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Article in English | WPRIM | ID: wpr-887717


Objective@#To investigate the molecular mechanism of high phosphorylation levels of cofilin-1 (p-CFL-1) associated with paclitaxel resistance in epithelial ovarian cancer (EOC) cells.@*Methods@#Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA interference. Cell inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8 (CCK-8) assay. Apoptosis was assessed by flow cytometry and protein levels were detected by western blotting. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of phosphokinases and phosphatases of CFL-1. Survival analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1 (SSH-1).@*Results@#High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of paclitaxel. SKOV3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy, as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein expression. Cytoplasmic accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial apoptosis. SSH-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 cells. Clinically, the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC patients.@*Conclusion@#The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.

Female , Humans , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis , Carcinoma, Ovarian Epithelial/metabolism , Cell Line, Tumor , Cofilin 1/metabolism , Drug Resistance, Neoplasm , Ovarian Neoplasms/metabolism , Paclitaxel/therapeutic use , Phosphoprotein Phosphatases/metabolism , Phosphorylation
Acta cir. bras ; 34(3): e201900305, 2019. graf
Article in English | LILACS | ID: biblio-989062


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

Animals , Male , Rats , Stomach Neoplasms/drug therapy , Plant Extracts/therapeutic use , Adenocarcinoma/drug therapy , Usnea/chemistry , Acetates/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Rats, Wistar , Neoplasms, Experimental/drug therapy
Braz. j. med. biol. res ; 52(11): e8657, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039263


Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.

Humans , Female , Breast Neoplasms/metabolism , Paclitaxel/metabolism , HMGB1 Protein/metabolism , MicroRNAs/metabolism , MCF-7 Cells/metabolism , Antineoplastic Agents, Phytogenic/metabolism , Autophagy/genetics , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic/genetics , Up-Regulation/genetics , Paclitaxel/therapeutic use , Apoptosis/genetics , Drug Resistance, Neoplasm/genetics , HMGB1 Protein/genetics , MicroRNAs/genetics , Antineoplastic Agents, Phytogenic/therapeutic use
Rev. Assoc. Med. Bras. (1992) ; 64(3): 230-233, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-896447


Summary Objective: The current study aimed to investigate the clinical efficacy of paclitaxel combined with avastin for non-small cell lung cancer (NSCLC) patients diagnosed with malignant pleural effusion (MPE). Method: Total of 33 patients diagnosed with NSCLC as well as malignant pleural effusion were included. All of them received paclitaxel (175 mg/m2) and avastin (5 mg/kg). Clinical efficacy was evaluated using the total response rate, overall survival, progression-free survival and changes in MPE volume. Adverse events and rates of toxicities were examined as well. Results: The total response rate reached 77% while the overall survival and the median progression-free survival were respectively 22.2 months and 8.4 months. Toxicities of grade 3-4 consisted of neutropenia in 57% of patients, anemia in 17% of them, febrile neutropenia in 11%, as well as anorexia in 7%. No treatment-correlated deaths were found. Conclusion: Paclitaxel combined with avastin decreased MPE volume and increased survival rate of NSCLC patients via inhibiting vascular endothelial growth factor expression.

Humans , Male , Female , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Paclitaxel/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Lung Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/therapeutic use , Quality of Life , Safety , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Survival Analysis , Pleural Effusion, Malignant/drug therapy , Treatment Outcome , Paclitaxel/adverse effects , Disease-Free Survival , Angiogenesis Inhibitors/adverse effects , Bevacizumab/adverse effects , Middle Aged , Antineoplastic Agents, Phytogenic/adverse effects
Medicina (B.Aires) ; 77(4): 283-290, ago. 2017. ilus, graf, tab
Article in English | LILACS | ID: biblio-894480


