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Int. j. morphol ; 42(1): 40-45, feb. 2024. ilus, tab
Article in English | LILACS | ID: biblio-1528826


SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.

La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.

Humans , Angiogenesis Inhibitors/therapeutic use , Celecoxib/therapeutic use , Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Cyclooxygenase 2 Inhibitors , Neoplasms/pathology , Antineoplastic Agents/therapeutic use
Chinese journal of integrative medicine ; (12): 62-74, 2024.
Article in English | WPRIM | ID: wpr-1010326


Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".

Humans , Retrospective Studies , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Sesquiterpenes/therapeutic use
Rev. Hosp. Ital. B. Aires (En línea) ; 43(4): 214-218, dic. 2023.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1537605


La amiloidosis AL es una enfermedad debida al depósito, en órganos y tejidos, de fibrillas formadas por cadenas livianas producidas de forma patológica por plasmocitos clonales. Su tratamiento actualmente está orientado a erradicar el clon de células plasmáticas; este históricamente se extrapoló de tratamientos disponibles y estudiados para otras discrasias sanguíneas. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA) confeccionó distintas guías de práctica clínica para el tratamiento de la amiloidosis AL. Desde entonces se han publicado ensayos clínicos que arrojan contundencia al conocimiento disponible hasta el momento, y están en desarrollo nuevas líneas de investigación que robustecen y estimulan el estudio en el área. En esta revisión se realiza una actualización de las guías existentes en lo que respecta al tratamiento de la amiloidosis por cadenas livianas.Como evidencia de relevancia, en el último año estuvieron disponibles resultados de ensayos clínicos que respaldan el uso de esquemas basados en daratumumab (un anticuerpo monoclonal anti-CD38+) para pacientes con diagnóstico reciente de amiloidosis AL como primera línea. Además, para el tratamiento de la amiloidosis AL refractaria o recaída, la disponibilidad de bibliografía respaldatoria es escasa y extrapolada del tratamiento del mieloma múltiple; sin embargo, actualmente existe evidencia de calidad para recomendar el uso de ixazomib, un inhibidor de proteosoma reversible por vía oral disponible en la Argentina desde 2020. Por último, se mencionan algunas líneas de investigación con otros anticuerpos monoclonales y terapéuticas basadas en el uso de CAR-T cells. (AU)

AL amyloidosis is a disease caused by the deposit in different organs and tissues of protein fibrils formed by light chains synthetized by pathological clonal plasma cells. Its treatment is currently aimed at eradicating this plasma cell clone and it has been historically extrapolated from available and validated treatments for other blood dyscrasias. In 2020, the Amyloidosis Study Group prepared different clinical practice guidelines for the treatment of AL amyloidosis.Since then, clinical trials have been published that confirm and strengthen the knowledge available up to now, and new lines of research are being developed that stimulate study in the area. In this review, an update of the existing guidelines regarding the treatment of AL amyloidosis is made. As relevant evidence, in the last year, results of clinical trials have been made available that support the use of regimens based on Daratumumab (an anti-CD38+ monoclonal antibody) for patients with newly diagnosed AL amyloidosis as first line therapy. In addition, for the treatment of refractory or relapsed AL amyloidosis, where the availability of supporting literature is scant and extrapolated from the treatment of multiple myeloma, there is currently quality evidence to recommend the use of ixazomib, an oral reversible proteasome inhibitor, only available in Argentina since 2020. Finally, some research lines exploring the efficacy of other monoclonal antibodies and therapeutic experiments based on the use of CAR-T cells are mentioned. (AU)

Humans , B-Cell Maturation Antigen/therapeutic use , Immunoglobulin Light-chain Amyloidosis/drug therapy , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Recurrence , Practice Guidelines as Topic , Hematopoietic Stem Cell Transplantation
Rev. biol. trop ; 71(1): e54918, dic. 2023. graf
Article in English | LILACS, SaludCR | ID: biblio-1550731


Abstract Introduction: The therapeutic benefits of the brown algae fucoidan in the treatment of breast cancer have attracted considerable interest in recent years. However, research using spheroids which provide relevant results in trials for antitumor and immunomodulatory products because they adequately simulate the tumor microenvironment, is limited. Objective: To evaluate the antitumor and immunomodulatory activity of Lessonia trabeculata fucoidan (LtF), native to the Peruvian Sea, on two types of multicellular tumor spheroids. Methods: The study was conducted from January to December 2021. Two types of spheroides were elaborated: from 4T1 tumor cells (MTS), and from 4T1 tumor cells+mouse splenocytes (MTSs). The antitumor activity of LtF was evaluated in MTS by quantifying cell viability with MTT. Immunomodulatory activity was determined in MTSs using the IC50 for two types of treatment: simple, fucoidan alone (LtF) and combined, fucoidan+doxorubicin (LtF+Dox). Pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (IL-10, TGF-β) cytokine production was quantified by sandwich ELISA 72 h after treatment. Dox was used as positive control in all assays. Results: LtF exerted antitumor activity as evidenced by increased necrotic zone and cell debris formation compared to the untreated control. Antitumor activity was concentration dependent between 100 and 6 000 μg/ml. In MTSs, simple treatment increased IL-6 and decreased IL-10 and TGF-β production. The combined treatment significantly reduced TGF-β production. In both treatments and Dox, there was an increase in IL-6 compared to the untreated control. The highest production of IL-10 and TGF-β was observed in the untreated control, compatible with a highly immunosuppressive tumor microenvironment. Conclusions: LtF is a good candidate for the treatment of breast cancer and can immunomodulate the tumor microenvironment alone or in combination with Dox.

