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1.
Arq. bras. cardiol ; 117(6): 1147-1158, dez. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1350045

ABSTRACT

Resumo Fundamento A doxorrubicina (DOX) é frequentemente usada para tratar muitos tipos de cânceres, apesar da cardiotoxicidade dose-dependente. Como alternativa, o resveratrol é um polifenol que tem demonstrado efeitos cardioprotetores em vários modelos de disfunção cardíaca. Objetivo Este estudo investigou se o tratamento com resveratrol em ratas gestantes protege contra toxicidade induzida por doxorrubicina em cardiomiócitos da ninhada. Métodos Ratas Wistar (n-8) receberam sresveratrol como suplemento alimentar durante a gestação. No nascimento da ninhada, os corações (9-11) foram usados para se obter a cultura primária de cardiomiócitos. A cardiotoxicidade induzida por DOX e os efeitos da suplementação com resveratrol foram avaliados por marcadores de stress oxidativo, tais como oxidação da diclorofluoresceína diacetato, diminuição da atividade de enzimas antioxidantes, e oxidação do teor total de grupos sulfidrila, além da avaliação da viabilidade celular, geração de danos ao DNA, bem como a resposta de reparo aos danos ao DNA. Um valor de p <0,05 foi considerado estatisticamente significativo. Resultados Os cardiomiócitos de neonatos de ratas que receberam suplemento resveratrol apresentaram um aumento (p <0,01) na viabilidade das células, e diminuição (p <0,0001) de células apoptóticas/necróticas após o tratamento com DOX, o que está correlacionado às atividades de enzimas antioxidantes e produção de diclorofluoresceína. Além disso, o resveratrol protegeu os cardiomiócitos de danos ao DNA induzidos por DOX, apresentando uma diminuição (p <0,05) nas quebras de DNA induzidas por stress oxidativo, avaliadas pela atividade de enzimas reparadoras do DNA endonuclease III e formamidopirimidina glicosilase. A suplementação com resveratrol aumentou (p <0,05) a expressão da proteína reparadora Sirt6 nos cardiomiócitos dos filhotes. Conclusão Essa pesquisa indica que a suplementação com resveratrol durante o período gestacional tem um efeito cardioprotetor no coração da ninhada contra a toxicidade induzida por DOX, o que pode se dever a sua função antioxidante, e o aumento na resposta de danos ao DNA.


Abstract Background Doxorubicin (DOX) is frequently used to treat many types of cancers, despite its dose-dependent cardiotoxicity. Alternatively, resveratrol is a polyphenol that has shown useful cardioprotective effects in many heart dysfunction models. Objective This study investigated whether resveratrol treatment in pregnant rats protects against doxorubicin-induced toxicity in offspring cardiomyocytes. Methods Wistar rats (n=8) were supplemented with dietary resveratrol during pregnancy. Upon the offspring's birth, hearts (9-11) were used to obtain the primary culture of cardiomyocytes. DOX-induced cardiotoxicity and the effects of resveratrol supplementation were evaluated by oxidative stress markers, such as dichlorofluorescein diacetate oxidation, decrease in the activity of antioxidant enzymes, and oxidation of total sulfhydryl content, in addition to cell viability evaluation, DNA damage generation, and DNA damage repair response. A value of p<0.05 was considered statistically significant. Results Neonatal cardiomyocytes from resveratrol supplemented rats exhibiting an increase (p<0.01) in cell viability and lower (p<0.0001) apoptotic/necrotic cells after DOX treatment, which correlates with the activities of antioxidant enzymes and dichlorofluorescein production. Moreover, resveratrol protected cardiomyocytes from DOX-induced DNA damage, showing a decrease (p<0.05) in DNA breaks induced by oxidative stress, evaluated by the activity of DNA-repair enzymes endonuclease III and formamidopyrimidine glycosylase. Supplementation with resveratrol increased (p<0.05) the expression of the repair protein Sirt6 in the cardiomyocytes of the pups. Conclusion This research indicates that supplementation with resveratrol during the gestational period has a notable cardioprotective effect on the offspring's heart against DOX-induced toxicity, which may well be due to its antioxidant function, and the increase in the DNA damage repair response.