Higher plants have provided various natural derived drugs used currently in western medicine. Tessaria absinthioides (Hook. & Arn.) DC, Asteraceae, is a native plant from South-America with reported ethnopharmacological and culinary uses. Despite recent scientific reports about plants properties, there is not a well conducted research about its anticancer and potential toxic effects. The current work demonstrates the plant aqueous extract composition; the in vitro induced cytotoxicity, and explores, in vivo, its oral toxicity and antitumoral effects. Composition of aqueous extract was determined by phytochemical reactions. Cytotoxicity was tested in tumoral (Hela, Gli-37, HCT-116 and MCF-7) and non-tumoral (HBL-100) cells, using MTT assay. Oral toxicity and the antitumor activity against colorectal carcinoma were studied in rodents. The chemical analysis revealed the presence of flavonoids, carbohydrates, sterols, terpenes and tannins. Cytotoxicity towards tumoral cells was observed (CV50: 3.0 to 14.8 μg/ml); while in non-tumoral cells, extracts evidenced a selective reduced toxicity (CV50: 29.5 μg/ml). Oral administration of the extract does not induce acute nor dose-repeated toxicity at doses up to 2000 mg/kg and 1000 mg/kg/day, respectively. The antitumoral effect was confirmed by a significant increase in a median survival from 24 weeks (non-treated) to 30 weeks (T. absinthioides treated). The present data indicate that T. absinthioides extract exhibits cytotoxicity against cancer cell lines, with no-toxic effects and significant antitumoral effects in colorectal cancer when is orally administrated. In conclusion, T. absinthioides possesses selective cytotoxicity and antitumoral activities, making its plant derivatives products promising for cancer research and treatment.

Las plantas superiores han provisto numerosos derivados naturales usados actualmente por la medicina occidental. Tessaria absinthioides (Hook & Arn) DC, Asteraceae, es una planta autóctona de Sudamérica con informes de uso etnofarmacológico y culinario. A pesar de los reportes científicos sobre las propiedades de esta planta, no existen estudios que caractericen sus efectos antitumorales ni sus efectos tóxicos. En el presente trabajo se describe la composición del extracto acuoso de T. absinthioides, sus propiedades citotóxicas in vitro, y explora in vivo la toxicidad oral y su capacidad de afectar la progresión de tumores. La composición se determinó mediante reacciones fitoquímicas. La citotoxicidad se estudió en líneas celulares tumorales (Gli-37, HeLa, HCT-116 y MCF-7) y no tumorales (HBL-100), utilizando el ensayo de MTT. La toxicidad oral de los extractos y su capacidad antitumoral sobre carcinoma colorrectal se analizaron en roedores. El análisis del extracto acuoso evidenció flavonoides, carbohidratos, esteroles, terpenos y taninos. La citotoxicidad sobre células tumorales resultó similar a la observada para el 5-fluoracilo (CV50: 3.0 a 14.8 μg/ml); mientras que, en células no tumorales, el efecto estuvo selectivamente reducido (CV50: 29.5 μg/ml). La administración oral del extracto no indujo toxicidad aguda ni a dosis repetidas (dosis hasta 2000 mg/kg y 1000 mg/kg/día, respectivamente). Los efectos antitumorales se confirmaron mediante un significativo aumento de la supervivencia en el grupo tratado con T. absinthioides. En conclusión, de acuerdo a los resultados obtenidos, T. absinthioides y sus derivados naturales representan un campo prometedor de estudio para la investigación en el tratamiento del cáncer.

Animals , Rabbits , Rats , Plant Extracts/pharmacology , Colorectal Neoplasms/drug therapy , Asteraceae/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Tetrazolium Salts , Plant Extracts/therapeutic use , Colorectal Neoplasms/pathology , Rats, Sprague-Dawley , Toxicity Tests , Cell Line, Tumor , Disease Models, Animal , Fluorouracil , Mice, Inbred BALB C , Antineoplastic Agents, Phytogenic/therapeutic use
Rev. cuba. plantas med ; 21(4)oct.-dic. 2016. ilus, tab
Article in Spanish | LILACS, CUMED | ID: biblio-960662


