Response Relationship, Drug , Floxuridine/blood , Molecular Structure , Neoplasm Metastasis , Neoplasms/metabolism , Neoplasms/pathology , Prodrugs/administration & dosage , Prodrugs/pharmacokinetics , Sesquiterpenes/administration & dosage摘要
The role of neoadjuvant chemoradiation therapy in locally advanced pancreatic cancer (LAPC) is still controversial. The aim of this study was to evaluate surgical downstaging after concurrent chemoradiation therapy (CCRT) for LAPC by measuring the objective changes after treatment. From January 2003 through July 2011, 54 patients with LAPC underwent neoadjuvant CCRT. Computed tomography findings of the tumor size, including major vessel invasion, were analyzed before and after CCRT. Among the total recruited patients, 14 had borderline resectable malignancy and another 40 were unresectable before CCRT. After CCRT, a partial response was achieved in four patients. Stable disease and further disease progression were achieved in 36 and 14 patients, respectively. Tumor size showed no significant difference before and after CCRT (3.6 +/- 1.1 vs. 3.6 +/- 1.0 cm, P = 0.61). Vessel invasion showed improvement in two patients, while 13 other patients showed further tumor progression. Thirty-nine patients with unresectable malignancy and 11 patients with borderline resectable malignancy at time of initial diagnosis remained unchanged after CCRT. Four patients with borderline pancreatic malignancy progressed to an unresectable stage, whereas one unresectable pancreatic malignancy improved to a borderline resectable stage. Only one patient with borderline resectable disease underwent operation after CCRT; however, curative resection failed due to celiac artery invasion and peritoneal seeding. The adverse events associated with CCRT were tolerable. In conclusion, preoperative CCRT in LAPC rarely leads to surgical downstaging, and it could lower resectability rates.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenocarcinoma/diagnostic imaging , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/therapeutic use , Carcinoma, Pancreatic Ductal/diagnostic imaging , Chemoradiotherapy/adverse effects , Combined Modality Therapy , Deoxycytidine/analogs & derivatives , Disease Progression , Fluorouracil/therapeutic use , Neoadjuvant Therapy , Neoplasm Staging , Pancreas/blood supply , Pancreatic Neoplasms/diagnostic imaging , Retrospective Studies , Treatment Outcome摘要
To evaluate the efficacy of combination chemotherapy; gemcitabine and docetaxel, in terms of objective response, in advanced urothelial carcinoma of urinary bladder. Quasi-experimental study. Oncology Department of Combined Military Hospital Rawalpindi, from Oct 2012 to July 2013. Fifty one patients with histologically confirmed urothelialcarcionoma of the bladder were enrolled into this study. Patients were staged and their radiological features were documented before chemotherapy. Four cycles of gemcitabine and docetaxel; combination chemotherapy were administered to the patients. Response was evaluated after 4 courses. Patients with progressive disease were not given further chemotherapy. Patients who could not complete 4 courses were excluded from the study. Remaining patients were given 2 more courses of chemotherapy. Patients were followed up for a period of 1 year after being enrolled for the study to document median survival. Total 46 patients were included in the study out of which 2.2% patients had a complete response, 37% had a partial response, 28.3% patients had a stable disease while 32.6% patients had a progressive disease. The objective response rate was 39.2% while the median survival time was 42 weeks. The results of our study have shown that combination of gemcitabine and docetaxel in patients with advanced urothelial carcinoma of the urinary bladder, has a good therapeutic index and stands as a reasonable first Line option for such patients
Subject(s)
Humans , Male , Female , Deoxycytidine/analogs & derivatives , Taxoids , Antineoplastic Combined Chemotherapy Protocols摘要
Reactivation of Mycobacterium tuberculosis can occur in patients with latent tuberculosis [TB] with risk factors including chronic disease [i.e., malignancy].We herein describe the case of an immigrant from Hong Kong with lung cancer and no known TB disease who presents with reactivation of TB in the setting of chemotherapy and radiation therapy
Subject(s)
Humans , Male , Middle Aged , Antineoplastic Agents , Lung Neoplasms , Radiotherapy , Cisplatin , Deoxycytidine/analogs & derivatives , Tomography, X-Ray Computed , Carcinoma, Squamous Cell摘要
Pancreatic adenocarcinoma is one of the fatalist malignancies. A large proportion of patients are diagnosed with unresectable stage pancreatic cancer at the time of presentation. Gemcitabine is a standard chemotherapeutic agent since 1997, but survival benefit is not satisfactory. Recent clinical study proved that several new combination chemotherapy regimens are superior to gemcitabine single chemotherapy and extended overall survival. However, its prognosis still remains grim. Current research is taking a multidirectional approach in the hope of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. This article also reviews the current ongoing clinical trials, which include the use of molecular targeting agents and immune therapies.