Subject(s)
Animals , Female , Pregnancy , Rats , Doxorubicin/toxicity , Myocytes, Cardiac , Rats, Wistar , Dietary Supplements , Resveratrol/pharmacology
2.
Rev. Ciênc. Méd. Biol. (Impr.) ; 20(2): 269-276, set 29, 2021. tab
Article in Portuguese | LILACS | ID: biblio-1354472

ABSTRACT

Introdução: a superexpressão da COX-2 relaciona-se com o aumento da produção de fatores de crescimento vascular e como consequência, com o desenvolvimento tumoral. O Firocoxib é um anti-inflamatório não esteroidal utilizado para inflamação associada à osteoartrite em cães. É o inibidor mais seletivo da COX-2, reduzindo eficientemente a ação desta enzima. Estudos indicam os benefícios do Firocoxib na terapia antineoplásica. Objetivo: este trabalho objetivou avaliar o efeito modulador do Firocoxib sobre a ação da doxorrubicina (DXR) por meio do teste de tumores epiteliais (ETT) em Drosophila melanogaster. Metodologia: foram preparadas três concentrações de Firocoxib: 2,5; 5 e 10 mg/mL, utilizadas isoladamente e em associação à doxorrubicina. O tratamento ocorreu com larvas de D. melanogaster descendentes do cruzamento de fêmeas wts/TM3 com machos mwh/mwh. Resultados: os resultados sugerem que o Firocoxib possui atividade moduladora sobre a ação carcinogênica da DXR, pois houve redução significativa nas frequências tumorais dos indivíduos tratados com diferentes concentrações de Firocoxib em cotratamento com a doxorrubicina quando comparadas à frequência tumoral do controle positivo. Conclusão: conclui-se que, nas presentes condições experimentais, o Firocoxib reduziu a frequência de tumores induzidos pela doxorrubicina em D. melanogaster.


Introduction: COX-2 overexpression is related to increased production of vascular growth factors and, as a consequence, to tumor development. Firocoxib is a non-steroidal anti-inflammatory drug used for inflammation associated with osteoarthritis in dogs. It is the most selective inhibitor of COX-2, efficiently reducing the action of this enzyme. Studies indicate the benefits of Firocoxib in anticancer therapy. Objective: this study aimed to evaluate the modulatory effect of Firocoxib on the action of doxorubicin (DXR) by means of the epithelial tumor test (ETT) in Drosophila melanogaster. Methodology: three concentrations of Firocoxib were prepared: 2.5; 5 and 10 mg/mL, used alone and in association with doxorubicin. The treatment occurred with D. melanogaster larvae descended from the crossing of wts/TM3 females with mwh/mwh males. Results: the results suggest that Firocoxib has modulating activity on the carcinogenic action of DXR, as there was a significant reduction in tumor frequencies in individuals treated with different concentrations of Firocoxib in co-treatment with doxorubicin when compared to the tumor frequency of the positive control. Conclusion: it is concluded that, under the present experimental conditions, Firocoxib reduced the frequency of tumors induced by doxorubicin in D. melanogaster.


Subject(s)
Animals , Doxorubicin , Drosophila melanogaster , Chemical Compounds , Evaluation Study
3.
Rev. venez. oncol ; 33(1): 40-45, mar. 2021. ilus
Article in Spanish | LILACS, LIVECS | ID: biblio-1147477

ABSTRACT

El linfoma de Burkitt es una neoplasia altamente agresiva y es un tipo raro de linfoma no Hodgkin localizado. Aunque los niños son los más frecuentemente afectados, en adultos ocurren principalmente durante el embarazo o el puerperio. La mama rara vez constituye la localización primaria del linfoma no Hodgkin. Se presenta un caso de linfoma de Burkitt primario de mama durante el embarazo. Paciente de 37 años con embarazo de 24 semanas quien presentó aumento de volumen difuso de mama derecha. La mama estaba aumentada de tamaño, dolorosa y homogénea con tumoración elástica y firme. La ecografía demostró inflamación difusa con tumoración heterogénea e hipoecoica con contornos ligeramente irregulares, marcadores tumorales estaban normales las pruebas serológicas fueron negativas. La biopsia de la lesión mostró tejido mamario reemplazado por células linfoideas de tamaño mediano con citoplasma basófilo y múltiples vacuolas. Estudios inmunohistoquímicos fueron positivos para el antígeno leucocitario común, CD10, CD20, CD43, Bcl-6. El análisis cromosómico reveló que más del 90 % de las células neoplásicas exhibieron translocación t llevando al diagnóstico final de linfoma de Burkitt de mama. Luego de evaluar las posibilidades terapéuticas y del consentimiento de la paciente se inició tratamiento citostático sistémico. Los linfomas primarios de mama son extremadamente raros. El linfoma de Burkitt primario de la mama es mucho menos común que los otros linfomas. Los métodos de clasificación, detección y tratamiento de esta afección siguen siendo objeto de debates e investigaciones(AU)