Introducción: la curcumina es el principal compuesto polifenólico bioactivo de la planta Curcuma longa. Esta molécula ha mostrado efectos antioxidantes, anti-inflamatorios y anticancerígenos en diferentes modelos experimentales. Como parte de su actividad benéfica en células tumorales, se le ha asociado con la regulación de mecanismos epigenéticos, modulando así diferentes vías de señalización, entre ellas la vía Wnt/ß-catenina, la cual juega un papel fundamental en el desarrollo de cáncer. Objetivos: describir los avances científicos en el estudio de la actividad anti-cancerígena de la curcumina en relación a la modulación de mecanismos epigenéticos y su implicación en la vía Wnt/ß-catenina. Métodos: se realizó una búsqueda sistemática en las bases de datos PubMed, Google Scholar, Scopus y ScienceDirect, utilizando los siguientes criterios de búsqueda: curcumina, epigenética, Wnt/ß-catenina y cáncer. Se incluyeron artículos con importancia científica entre los años 2001-2016, que exploraran la actividad inhibitoria de la curcumina sobre la maquinaria epigenética y/o que evidenciaran un efecto regulador sobre alteraciones en la vía Wnt/ß-catenina. Resultados: se encontró en la literatura una creciente evidencia que involucra a la curcumina con la inhibición de la actividad de enzimas ADN metiltransferasas, acetiltransferasas y desacetilasas de histonas, y por ende en la regulación de alteraciones epigenéticas. Esto lleva a la re-expresión de genes silenciados en diversos tipos de cáncer, lo cual le confiere una actividad antitumoral asociada a la regulación de vías de señalización. En este contexto, se ha demostrado que la curcumina actúa sobre componentes de la vía Wnt/ß-catenina e incluso regula su actividad mediante la desmetilación de antagonistas de Wnt. Conclusiones: este manuscrito discute los potenciales efectos quimiopreventivos de la curcumina asociados con restauración de los mecanismos epigenéticos y la vía de señalización Wnt/ß-catenina(AU)

Introduction: Curcumin is the main bioactive polyphenolic compound in the plant Curcuma longa. This molecule has displayed antioxidant, anti-inflammatory and anti-cancer activity in various experimental models. Its beneficial effect on tumor cells has been associated with the regulation of epigenetic mechanisms, modulating various signaling pathways, among them the Wnt/-catenin pathway, which plays a fundamental role in cancer development. Objectives: Describe the scientific progress achieved in the study of the anti-cancer activity of curcumin in relation to the modulation of epigenetic mechanisms and its implication for the Wnt/?-catenin pathway. Methods: A systematic search was conducted in the databases PubMed, Google Scholar, Scopus and ScienceDirect, using the search terms curcumin, epigenetics, Wnt/?-catenin and cancer. Papers were included which had scientific relevance, had been published between 2001 and 2016, explored the inhibitory activity of curcumin on the epigenetic machinery and/or presented evidence of a regulatory effect on alterations in the Wnt/?-catenin pathway. Results: Growing evidence was found in the literature associating curcumin with inhibition of the activity of the enzymes histone deacetylases, acetyltransferases and DNA methyltransferases, and therefore regulation of epigenetic alterations. This leads to re-expression of silenced genes in various cancer types, granting it antitumor activity associated with the regulation of signaling pathways. In this context, it has been proved that curcumin acts upon components of the Wnt/?-catenin pathway and even regulates their activity through demethylation of Wnt antagonists. Conclusions: The paper discusses the potential chemopreventive effects of curcumin associated with restoration of epigenetic mechanisms and the Wnt/-catenin signaling pathway(AU)

Humans , Curcumin/therapeutic use , Epigenomics , Antineoplastic Agents, Phytogenic/therapeutic use
Einstein (Säo Paulo) ; 14(3): 420-422, July-Sept. 2016. graf
Article in English | LILACS | ID: lil-796978


ABSTRACT A 69-year-old male patient, smoker, was diagnosed with small cell lung cancer metastatic to lung, liver and central nervous system. He received chemotherapy with carboplatin AUC 5 on day 1 and etoposide 100mg/m2 on days 1, 2 and 3. During the first cycle, the patient presented with febrile neutropenia and abdominal distension. Chest, abdomen and pelvis computed tomography scan was performed and detected gas dissecting the wall of sigmoid colon extending to the mesosigmoid. Patient had no abdominal pain, nausea, vomiting, and on physical examination he had no peritoneal irritation, tachycardia or hemodynamic instability compatible with perforation or acute abdomen. Therefore, the radiological finding was interpreted as pneumatosis intestinalis caused by chemotherapy with etoposide. Pneumatosis resolved after continuous oxygen therapy. The second cycle was administered after a complete resolution of the clinical condition and etoposide dose was reduced by 30%. The patient experienced a remarkable evolution.