Subject(s)
Humans , Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Immunotherapy , Pancreatic Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use摘要
Objetivo: Identificar na literatura indicações e controvérsias do ATP bioluminescência para avaliação da efetividade da limpeza de superfícies em estabelecimentos de saúde. Método: Revisão integrativa da literatura, entre 2000 e 2012, nas bases de dados MEDLINE, LILACS, Science Direct, SCOPUS e Isi Web of Knowledge. Resultados: Selecionou-se para esta revisão 15 artigos. O ATP bioluminescência foi apontado como importante recurso educacional e método complementar à inspeção visual e às análises microbiológicas na avaliação da efetividade da limpeza. A impossibilidade de indicar a contaminação da superfície por micro-organismos viáveis, a interferência por substâncias químicas e a dificuldade de interpretação dos resultados constituem as principais controvérsias para o uso deste nos serviços de saúde. Conclusão: Apesar de constituir importante recurso na avaliação da limpeza de superfícies, mais estudos são necessários para incorporação efetiva do método nos serviços de saúde. .
Objective: To identify indications and controversies in the literature of the use of ATP bioluminescence to evaluate the effectiveness of surface cleaning in healthcare facilities. Method: Integrative literature review between 2000 and 2012 in the following databases: MEDLINE, LILACS, Science Direct, SCOPUS and Isi Web of Knowledge. Results: were selected for this review 15 articles. The ATP bioluminescence was considered an important educational resource and complementary method to visual inspection and microbiological evaluation of the effectiveness of cleaning. The impossibility to indicate surface contamination by microorganisms, interference by chemicals and the difficulty of interpreting the results constitute the main controversies in the use of ATP in health services. Conclusion: Although this is an important resource in the evaluation of surface cleaning, more studies are necessary for effective incorporation of the method in health services. .
Objetivo: Identificar en la literatura las indicaciones y controversias sobre el uso de la bioluminiscencia ATP para evaluar la eficacia de la limpieza de superficies en los servicios de salud. Método: Revisión integrativa de la literatura, entre 2000 y 2012, en las siguientes bases de datos: MEDLINE, LILACS, Science Direct, SCOPUS e ISI Web of Knowledge. Resultados: Se seleccionaron para esta revisión 15 artículos. La bioluminiscencia del ATP se considera un importante recurso educativo y método complementario a la inspección visual y la análisis microbiológica de la evaluación de la efectividad de la limpieza. La imposibilidad de indicar contaminación de la superficie por los microorganismos, la interferencia por los productos químicos y la dificultad de interpretar los resultados constituyen las principales controversias en la utilización de ATP en los servicios de salud. Conclusión: Aunque esto es un elemento importante en la evaluación de limpieza de superficies, se necesitan más estudios para incorporación eficaz del método en los servicios de salud. .