The Burkitt's lymphoma is a highly aggressive neoplasm and is a rare type of localized non-Hodgkin lymphoma. Although children are the most frequently affected, in adults they occur mainly during the pregnancy or the puerperium. The breast rarely constitutes the primary location for non-Hodgkin lymphoma. The study of a case of primary Burkitt lymphoma of the breast during pregnancy is presented. This is a 37 year old patient with a 24 week pregnancy who presented a diffuse increase in the volume of the right breast. The breast was enlarged, painful and homogeneous with a firm, elastic mass. The ultrasonography showed diffuse inflammation with a heterogeneous and hypoechoic tumor with slightly irregular contours. The tumor marker values were normal and the serological tests were negative. The biopsy of the lesion showed breast tissue replaced by medium-sized lymphoid cells with basophilic cytoplasm and multiple vacuoles. Immunohistochemically studies were positive for the common leukocyte antigen, CD10, CD20, CD43, Bcl-6. The chromosomal analysis revealed that more than 90 % of neoplastic cells exhibited t translocation leading to the final diagnosis of Burkitt lymphoma of the breast. After evaluating the therapeutic possibilities and the patient's consent, systemic cytostatic treatment was started. Primary breast lymphomas are extremely rare. The primary Burkitt lymphoma of the breast is much less common than other lymphomas. The methods of classification, detection, and the treatment of this condition continue to be the subject of debate and research(AU)


Subject(s)
Humans , Female , Adult , Lymphoma, Non-Hodgkin , Breast Neoplasms , Burkitt Lymphoma/physiopathology , Precursor Cells, B-Lymphoid , Vincristine/therapeutic use , Prednisone/therapeutic use , Doxorubicin/therapeutic use , Tomography, X-Ray Computed , Cyclophosphamide/therapeutic use , Rituximab/therapeutic use
4.
Arq. bras. med. vet. zootec. (Online) ; 73(2): 513-516, Mar.-Apr. 2021. graf
Article in English | LILACS, VETINDEX | ID: biblio-1248925

ABSTRACT

A doxorrubicina (dox) é um medicamento antineoplásico que induz cardiotoxicidade por estresse oxidativo. Os flavonoides são antioxidantes extraídos de plantas como Camellia sinensis e Arrabidaea chica (Fridericia chica). Esta pesquisa objetivou avaliar efeitos protetores do extrato de A. chica (AC), comparado ao de C. sinensis (CS), frente ao estresse oxidativo induzido pela dox, no coração. Cardiomiócitos e células neoplásicas MDA-MB 231 foram incubados com AC e CS. Depois, adicionou-se dox e avaliaram-se taxas de viabilidade e morte celular. A citometria de fluxo para o ensaio de iodeto de propídeo (IP) em cardiomiócitos mostrou as seguintes taxas de morte celular: controle 53%; dox 78% (maior que controle, P=0,015); AC_12,5µg/mL + dox 65% (menor que dox, P=0,031); AC_25µg/mL + dox 62% (menor que dox, P=0,028); AC_50µg/mL + dox 63% (menor que dox, P=0,030); CS_12,5µg/mL + dox 71% (menor que dox, P=0,040); CS_25µg/ml + dox 69% (menor que dox, P=0,037); CS_50µg/mL + dox 74% (menor que dox, P=0,044). Resultados das células MDA-MB 231 mostraram que nenhum extrato interferiu na atividade antitumoral da dox. Os dados de IP foram corroborados pelos de MTT. Este estudo reporta promissora utilização de A. chica na prevenção da cardiotoxicidade induzida pela dox.(AU)


Subject(s)
Animals , Rats , Plant Extracts/therapeutic use , Doxorubicin , Bignoniaceae/chemistry , Cardiotoxicity/therapy , Cardiotoxicity/veterinary , Plants, Medicinal , Flavonoids/therapeutic use
7.
Journal of Experimental Hematology ; (6): 1136-1140, 2021.
Article in Chinese | WPRIM | ID: wpr-888529