RESUMO Paciente do gênero masculino, 69 anos, fumante, diagnosticado com câncer de pulmão de pequenas células, metastático para pulmão, fígado e sistema nervoso central. Foi administrada quimioterapia com carboplatina AUC 5 no dia 1 e etoposídeo 100mg/m2 nos dias 1, 2 e 3. Durante o primeiro ciclo, o paciente apresentou neutropenia febril e distensão abdominal. Tomografias de tórax, abdome e pelve detectaram gás dissecando a parede do cólon sigmoide, com extensão para o mesossigmoide. O paciente não apresentava dor abdominal, náusea, vômito e não tinha sinais de irritação peritoneal, taquicardia ou instabilidade hemodinâmica compatíveis com perfuração ou abdome agudo. O achado radiológico foi interpretado como pneumatose intestinal causada por etoposídeo. A resolução do quadro ocorreu após suplementação de oxigênio. O segundo ciclo foi administrado após resolução completa do quadro, com redução da dose do quimioterápico em 30%. O paciente evoluiu de forma bastante satisfatória.

Humans , Male , Aged , Pneumatosis Cystoides Intestinalis/chemically induced , Carcinoma, Non-Small-Cell Lung/drug therapy , Etoposide/adverse effects , Lung Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/adverse effects , Oxygen Inhalation Therapy , Pneumatosis Cystoides Intestinalis/therapy , Carcinoma, Non-Small-Cell Lung/secondary , Etoposide/therapeutic use , Lung Neoplasms/secondary , Antineoplastic Agents, Phytogenic/therapeutic use
Rev. bras. epidemiol ; 18(1): 248-261, Jan-Mar/2015. tab, graf
Article in Portuguese | LILACS | ID: lil-736433


OBJETIVO: Analisar as desigualdades socioeconômicas na utilização de consultas médicas (CM) no último ano no Brasil. MÉTODOS: Dados da Pesquisa Nacional por Amostra de Domicílios (≥ 20 anos de idade) das Regiões Nordeste (2003, n = 75.652 e 2008, n = 79.779) e Sudeste (2003, n = 76.029 e 2008, n = 79.356) foram analisados segundo CM. Compararam-se as prevalências de CM segundo as variáveis exploratórias demográficas e de saúde no primeiro (D1) e último (D10) decil de renda familiar per capita. As análises consideraram o desenho amostral complexo. RESULTADOS: A proporção de pessoas com CM aumentou no período na Região Nordeste (61,2 para 66,9%) e Sudeste (67,9 para 73,5%). A diferença absoluta de CM, segundo D1 e D10 no período, foi de 6,4 pontos percentuais (pp) no Nordeste e 4,2 pp no Sudeste. Houve importante redução das desigualdades entre os homens; naqueles sem doenças crônicas; naqueles que tinham uma percepção positiva da sua saúde e naqueles sem plano de saúde com direito a CM. A Região Sudeste ainda apresentou redução entre aqueles com apenas uma morbidade autorreferida (8 pp) e com percepção negativa da saúde (6 pp). CONCLUSÃO: Houve aumento de CM no Brasil. Observa-se ainda persistente desigualdade entre os mais pobres e os mais ricos, maior no Nordeste do que no Sudeste. Políticas para a redução da desigualdade em saúde mais eficazes e equânimes devem ser adotadas no Brasil. .

OBJECTIVE: To analyze the socioeconomic inequalities in medical visits (MV) in the past year in Brazil. METHODS: Data from adults aged ≥ 20 years old who participated in the Brazilian National Household Surveys and living in the Northeastern (2003; n = 75,652 and 2008, n = 79,779) and Southeastern (2003; n = 76,029 and 2008; n = 79,356) regions were analyzed according to MV. We compared MVs according to demographic and health variables in the first (D1) and last (D10) per capita family income deciles. All analyses considered the complex cluster design. RESULTS: The proportion of people who had MV during this period increased in the Northeastern (from 61.2 to 66.9%) and the Southeastern (from 67.9 to 73.5%) regions. The absolute difference (AD) in the use of MV, according to D1 and D10 in this period, was equal to 6.4 percentage points (pp) in the Northeastern and 4.2 pp in the Southeastern regions. Significant reduction in inequalities was observed among men without chronic diseases, in those who had a positive perception of their health, and among those without health insurance which included MV. The Southeastern region has also showed significant reduction among those with chronic disease (8 pp) and with negative health self-perception (6 pp). CONCLUSION: The increasing number of MVs was found in Brazil. However, persistent inequalities were observed between the poorest and the richest, higher in the Northeastern than in the Southeastern region. More effective and equitable policies to reduce health inequalities should be adopted in Brazil. .