Subject(s)
Animals , Male , Mice , Antineoplastic Agents/pharmacology , Deoxycytidine/analogs & derivatives , Floxuridine/pharmacology , Intestines/drug effects , Prodrugs/pharmacology , Deoxycytidine/pharmacology , Floxuridine/metabolism , Floxuridine/toxicity , Fluorouracil/metabolism , Fluorouracil/pharmacology , Fluorouracil/toxicity , Mice, Inbred Strains , Neoplasms, Experimental/drug therapy , Prodrugs/toxicity摘要
This study aimed to evaluate, by scanning electron microscopy (SEM), the cleaning of canal walls with moderate curvature subjected to biomechanical preparation with different final diameters using apical negative pressure irrigation. Thirty-two mesiobuccal roots of molars were divided into 4 groups (n=8) according to the instrument's final diameter: GI: 30.02, GII: 35.02, GIII: 40.02 and GIV: 45.02. Irrigating procedure was performed at each change of instrument with 1% NaOCl using the Endovac system. Final irrigation was conducted with 17% EDTA for 5 min. The SEM photomicrographs were evaluated under 35× and 1000× magnification, by three calibrated examiners, in a double-blind design. Data were submitted to Kruskal-Wallis and Dunn's post hoc tests (α=0.05). Canals instrumented with 30.02 and 35.02 final diameters showed more debris, statistically different from the other groups (p<0.05). Comparing each root canal third, for the cervical and apical portions no statistically significant difference (p>0.05) was found among the four groups. Regarding the presence of smear layer, canals with 30.02 final diameter showed the highest scores, statistically different from the 45.02 group (p<0.05) and similar to the 35.02 and the 40.02 groups (p>0.05). Although none of the studied diameters completely removed debris and smear layer, it may be concluded that instrumentation with higher final diameters was more effective in cleaning the root canals with moderate curvature.
Este estudo buscou avaliar, por meio de microscopia eletrônica de varredura (MEV), a limpeza das paredes de canais com curvatura moderada, submetidos ao preparo biomecânico com diferentes diâmetros finais utilizando-se irrigação por pressão apical negativa. Trinta e duas raízes mésio-vestibulares de molares foram divididas em 4 grupos (n=8) de acordo com o diâmetro final dos instrumentos: GI: 30.02, GII: 35.02, GIII: 40.02 e GIV: 45.02. O procedimento de irrigação foi realizado a cada troca de instrumento com NAOCl 1% utilizando o sistema EndoVac. A irrigação final foi conduzida com EDTA 17% por 5 min. As microfotografias de MEV foram avaliadas sob aumentos de 35× e 1000×, por três examinadores calibrados, em estudo duplo-cego. Os dados foram submetidos ao teste de Kruskal-Wallis e pós-teste de Dunn (=0,05). Os canais instrumentados com diâmetros finais de 30.02 e 35.02 demonstraram mais debris, estatisticamente diferente dos demais grupos (p<0,05). Comparando-se cada terço do canal radicular, para as porções cervical e apical não foi encontrada diferença estatisticamente significante (p>0,05) entre os quatro grupos. Com relação à presença de smear layer, canais com diâmetro final de 30.02 demonstraram os maiores scores, estatisticamente diferente do grupo 45.02 (p<0,05) e similar aos grupos 35.02 e 40.02 (p>0,05). Apesar de nenhum dos diâmetros estudados ter removido completamente os debris e a smear layer, pode ser concluído que a instrumentação com diâmetros finais maiores foi mais efetiva na limpeza dos canais radiculares com curvatura moderada.
Subject(s)
Humans , Antimetabolites, Antineoplastic/therapeutic use , Chemotherapy, Adjuvant , Colorectal Neoplasms/enzymology , Deoxycytidine/analogs & derivatives , Floxuridine/therapeutic use , Oxidoreductases/biosynthesis , Thymidine Phosphorylase/biosynthesis , Capecitabine , Colorectal Neoplasms/mortality , Dihydrouracil Dehydrogenase (NADP) , Disease-Free Survival , Deoxycytidine/therapeutic use , Enzyme-Linked Immunosorbent Assay , Fluorouracil/analogs & derivatives , Recurrence , Time Factors摘要
A 55-year-old woman on treatment with capecitabine and paclitaxel for breast carcinoma presented with history of a tingling sensation in her hands and feet with a progressive burning sensation. She also noted discomfort, minimal pain and stiffness while holding objects. On examination, there was patchy hyperpigmentation of both the palms and soles, and the dorsa of hands and feet. This was accompanied by a thickening of the skin more over the knuckles and toes. In addition there was a moist desquamation around the toes and over the palmar creases and a bluish discoloration of the lunulae of both thumbnails. She was diagnosed with hand and foot syndrome and started on pyridoxine and emollients. The finding of keratoderma noted in our patient is not seen commonly in hand and foot syndrome.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Foot , Hand , Humans , Hyperpigmentation/chemically induced , Keratoderma, Palmoplantar/chemically induced , Middle Aged , Paresthesia/chemically induced , Syndrome摘要
Context Capecitabine, an oral drug, is as effective as traditional chemotherapy drugs. Objectives To investigate the adhesion to treatment with oral capecitabine in breast and colorectal cancer, and to determine any correlation with changes in patient’s quality of life. Methods Patients with colorectal cancer or breast cancer using capecitabine were included. The patients were asked to bring any medication left at the time of scheduled visits. The QLQ-C30 questionnaire was applied at the first visit and 8-12 weeks after treatment. Results Thirty patients were evaluated. Adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No strong correlation between adherence and European Organisation for Research and Treatment of Cancer QLQ-C30 functional or symptom scale rates had been found. There was no statistically significant correlation between compliance and the functional and symptom scales of the questionnaire before and after chemotherapy, with the exception of dyspnea. Conclusions Although no absolute adherence to oral capecitabine treatment had been observed, the level of adherence was good. Health professionals therefore need a greater focus in the monitoring the involvement of patients with oral treatment regimens. Patients with lesser degrees of dyspnea had greater compliance. .