ABSTRACT

OBJECTIVE@#To evaluate the efficacy and safety of CHOP regimen based on doxorubicin hydrochloride liposome in the initial treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#Thirty-one patients with DLBCL treated from January 1, 2012 to December 31, 2019 were analyzed retrospectively, their median age was 83 (71-95) years old, and all of them were in Ⅲ-Ⅳ stage, including 17 cases who had international prognostic index (IPI) ≥ 3. The patients were treated with R-CHOP and CHOP regimens based on doxorubicin hydrochloride liposome. The efficacy and safety were evaluated during and after treatment.@*RESULTS@#A total of 219 chemotherapy cycles and 7 median cycles were performed in 31 patients. The overall response (OR) rate and complete remission (CR) rate was 80.7% (25/31) and 61.3% (19/31), respectively, as well as 2 cases (6.5%) stable, 4 cases (12.9%) progressive. The main toxicities were as follows: the incidence of grade Ⅲ -Ⅳ neutropenia was 29% (9/31); two patients (6.5%) developed degree Ⅰ-Ⅱ cardiac events, which were characterized by new degree Ⅰ atrioventricular block; there were no cardiac events requiring emergency treatment and discontinuation of chemotherapy. The 1-year, 2-year and 3-year overall survival rate was 83.9%, 77.4% and 61.3%, respectively. The 1-year, 2-year and 3-year progression-free survival rate was 77.4%, 64.5% and 61.3%, respectively.@*CONCLUSION@#The chemotherapy regimen based on doxorubicin hydrochloride liposome has better efficacy and higher cardiac safety for elderly patients with DLBCL.


Subject(s)
Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Humans , Liposomes/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prednisolone , Prednisone/therapeutic use , Retrospective Studies , Rituximab/therapeutic use , Vincristine/therapeutic use
8.
Journal of Experimental Hematology ; (6): 1797-1801, 2021.
Article in Chinese | WPRIM | ID: wpr-922337

ABSTRACT

OBJECTIVE@#To compare the treatment outcome and prognosis of the newly-treated myc@*METHODS@#152 double-expression lymphoma patients (myc@*RESULTS@#The median age of 152 DEL patients was 60.5 years old (15-87 years old). 85 patients (55.9%) were Ann Arbor stage III/IV. There was no significant difference in clinical data between the patients in the two groups. Multivariate Cox regression analysis showed that bcl-6 expression, ECOG score, and stage were the independent prognostic factors for the entire group of DEL patients. There was no statistical difference in ORR between the patients in the two groups (χ2=0.749, P=0.387). Kaplan-Meier survival analysis showed that PFS and OS of the bcl-6@*CONCLUSION@#bcl-6


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Middle Aged , Prednisolone , Prognosis , Vincristine/therapeutic use , Young Adult
9.
Article in Chinese | WPRIM | ID: wpr-879054

ABSTRACT

This study is to observe whether platycodin D has the guiding role in treatment of mouse lung cancer with doxorubicin and explore its guiding mechanism. In vitro, platycodin D and doxorubicin(alone or in combination) were added into Lewis lung cancer(LLC) cells to detect the cell proliferation and doxorubicin uptake. Cell morphological changes were analyzed by cell holographic analysis system; cell gap junctional intercellular communication(GJIC) was tested by fluorescent yellow tracer; lyso-tracker red was used to examine lysosomal function; LC-3 B(Light chain 3 beta)and P62(heat shock 90-like protein)staining were used to test auto-phagy and autophagic degradation respectively; and P-glycoprotein(P-gp) expression was examined by Western blot. In vivo, lung solid tumor was formed in mouse LLC cells via intravenous injection. Platycodin D and doxorubicin(alone or in combination) were used to treat tumor-bearing mice for four weeks, and then the tumor size was examined, mouse survival time was recorded, doxorubicin uptake in lung tissues was tested, and lung tissues were stained for observation by HE(hematoxylin-eosin) and immunohistochemistry. The results showed that platycodin D at the experimental concentration had no effect on LLC cell proliferation but decreased LLC cell volume, promoted the cells to uptake doxorubicin and enhanced the inhibitory action of doxorubicin on cell proliferation. Platycodin D could promote GJIC and lysosomal function, increase autophagy and autophagic degradation and suppress P-gp expression. Platycodin D at the experimental dose in this study had no effect on LLC lung solid tumors in mice, increased doxorubicin uptake in lung tissues and enhanced the therapeutic efficacy of doxorubicin on lung solid tumors. Platycodin D could improve the extracellular matrix deposition in lung solid tumors, decreased the lung mucin 5 AC secretion and pulmonary vessel permeability. In summary, platycodin D had the guiding role in treating mouse lung cancer with doxorubicin, and its guiding mechanism may be associated with the promotion of cell communication, lysosomal function, and improvement of extracellular environment.