Animals , Female , Humans , Mice , Adenocarcinoma/pathology , Colonic Neoplasms/pathology , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Neoplasm Metastasis/pathology , Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Adhesion , Cell Line, Tumor , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Collagen Type II/metabolism , Colonic Neoplasms/drug therapy , Fibronectins/metabolism , Floxuridine/therapeutic use , Fluorouracil/therapeutic use , Laminin/metabolism , Liver Neoplasms/drug therapy , Mice, Nude , Models, Biological , Neoplasm Metastasis/prevention & control , Paclitaxel/therapeutic use
Acta cir. bras ; 28(3): 185-189, Mar. 2013. ilus, tab
Article in English | LILACS | ID: lil-667928


PURPOSE: To investigate the immunohistochemistry of the uterine cervix of 20 Wistar rats (Rattus norvegicus) bearing the Walker 256 tumor, treated with copaiba oil (Copaifera officinalis). METHODS: The animals were grouped into four subgroups, with five rats each: the GCT and GCopT received distilled water and topically copaiba, respectively, while the GCG and GCopG received distilled water and copaiba by gavage, respectively. The substances were administered for nine days. On the 12th day, after euthanasia, the tumor pieces were sent to the identification of T CD4+, T CD8+ and Natural Killer cells. RESULTS: It was found that the pattern of expression for specific markers of phenotypes of cells involved in tumor immune response was similar in all groups, regardless the administration way of copaiba oil (topical or gavage). CONCLUSION: Copaiba balsam, administered either topically or by gavage, did not alter the pattern of tumor immune response in rats bearing Walker 256 Tumor.

Animals , Female , Rats , Antineoplastic Agents, Phytogenic/therapeutic use , Balsams/therapeutic use , /drug therapy , Cervix Uteri/drug effects , /immunology , /pathology , Cervix Uteri/immunology , Cervix Uteri/pathology , Immunohistochemistry , Random Allocation , Rats, Wistar , Reproducibility of Results , Time Factors , Treatment Outcome
Braz. j. med. biol. res ; 45(6): 524-530, June 2012. ilus, tab
Article in English | LILACS | ID: lil-622774


The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µM and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µM. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract.

Animals , Humans , Mice , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Chalcone/pharmacology , In Vitro Techniques , Neoplasms/drug therapy , Phytotherapy/methods , Zingiberaceae/chemistry , Analysis of Variance , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Antioxidants/therapeutic use , Cell Line, Tumor , Chromatography , Chalcone/isolation & purification , Drug Screening Assays, Antitumor/methods , Rhizome
Article in English | WPRIM | ID: wpr-178283


We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/microL with body temperature over 38degrees C; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.

Adult , Humans , Male , Middle Aged , Age Factors , Antineoplastic Agents, Phytogenic/therapeutic use , Body Temperature , CD4 Lymphocyte Count , Fever/etiology , HIV Infections/complications , Lymphoma, AIDS-Related/complications , Multivariate Analysis , Neutropenia/etiology , Retrospective Studies , Risk Factors , Vincristine/therapeutic use
Braz. oral res ; 25(6): 519-525, Nov.-Dec. 2011. ilus
Article in English | LILACS | ID: lil-608020


Squamous cell carcinoma (SCC) is the most prevalent cancer of the oral cavity and the fifth most prevalent of all malignancies in males. Many researchers have attempted to develop new treatments that will improve the prognosis of SCC patients. Over 20 percent of the world's biodiversity is located within the Brazilian forests, but little is known about the chemical and/or pharmacological potential of these plants. Certain extracts obtained from Amazon and Atlantic Forest plants have previously been shown to have cytotoxic activity against various cancers. The aim of this study was to screen these extracts for cytotoxic activity against oral SCC cells. The extracts were analyzed for activity against the KB-ADL#12 cell line at various concentrations up to a maximum dose of 100 µg/mL. Comparisons with a control group were performed using one-way ANOVA. Significant cytotoxicity was induced by the extracts obtained from the aerial parts of Picrolemma sprucei (Simaroubaceae), from the leaves and stems of Laetia suaveolens (Salicaceae), from the aerial parts of Abarema auriculata (Fabaceae-Mimosoideae) and from the stem of A. auriculata.