Contexto A capecitabina, uma droga oral, é tão eficaz quanto as drogas quimioterápicas tradicionais. Objetivos Investigar a adesão ao tratamento oral com capecitabina para câncer de mama e colorretal e determinar qualquer correlação com as mudanças na qualidade de vida do paciente. Métodos Pacientes com câncer colorretal ou de mama em uso de capecitabina foram incluídos. A cada consulta os pacientes trouxeram a medicação restante. O questionário de qualidade de vida QLQ- C30 foi aplicado na primeira visita e 8-12 semanas após o tratamento. Resultados Trinta pacientes foram avaliados. A adesão foi de 88,3% para o câncer de cólon metastático, 90,4% para o de cólon não-metastático, 94,3% para o de reto e 96,2% para o de mama metastático. Com exceção da dispnéia, não houve forte correlação entre adesão e as taxas European Organisation for Research and Treatment of Cancer QLQ-C30 em relação a escala funcional ou de sintomas no início ou após quimioterapia. Conclusões O nível de adesão foi bom, embora não houvesse adesão absoluta ao tratamento com capecitabina oral. Os profissionais de saúde, portanto, precisam dar maior atenção a pacientes em regimes de tratamento oral. Os pacientes com menor grau de dispneia tiveram maior adesão. Neoplasias colorretais, terapia .
Subject(s)
Female , Humans , Male , Middle Aged , Antimetabolites, Antineoplastic/administration & dosage , Breast Neoplasms/drug therapy , Colonic Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Medication Adherence/statistics & numerical data , Rectal Neoplasms/drug therapy , Administration, Oral , Cohort Studies , Deoxycytidine/administration & dosage , Fluorouracil/administration & dosage , Prospective Studies , Surveys and QuestionnairesSubject(s)
Animals , Male , Mice , Bone Marrow/drug effects , Deoxycytidine/analogs & derivatives , Floxuridine/toxicity , Immunosuppressive Agents/toxicity , Thymus Gland/pathology , Body Weight/drug effects , Corticosterone/blood , Deoxycytidine/toxicity , Dose-Response Relationship, Drug , Immunohistochemistry , Isomerism , Organ Size/drug effects , Reticulocyte Count/drug effects摘要
Debido a la inespecificidad de los síntomas, el cáncer gástrico (CG) es diagnosticado frecuentemente en etapas avanzadas, lo que da cuenta de los altos índices de mortalidad debido a esta neoplasia a nivel mundial. El esquema de tratamiento adyuvante o neoadyuvante en los países occidentales incluye el uso de fluoropirimidinas citotóxicas y compuestos de platino formadores de aductos en el ADN. La respuesta clínica al tratamiento con estos fármacos depende principalmente de la sensibilidad del tumor, la cual a su vez está condicionada por el nivel de expresión de los blancos terapéuticos y de las enzimas de reparación del ADN. Sumado a esto, algunos polimorfismos de línea germinal en genes asociados al metabolismo y a la respuesta a estos fármacos, han mostrado asociación con respuestas pobres y con el desarrollo de eventos adversos, incluso con resultados fatales. La identificación de biomarcadores genómicos, en la forma de polimorfismos genéticos o la expresión diferencial de genes específicos asociados a la respuesta quimioterapeútica ha sido motivo de intensa investigación como base para la aplicación de la farmacogenómica en el establecimiento de una terapia farmacológica racional y personalizada del CG. Sin embargo, ante la eventual aplicación de la farmacogenómica en el ámbito clínico, es necesario establecer el valor pronóstico real de dichos biomarcadores mediante los estudios de asociación genotipo-fenotipo, así como su prevalencia en el contexto de cada población de pacientes. Estos aspectos son indispensables al evaluar la relación costo-efectividad de la introducción de los productos de la medicina genómica predictiva en el tratamiento del CG.
Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.
Subject(s)
Humans , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Antineoplastic Agents/classification , Biomarkers , Biological Transport/genetics , Biotransformation/genetics , Combined Modality Therapy , Drug Combinations , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacokinetics , Deoxycytidine/therapeutic use , Drug Resistance, Neoplasm/genetics , Enzymes/genetics , Ethnicity/genetics , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Fluorouracil/pharmacokinetics , Fluorouracil/therapeutic use , Gastrectomy , Mexico , Molecular Targeted Therapy , Organoplatinum Compounds/pharmacokinetics , Oxonic Acid/pharmacokinetics , Patient Selection , Pharmacogenetics , Precision Medicine , Prodrugs/pharmacokinetics , Stomach Neoplasms/genetics , Stomach Neoplasms/surgery , Tegafur/pharmacokinetics摘要
BACKGROUND: Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since a relevant percentage of pancreatic cancer patients present with non‑metastatic but locally advanced disease. The objective of the present study was to assess the effect of neoadjuvant chemoradiation therapy (NACRT) on tumor response, down staging and resection, toxicity and any survival advantage. MATERIALS AND METHODS: A prospective pilot study was carried out from January 2009 to June 2011 in which 15 patients of locally advanced unresectable pancreatic cancer were included. All patients were treated with NACRT protocol with oral Capecitabine and 3D conformal radiotherapy (3DCRT) of 30 Gy in 10 fractions. The patients were restaged 3 to 4 weeks after the completion of NACRT and explored for resection. RESULTS: Out of 15 patients, fourteen were evaluable. Four patients underwent surgery, 5 had partial response but remained unresectable, 2 patients had stable disease and 3 had progressive disease. Most of the toxicities were slight and were in grade 1 to 2. None of the patients developed grade 3 or 4 gastrointestinal or hematological toxicity. The median survival was 15 months for resected patients and 8.6 months for unresected patients, respectively. The 2 year actuarial overall survival was 34.6%. CONCLUSION: All patients with locally unresectable pancreatic cancer should be offered chemoradiation therapy, in hopes of down staging the tumor for possible resection and achieving higher survival.
Subject(s)
Aged , Antineoplastic Agents/administration & dosage , Chemoradiotherapy/methods , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Feasibility Studies , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Male , Middle Aged , Neoadjuvant Therapy/methods , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Pilot Projects , Prospective Studies , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Conformal , Tertiary Care Centers摘要
Colorectal cancer is the third most common cancer worldwide. Survival and prognosis depend on tumor stage upon diagnosis, and in more than 50% of cases, the tumor has already invaded adjacent tissues or metastasis has occurred. Aiming to improve diagnosis, clinical prognosis and treatment of patients with colorectal cancer, several studies have investigated microRNAs as molecular markers of the disease due to their potential regulatory functions on tumor suppressor genes and oncogenes. This review aimed to summarize the main topics related to the use of microRNAs in diagnosis, clinical prognosis and evaluating treatment response in colorectal cancer.
O câncer colorretal é o terceiro tipo de câncer mais comum em todo o mundo. A sobrevivência e o prognóstico dependem do estágio do tumor no diagnóstico, momento em que, em mais de 50% dos casos, o tumor já invadiu tecidos adjacentes ou ocorreu metástase. Objetivando-se melhorar o diagnóstico, o prognóstico clínico e o tratamento de pacientes com câncer colorretal, vários estudos investigaram microRNAs como marcadores moleculares da doença, devido à sua função reguladora potencial sobre genes supressores de tumor e oncogenes. Esta revisão procura resumir os principais tópicos relacionados ao uso de microRNAs no diagnóstico, na determinação do prognóstico clínico e na avaliação de resposta ao tratamento do câncer colorretal.