Subject(s)
Animals , Cell Line, Tumor , Doxorubicin , Lung Neoplasms/drug therapy , Mice , Saponins , Triterpenes
10.
Braz. j. biol ; 81(2): 268-277, 2021. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1153357

ABSTRACT

This study evaluated the genotoxicity of lyophilized glycolic extract of Theobroma cacao Linné seeds (TCL), using the micronucleus assay in bone marrow of mice. The interaction between TCL and doxorubicin (DXR) was also analyzed. Experimental groups were evaluated 24-48 h after treatment with N-Nitroso-N-ethylurea (NEU: 50 mg/kg), DXR (5 mg/kg), NaCl (145 mM), TCL (0.5-2 g/kg), and TCL (2 g/kg) in combination with DXR (antigenotoxic assays). Analysis of micronucleated polychromatic erythrocytes (MNPCEs) showed no significant differences between all the treatment doses of TCL and NaCl control. Mice experimentally treated with DXR and NEU significantly induced MNPCEs. However, a significant reduction of MNPCEs was also observed when TCL was administered in combination with the chemotherapeutic agent DXR. The analysis of the PCE/NCE ratio revealed no significant differences between the NaCl control, all doses of TCL, and DXR. However, there were significant differences in the PCE/NCE ratio between positive NEU control and all other treatments. The PCE/NCE ratio observed after treatment with TCL and DXR showed significant differences and intermediate values to controls (NaCl and NEU). This study suggests absence of genotoxicity and cytotoxicity of TCL, regardless of dose, sex, and time. TCL reduced genotoxic effects induced by DXR, suggesting potential antigenotoxic effects.


Este estudo avaliou a genotoxicidade do extrato glicólico liofilizado de sementes de Theobroma cacao Linné (TCL), usando o ensaio do micronúcleo em medula óssea de camundongos. A interação entre TCL e doxorrubicina (DXR) foi também analisada. Grupos experimentais foram avaliados 24-48 h após tratamento com N-Nitroso-N-etilureia (NEU: 50 mg/kg), DXR (5 mg/kg), NaCl (145 mM), TCL (0,5-2 g/kg), e TCL (2 g/kg) em combinação com DXR (ensaio antigenotóxico). As análises de eritrócitos policromáticos micronucleados (EPCMNs) não mostraram diferenças significantes entre todas as doses de tratamento do TCL e o controle NaCl. Camundongos experimentalmente tratados com DXR e NEU induziram significativamente EPCMNs. Contudo, uma redução significante de EPCMNs foi também observada quando TCL foi administrada em combinação com o agente quimioterapêutico DXR. As análises da relação EPC/ENC (eritrócito policromático/eritrócito normocromático) revelaram ausência de diferenças significantes entre o controle NaCl, todas as doses de TCL e DXR. Contudo, houve diferenças significantes na relação EPC/ENC entre o controle positivo NEU e todos os outros tratamento. A relação ECP/ENC observada após o tratamento com TCL e DXR mostrou diferenças significantes e valores intermediários aos controles (NaCl e NEU). Este estudo sugere ausência de genotoxicidade e citotoxicidade de TCL, independentemente da dose, sexo e tempo. TCL reduziu os efeitos genotóxicos induzidos por DXR, sugerindo potencial efeitos antigenotóxicos.


Subject(s)
Animals , Mice , DNA Damage , Cacao/toxicity , Cytotoxins/analysis , Plant Extracts/pharmacology , Micronucleus Tests , Doxorubicin , Erythrocytes
11.
Chinese Journal of Biotechnology ; (12): 2522-2533, 2021.
Article in Chinese | WPRIM | ID: wpr-887818

ABSTRACT

To explore the immunomodulatory effect of adriamycin on 4T1 breast cancer. We used a tandem mass tag-based quantitative proteomic method to detect differential proteins in breast cancer tissues, and multiple bioinformatics databases to analyze the differentially expressed proteins in the proteome. Also, we used enzyme-linked immunosorbent assay to detect the effects of adriamycin on helper T cells 1 and 2 in breast cancer tissues, and flow cytometry to detect CD4+ T cells, CD8+ T cells and regulatory T cells. We discovered the immunomodulatory targets of adriamycin in differential proteins. In total 170 differential proteins were significantly up-regulated, whereas 58 were markedly down-regulated. In addition, 73 proteins were involved in immune regulation. Kyoto encyclopedia of genes and genomes enriched important protein pathways related to cytokines and factor receptors, interleukin 17 pathway and cancer transcriptional regulatory pathways. These pathways and important differential proteins related to immunomodulatory functions were ultimately regulated by adriamycin on CD4+ T cells, CD8+ T cells and regulatory T cells, thereby affecting the prognosis of breast cancer. Moreover, adriamycin significantly increased interleukin 2, CD4+ T and CD8+ T (P<0.01) and markedly reduced regulatory T cells (P<0.05). The function of adriamycin against triple-negative breast cancer was closely related to the immunoregulation process of the differential proteins Ighm, Igkc, S100A8, S100A9 and Tmsb4x. Adriamycin could regulate the content of helper T cells 1 cytokines, CD4+ T and CD8+ T lymphocytes in breast cancer and reduce the number of regulatory T cells to produce immunomodulatory effects.