Humans , Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Mouth Neoplasms/drug therapy , Plant Extracts/therapeutic use , Plants, Medicinal/chemistry , Analysis of Variance , Magnoliopsida/chemistry , Brazil , Cell Count , Cell Culture Techniques , Cell Line, Tumor , Drug Screening Assays, Antitumor/methods , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Stems/chemistry , Time Factors
Biol. Res ; 44(3): 243-249, 2011. ilus
Article in English | LILACS | ID: lil-608620


Cimicifuga foetida, an Asian Cimicifuga species, has been employed as a cooling and detoxification agent in traditional Chinese medicine since ancient times. For this herb, two cycloartane triterpene glycosides isolated from the rhizomes have demonstrated cytotoxicity on rat tumor and human cancer cell lines. Since human Hsp27 is increased in various human cancers and exhibits cytoprotective activity that affects tumorigenesis and the susceptibility of tumours to cancer treatment, the purpose of this research was to study the expression of this protein in MCF-7 breast cancer cells. To accomplish this aim, MCF-7 cells were exposed to different concentrations of Cimicifuga foetida extract showing a reduction in cell number measured by the sulforhodamine assay. In addition, the expression of Hsp-27 mRNA detected by RT-PCR and Hsp-27 protein detected by immnofluorescence was present in all conditions, except when using the highest concentration of Cimicifuga foetida extract (2,000 jig /L). We conclude that Hsp 27 expression at 2,000 jig /L Cimicifuga foetida extract is diminished. This is the first report showing the Hsp-27 expression after exposure to Cimicifuga foetida extract in MCF-7 cells.

Adult , Animals , Cattle , Female , Humans , Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Cimicifuga/chemistry , /metabolism , Phytotherapy , Plant Extracts/therapeutic use , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Blotting, Western , Breast Neoplasms/metabolism , Fluorescent Antibody Technique , Plant Extracts/analysis , Reverse Transcriptase Polymerase Chain Reaction
J. bras. pneumol ; 36(5): 588-594, set.-out. 2010. tab
Article in Portuguese | LILACS | ID: lil-564201


OBJETIVO: Avaliar o efeito da quimioterapia sobre a condição física de pacientes com câncer de pulmão avançado. MÉTODOS: Foram avaliados 50 pacientes com câncer de pulmão não pequenas células nos estágios IIIB e IV e com status de performance segundo a escala do Eastern Cooperative Oncology Group (ECOG) entre zero e dois. Todos receberam quimioterapia com as drogas paclitaxel e derivados da platina e foram avaliados em três momentos (pré-quimioterapia, pós-quimioterapia e seis meses após o início do tratamento), nos quais a escala ECOG, o índice de massa corpórea (IMC) e a Distância percorrida no Teste de Caminhada de Seis minutos (DTC6) foram avaliados. RESULTADOS: Dos 50 pacientes incluídos, 14 foram a óbito, 5 foram excluídos do estudo por apresentar piora do status de performance, e 31 concluíram o seguimento de seis meses. Não houve diferença estatisticamente significativa para o IMC (p = 1,00, pré-quimioterapia vs. pós-quimioterapia; e p = 0,218, pré-quimioterapia vs. seis meses após) ou para a DTC6 entre os momentos de avaliação. O status de performance melhorou, principalmente com o aumento do número de pacientes assintomáticos após seis meses de acompanhamento (p = 0,031). CONCLUSÕES: O uso de quimioterapia teve um efeito benéfico no status de performance dos pacientes. Não houve alterações no IMC ou na DTC6 durante o período do estudo, o que pode sugerir a manutenção da condição física dos pacientes.

OBJECTIVE: To evaluate the effect of chemotherapy on the physical condition of patients with advanced lung cancer. METHODS: We evaluated 50 patients with non-small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology Group (ECOG) performance status scale scores between zero and two. All patients underwent chemotherapy using paclitaxel and platinum derivatives and were evaluated at three time points (prechemotherapy, postchemotherapy and six months after starting the treatment), at which the ECOG scale, the body mass index (BMI) and the six-minute walk distance (6MWD) were assessed. RESULTS: Of the 50 patients included in the study, 14 died, 5 were excluded due to the worsening of their performance status, and 31 completed the six-month follow-up. There was no statistically significant difference between the time points of assessment for BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six months later, p = 0.218) or for 6MWD. Performance status improved, and this was especially due to the increase in the number of asymptomatic patients after the six-month follow-up (p = 0.031). CONCLUSIONS: Chemotherapy had a beneficial effect on the performance status of the patients. No significant changes in BMI or 6MWD were found during the study period, which might suggest the maintenance of the physical condition of the patients.