Subject(s)
Animals , Breast Neoplasms/drug therapy , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Disease Models, Animal , Doxorubicin/pharmacology , Female , Humans , Mice , Proteomics
12.
Arq. bras. cardiol ; 115(5): 885-893, nov. 2020. tab, graf
Article in Portuguese | SES-SP, LILACS, SES-SP | ID: biblio-1142279

ABSTRACT

Resumo Fundamento: A cardiotoxicidade pode ser uma consequência do tratamento com doxorrubicina (DOX). Objetivos: Verificar o efeito do exercício aeróbio na prevenção da disfunção cardíaca de murinos expostos à DOX. Método: Uma busca abrangente foi realizada em nove bases de dados, em dezembro de 2017. Estudos que avaliaram a função cardíaca de murinos expostos à DOX foram incluídos. O nível de significância adotado foi de 5%. Resultados: Na comparação entre 230 murinos submetidos a exercício aeróbio mais DOX e 222 controles (tratados somente com DOX), a fração de encurtamento mostrou uma melhora de 5,33% a favor do grupo experimental (p = 0,0001). A pressão desenvolvida no ventrículo esquerdo também mostrou um aumento de 24,84 mmHg a favor do grupo de 153 murinos que realizaram exercício em comparação com o grupo controle de 166 murinos (p = 0,00001). Conclusão: Estudos pré-clínicos incluídos nesta metanálise indicaram que o exercício é uma boa estratégia não farmacológica para preservar a função cardíaca pós-DOX.


Abstract Background: Cardiotoxicity may be a consequence of treatments with doxorubicin (DOX). Objectives: To investigate the effect of aerobic exercise on the prevention of cardiac dysfunction in murines exposed to DOX. Method: A comprehensive search was conducted in 9 databases in December 2017. Studies that evaluated the cardiac function of murines exposed to DOX were included. The significance level adopted was 5%. Results: In a comparison between 230 murines that underwent aerobic exercise plus DOX treatment and 222 control murines (DOX treatment only), fractional shortening showed an improvement of 5.33% in favor of the experimental group (p = 0.00001). Left ventricle developed pressure also showed an increase of 24.84 mm Hg in favor of the group of 153 murines that performed exercise in comparison to the control group of 166 murines (p = 0.00001). Conclusion: Preclinical studies included in this meta-analysis indicated that exercise is a good nonpharmacological strategy for preserving post-DOX cardiac function.


Subject(s)
Animals , Rats , Physical Conditioning, Animal , Heart Diseases , Exercise , Doxorubicin/adverse effects , Cardiotoxicity/etiology , Antibiotics, Antineoplastic
14.
Oncol. (Guayaquil) ; 30(2): 149-158, 31 de agosto del 2020.
Article in Spanish | LILACS | ID: biblio-1145226

ABSTRACT

Introducción: Los esquemas de quimioterapia en el tratamiento de cáncer de mama incluyen Antraciclinas con una efectividad de respuesta alta, sin embargo en algunos casos el potencial efecto terapéutico se ve limitado por la Cardiomiopatía Inducida por Antraciclinas (CIPA).El objetivo del estudio fue establecer la prevalencia longitudinal de esta entidad. Métodos:Este estudiolongitudinalfue realizado en el Instituto Oncológico Nacional "Dr.Juan Tanca Marengo" -SOLCA-Guayaquil. El período de exposición fue abril a diciembredel 2008,laobservación terminó enjunio 2020.Seincluyó mujeres con cáncer de mama, en tratamiento con antraciclinas, clasificadas por riesgo Cardiovascular de Framingham Bajo (A), moderado (B) y alto (C).Se midió lasalteraciones electrocardiográficas (AEKG) basales, a las 6 y 24 horas.Desarrollo de CIPA en seguimiento a 12 años.La muestra fue no probabilística tipo censo. Se utiliza estadística descriptivacon Intervalo de confianza para proporciones. Resultados: Ingresaron al estudio 50 casos son AEKG. El desarrollo de AEKG a 6 horas en 18/50 casos (36% IC95% 34.1-37.9%), estas AEKG persistieron hasta las 24 horas. Las AEKG se presentaron en un 18.5% en mujeres con Riesgo A, 52.4% enRiesgo B y 100%en Riesgo C. El desarrollo de CIPA a12 años fue de 3.6% (2.3-4.9%) en CIPA-Subaguda y de 7.1% (5.3-9.0%)en CIPA crónica. CIPA Subaguda+ crónica 10.7% (8.6-12.9%). Conclusiones: los eventos de cardiotoxicidad aguda fueron detectados por AEKG,en el seguimiento a largo plazo laCIPAsedesarrollóen un porcentaje un poco mayor a la literatura reportada.


Introduction:Chemotherapy regimens in the treatment of breast cancer include Anthracyclines with a high response effectiveness, however in some cases the potential therapeutic effect is limited by Anthracycline Induced Cardiomyopathy (CIPA). The objective of the study was to establish the longitudinal prevalence of this entity. Methods: This longitudinal, observational study was conducted at the National Oncological Institute "Dr. Juan Tanca Marengo "-SOLCA-Guayaquil. The exposure period was April to December 2008. The observation period ended on June 30, 2020. It included women> 18 years with breast cancer, treated with anthracyclines, classified by Framingham Cardiovascular Risk as Low Risk (A) , moderate risk (B) and high risk (C). Electrocardiographic abnormalities (AEKG) were measured at baseline, at 6 hours and at 24 hours and development of CIPA at 12-yearfollow-up. The sample was non-probabilistic, census type. Descriptive statistics with confidence interval for proportions are used. Results: Fifty cases entered the study are AEKG. The development of AEKG at 6 hours in 18/50 cases (36% 95% CI 34.1-37.9%),these AEKG persisted until 24 hours. AEKG were presented in 18.52% in women with Risk A, 52.38% in Risk B and 100% in Risk C. The development of CIPA at 12 years was 3.57% (2.27-4.87%) in CIPA-Subacute and 7.14 % (5.34-8.95% in chronic CIPA. Subacute + chronic CIPA 10.71% (8.55-12.88%). Conclusions: In this study it is concluded that acute cardiotoxicity events were detected by electrocardiographic changes and that in the long-term follow-up they were evident in a slightly higher percentage than that reported in the international literature.


Subject(s)
Humans , Stroke Volume , Anthracyclines , Cardiomyopathies , Breast Neoplasms , Doxorubicin , Electrocardiography
15.
Article in English | WPRIM | ID: wpr-880597

ABSTRACT

OBJECTIVES@#To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM.@*METHODS@#The K562 and K562/ADM cells were respectively treated with ADM and idelalisib at different concentrations. The 50% inhibitory concentration (IC@*RESULTS@#The cell survival rates were significantly decreased in a dose-dependent manner when the cells were treated with different doses of ADM (0.001-10.000 mg/L ). The IC@*CONCLUSIONS@#Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Cell Proliferation , Doxorubicin/pharmacology , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , K562 Cells , Leukemia, Myeloid , Purines , Quinazolinones
16.
Journal of Experimental Hematology ; (6): 1919-1922, 2020.
Article in Chinese | WPRIM | ID: wpr-879993

ABSTRACT

OBJECTIVE@#To summarize and analyze the clinical characteristics, treatment and prognosis of acute lung injury in patients with diffuse large B-cell lymphoma (DLBCL) after chemotherapy with rituximab chemotherapy, so as to improve the understanding of the disease and guide the clinical treatment.@*METHODS@#Twenty-Six patients with DLBCL were treated with rituximab chemotherapy and developed to acute lung injury in Third Hospital of Peking University from January 2013 to September 2018 were selected. The clinical features, imaging findings, chemotherapy course, therapeutic effect and prognosis were analyzed.@*RESULTS@#The main clinical symptoms of patients were fever, cough and chest tightness, among which 12 patients showed hypoxia and 3 patients showed respiratory failure type I. The mainly manifested chest CT was diffusive glass grinding in both lungs, and some patients were complicated with a small amount of pleural effusion. The onset chemotherapy time was mainly distributed in 2 to 4 courses, the time between the onset of symptoms and the infusion of rituximab was 8 to 49 days. 25 patients shows no obvious limitation in daily life after effective treatment, and 1 patient died of ineffective treatment.@*CONCLUSION@#There are no typical clinical symptoms in the early stage of acute lung injury after rituximab chemotherapy in DLBCL. Early detection and early hormone therapy are very important to achieve good therapeutic effect.