Adult , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma/drug therapy , Body Mass Index , Carcinoma, Non-Small-Cell Lung/drug therapy , Exercise Tolerance/physiology , Lung Neoplasms/drug therapy , Walking/physiology , Adenocarcinoma/physiopathology , Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Non-Small-Cell Lung/physiopathology , Exercise Tolerance/drug effects , Lung Neoplasms/physiopathology , Paclitaxel/therapeutic use , Platinum Compounds/therapeutic use
Acta cir. bras ; 25(2): 176-180, Mar.-Apr. 2010. ilus, graf, tab
Article in English | LILACS | ID: lil-540494


Purpose: To verify the copaiba balsam (Copaifera officinalis) effect on Walker 256 carcinoma inoculated into vagina and uterine cervix of rats. Methods: Eighteen female Wistar rats weighing between 180-250g were used, distributed into 2 groups (GCop, GC). On the 1st day of the experiment, 0.3 ml of Walker 256 carcinoma (2x10(6) concentration) was inoculated in both groups; on the 3rd day of the experiment, it was given 4.8 ml/kg of distilled water to the GC group, and 4.8 ml/kg of copaiba balsam to the GCop group. On the 12th day, euthanasia was performed and the tumor was grafted, being weighted and verified its volume. The data were submitted to statistical analysis with ANOVA test. Results: It was observed that copaiba balsam presented a negative inhibitory potential of 70 percent. Conclusion: The copaiba balsam stimulated the tumor growth.

Objetivo: Verificar o efeito do óleo de copaíba da espécie Copaifera officinalis no carcinoma de Walker 256 inoculado em vagina e colo de útero de ratas. Métodos: Foram utilizadas 18 ratas da linhagem Wistar, pesando entre 180-250g, distribuídas em dois grupos (CCop, GC). No 1º dia de experimento, em ambos os grupos foi inoculado 0,3ml de tumor de Walker 256 na concentração de 2x10(6); no 3º dia após essa inoculação, foi iniciada a administração de água destilada na dose de 4,8 ml/kg ao GC, e copaíba na dose de 4,8 ml/kg ao GCop. No 12º dia foi realizada a eutanásia das ratas e ressecado o tumor, sendo este pesado e averiguado seu volume. Os dados obtidos foram submetidos à análise estatística pelo método ANOVA. Resultados: Observou-se que o óleo de copaíba apresentou um potencial inibitório negativo de 70 por cento. Conclusão: O óleo de copaíba estimulou o crescimento tumoral.

Animals , Female , Rats , Antineoplastic Agents, Phytogenic/therapeutic use , Balsams/therapeutic use , /drug therapy , Phytotherapy , Uterine Cervical Neoplasms/drug therapy , Vaginal Neoplasms/drug therapy , /pathology , Drug Screening Assays, Antitumor/methods , Rats, Wistar , Uterine Cervical Neoplasms/pathology , Vaginal Neoplasms/pathology
Article in English | WPRIM | ID: wpr-12975


The prognosis of patients with end-stage renal disease has improved with advances in hemodialysis techniques. However, many patients who undergo hemodialysis suffer from various types of cancer. Limited data is available to guide clinical management of these patients who may have impaired renal function. Here, we report our experience with the use of irinotecan for the treatment of a hemodialysis patient with small-cell lung cancer and end-stage renal disease.

Humans , Male , Middle Aged , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/analogs & derivatives , DNA Topoisomerases, Type I/antagonists & inhibitors , Disease-Free Survival , Follow-Up Studies , Kidney Failure, Chronic/complications , Lung Neoplasms/complications , Renal Dialysis/methods , Small Cell Lung Carcinoma/complications
Rev. para. med ; 22(2): 17-22, abr.-jun. 2008. ilus, tab
Article in English | LILACS | ID: lil-521076


Objective: to evaluate the antineoplasic effect of ethanolic extract of the vine of Uncaria tomentosa (cat:.. claw) on cell viability and survivorship of Ehr/ich tumor-bearing mice. Methods: 2,8x107 Ehr/ich tumor cells were inoculated in the peritoneum of 30 Swiss male mice distributed on 3 groups of 10 animals, which were observed for 30 days and received the following solutions by gavage : CGcontrol group, which received NaCl 0,9%; EG 100 - experimental group that received the ethano/ic extract on a 100 mg/Kg dosage; and EG 200 - experimental group that received the ethano/ic extract on a 200 mg/Kg dosage. After eleven days oftreatment, 1ml of ascitic liquid was withdrawn of each animal and cellular counting was made on a Neubauer chamber by optic microscopy using the Trypan blue stain. Results: there were reduction on tumor proliferation on EG 100 and 200 of 39 and 43,5%, respectively, and a slightly increase on survivorship of EG 100 compared to control gro/lp. Conc/usion: the ethanolic extract of the vine of Uncaria tomentosa had a statistically significant and dose-dependant anti-proliferative action on Ehrlich tumor. However, on the dosages and routes studied, there was no significant increase on survi vorship of the animais.

Objetivo: avaliar os efeitos antineoplásicos do extrato etanólico (EA) do cipó de Uncaria tomentosa (Unha de gato) sobre a viabilidade celular e sobrevida de camundongos portadores do Tumor Ascítico de Ehrlich (TA E). Método: inoculadas 2,8 x 107 células do TA E, por via intraperitoneal, em 30 camundongos suíços, machos, distribuídos e.m três grupos de dez animais cada, sendo observados por 30 dias e recebendo as seguintes soluções por gavagem, por onze dias, após a inoculação do tumor: GC - GrttpO controle, que recebeu solução salina de NaCl a 0,9%; GE 100 - Grupo experimental que recebeu o EA na dose de 100 mglKg; e GE 200 - Grupo experimental, que recebeu o EA na dose de 200 mglKg. Após onze dias de tratamento, foi retirado 1 ml de líquido ascítico de cada animal e feita a contagem celular sob microscopia óptica em câmara de Neubauer, utilizando a coloração de azul de Trypan. Resultados: Houve redução na proliferação do tumor dos animais dos grupos GE 100 e GE 200 da ordem de 39 e 43,5%, respectivamente, e um ligeiro aumento da sobrevida dos animais do grupo GE /00 em cerca de três dias, comparado ao grupo controle. Conclusão: o extrato alcoólico do cipó de Uncaria tomentosa exerceu ação antiproliferativa do TA E, de forma estatisticamente significativa e dose dependente. Porém, nas doses e vias mencionadas o extrato não aumentou de forma significativa a sobrevida dos animais.

Animals , Mice , Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Ehrlich Tumor/drug therapy , Plant Extracts/therapeutic use , Phytotherapy , Plants, Medicinal , Cat's Claw
Indian Heart J ; 2008 May-Jun; 60(3): 195-9
Article in English | IMSEAR | ID: sea-5254


OBJECTIVE: Bypass surgery remains the revascularization strategy of choice for left main trunk coronary artery disease in an unselected group of patients. Drug eluting stents have been proposed as a viable alternative to bypass surgery for left main trunk lesions but their intermediate and long term outcomes are still under scrutiny. METHODS: A series of 50 patients with significant unprotected left main trunk stenosis (>50%) underwent revascularization with drug eluting stents (sirolimus and paclitaxel stents) and were enrolled in a registry. Follow up angiography was clinically driven. Recurrent chest pain and ischemia on myocardial perfusion imaging were clinical parameters that mandated repeat angiography. Prespecified primary endpoints of this registry were defined as major adverse cardiac event at 2 year follow up. RESULTS: No differences in outcomes were noted with either type of drug eluting stent used in this study (Sirolimus versus Paclitaxel). The low major adverse cardiac event rate of 14% at 2 years warrants a randomized control trial in a low surgical risk group of patients comparing bypass grafting with left main trunk percutaneous intervention. CONCLUSION: This registry confirms findings by other investigators about the safety of unprotected LMT stenting in an unselected group of patients. The acceptable MACE rate at 2 years from registries such as this suggests the need for a randomized control trial comparing the two strategies.

Aged , Angioplasty, Balloon, Coronary , Antineoplastic Agents, Phytogenic/therapeutic use , Coronary Artery Bypass , Coronary Artery Disease/drug therapy , Coronary Restenosis/drug therapy , Coronary Vessels/pathology , Drug-Eluting Stents , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Paclitaxel/therapeutic use , Registries , Sirolimus/therapeutic use , Time Factors