Subject(s)
Acute Lung Injury , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prognosis , Rituximab/therapeutic use , Treatment Outcome , Vincristine/therapeutic use
17.
Journal of Experimental Hematology ; (6): 1912-1918, 2020.
Article in Chinese | WPRIM | ID: wpr-879992

ABSTRACT

OBJECTIVE@#To analyze the efficacy of rituximab combined with CHOP/EPOCH regimen for treatment of diffuse large B-cell lymphoma(DLBCL) patients, and to explore the high risk factors of refractory and relapsed patients.@*METHODS@#The clinical data of 72 patients with de novo DLBCL from December 2012 to December 2018 in the Department of Hematology, Zhongda Hospital Affiliated to Southeast University were retrospectively analyzed. The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH was analyzed, and survival analysis was conducted to explore the risk factors influencing refractory recurrence.@*RESULTS@#45 cases among 72 patients achieved complete remission (CR), 11 cases achieved partial remission (PR), the total remission rate was 77.78%. 25 cases (34.2%) refractory and relapsed. Single factor analysis showed that the B symptoms, low Hb, high NLR, low MLR, high β@*CONCLUSION@#The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH regimen is high, but about one third of the patients still show refractory and relapsed. B Symptoms, anemia, high β


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Etoposide , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Neoplasm Recurrence, Local , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Rituximab/therapeutic use , Treatment Outcome , Vincristine
18.
Chinese Journal of Oncology ; (12): 617-623, 2020.
Article in Chinese | WPRIM | ID: wpr-826582

ABSTRACT

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.


Subject(s)
Antibiotics, Antineoplastic , Therapeutic Uses , Consensus , Doxorubicin , Therapeutic Uses , Drug-Related Side Effects and Adverse Reactions , Female , Hand-Foot Syndrome , Humans , Neoplasms , Drug Therapy , Polyethylene Glycols , Therapeutic Uses , Practice Guidelines as Topic , Stomatitis
19.
Article in Chinese | WPRIM | ID: wpr-829046

ABSTRACT

OBJECTIVE@#To investigate the effect of Bmi-1 gene silencing on drug resistance of leukemia cell K562/ADR and to explore its possible mechanism.@*METHODS@#After two sequences of Bmi-1-siRNA were transfected into drug-resistant K562/ADR cells, the mRNA and protein expressions of Bmi-1 gene were detected. After Bmi-1 gene silencing the expression of P-gp and MDR1 were detected and the accumulation of doxorubicin in K562/ADR cells were detected by flow cytometry to determine the effect of Bmi-1 gene silencing on drug resistance of K562/ADR cells. The protein expression of NF-κB was analyzed after Bmi-1 gene silencing. Then after K562/ADR cells were treated with NF-κB inhibitor PDTC, the protein expression of P-gp and its functional changes were analyzed to determine the effect of NF-κB on drug resistance of leukemia cells. The protein expressions of PTEN, AKT and p-AKT after Bmi-1 gene silencing were detected and the effect of Bmi-1 gene silencing on PTEN/PI3K/AKT signaling pathway in drug-resistant cells was determined. After K562/ADR cells were treated with PI3K/AKT pathway inhibitor LY294002, the protein expressions of NF-κB and P-gp were analyzed to determine the regulation of AKT on the expression of NF-κB and P-gp. The protein expressions of AKT, p-AKT, NF-κB and P-gp were detected after the Bmi-1-siRNA transfected cells were treated by PTEN inhibitor BPV. Above-mentioned expression of mRNA was detected by RT-PCR, and the protein expression was detected by Western blot.@*RESULTS@#The expression of Bmi-1 gene in K562/ADR cells decreased at both mRNA and protein levels and the doxorubicin accumulation increased after Bmi-1 gene silencing. The expression of MDR1/P-gp in Bmi-1-siRNA transfected cells was lower than that in K562/ADR cells (P<0.05). After Bmi-1 gene silencing, the activity of NF-κB decreased. The activity of NF-κB and P-gp expression was inhibited and the function of P-gp in K562/ADR cells was reduced by using NF-κB inhibitor (PDTC). The protein expression of PTEN increased while the protein expression of p-AKT decreased after Bmi-1 gene silencing (P<0.05). The protein expressions of p-AKT, P-gp and the activity of NF-κB were inhibited significantly by using PI3K/AKT inhibitor LY294002 (P<0.05). After the Bmi-1-siRNA transfected cells were treated by PTEN inhibitor BPV, the activity of NF-κB and the protein expressions of P-gp were restored.@*CONCLUSION@#Bmi-1 plays a key role in MDR-mediated multidrug resistance in K562/ADR cells, which may be mediated by activating PTEN/AKT pathway to regulate NF-κB.


Subject(s)
Doxorubicin , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , K562 Cells , Mitogen-Activated Protein Kinase 7
20.
Article in Chinese | WPRIM | ID: wpr-828535

ABSTRACT

Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.


Subject(s)
Antineoplastic Agents , Doxorubicin , Drug Delivery Systems , Gene Transfer Techniques , Humans , Mesenchymal Stem Cells , Neoplasms , Therapeutics , Paclitaxel , Research
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