Resumen Introduccción: Los beneficios terapéuticos del fucoidan de algas pardas en el tratamiento del cáncer de mama han despertado gran interés en los últimos años. Sin embargo, las investigaciones con esferoides son limitadas, éstos proporcionan resultados relevantes en ensayos de productos antitumorales e inmunomoduladores porque simulan adecuadamente el microambiente tumoral. Objetivo: Evaluar la actividad antitumoral e inmunomoduladora del fucoidan de Lessonia trabeculata (LtF), nativa del Mar Peruano, en dos tipos de esferoides tumorales multicelulares. Métodos: El estudio se realizó de enero a diciembre de 2021. Se elaboraron dos tipos de esferoides: con células tumorales 4T1 (MTS) y con células tumorales 4T1+esplenocitos de ratón (MTSs). La actividad antitumoral de LtF se evaluó en MTS cuantificando la viabilidad celular con MTT. La inmunomodulación se determinó en MTSs utilizando la IC50 para dos tipos de tratamiento: simple, fucoidan solo (LtF) y combinado, fucoidan+doxorubicina (LtF+Dox). La producción de citoquinas proinflamatorias (TNF-α, IL-6) y antiinflamatorias (IL-10, TGF-β) se cuantificó mediante ELISA sándwich 72 h post-tratamiento. En todos los ensayos se utilizó Dox como control positivo. Resultados: En los MTS, el LtF ejerció actividad antitumoral evidenciada por aumento de la zona necrótica y formación de restos celulares respecto al control no tratado. La actividad antitumoral fue concentración-dependiente entre 100 y 6 000 μg/ml. En los MTSs, con el tratamiento simple se incrementó IL-6 y disminuyeron IL-10 y TGF-β. El tratamiento combinado redujo significativamente la producción de TGF-β. Los dos tratamientos y Dox incrementaron IL-6 respecto al control no tratado. La mayor producción de IL-10 y TGF-β se observó en los no tratados, compatible con un microambiente tumoral altamente inmunosupresor. Conclusiones: El LtF es un buen candidato para tratar el cáncer de mama y puede inmunomodular el microambiente tumoral solo o en combinación con Dox.

Animals , Spheroids, Cellular , Phaeophyceae , Antineoplastic Agents/therapeutic use , Peru
Respirar (Ciudad Autón. B. Aires) ; 15(3): [217-221], sept. 2023.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1510813


La toxicidad pulmonar por antineoplásicos es muy variable dependiente del grupo far-macológico; la bleomicina es uno de los medicamentos en los que se ha reportado este evento. Este citostático puede lesionar el endotelio pulmonar y el epitelio alveolar para llevar a un proceso inflamatorio y fibrótico del intersticio con repercusiones potencial-mente fatales.A continuación, se presenta un caso de enfermedad intersticial tipo neumonía organi-zada asociada a bleomicina en un paciente de 68 años con diagnóstico linfoma Hodg-kin clásico de tipo esclerosis nodular, con estudio imagenológico normal previo al tratamiento

Antineoplastic pulmonary toxicity is highly variable depending on the pharmacological group; bleomycin is one of the drugs in which this event has been reported. This cyto-static can injure the pulmonary endothelium and the alveolar epithelium to lead to an in-flammatory and fibrotic process of the interstitium with potentially fatal repercussions. The following is a case of interstitial disease type organizing pneumonia associated with bleomycin in a 68-year-old patient diagnosed with classical Hodgkin lymphoma of nodular sclerosis type, with imaging study prior to normal treatment

Humans , Male , Aged , Pulmonary Fibrosis , Bleomycin/toxicity , Hodgkin Disease/drug therapy , Tomography, X-Ray Computed , Antineoplastic Agents/therapeutic use
Rev. Ciênc. Plur ; 9(1): 27811, 27 abr. 2023. tab
Article in Portuguese | LILACS, BBO | ID: biblio-1428113


ntrodução:O câncer infantojuvenil corresponde a um grupo de várias doenças que têm em comum a proliferação descontrolada de células anormais e que pode ocorrer em qualquer local do organismo. Objetivo:Identificar os tipos de neoplasias mais frequentes na infância e adolescência e analisar o perfil clínico-epidemiológicodos pacientes. Metodologia:Estudo de transversal exploratório, de natureza aplicada com análise documental, realizado no Centro de Oncohematologia Pediátrica do Hospital Universitário Oswaldo Cruz, Recife, Pernambuco.Foram incluídos crianças e adolescentes diagnosticados com neoplasia e tratados por terapia antineoplásica.Os critérios de exclusão foram crianças e adolescentes normorreativas e/ou com doenças sistêmicas; prontuários ilegíveis ou com falta de informações clínicas.Resultados:Identificou-se que 54,21% dos pacientes eram dosexo feminino, seguido por 44,86% do sexo masculino.A faixa etária prevalente no estudo foi o de crianças de 5 a 14 anos (54,21%), ainda sobre o perfil dos pacientes, identificou-se que população autodeclarada como negra foi a mais prevalente representando 44,86% do total, seguido dos brancos com 43,93%. O diagnóstico que prevaleceu foi o de Leucemia Linfoide Aguda(23,36%), seguido pela Retinoblastoma (7,48%) e pela Rabdomiossarcoma embrionário (6,54%), e consequentemente o local da neoplasia primária que prevaleceu foi a Medula óssea (27,10%) seguido do olho (10,28%), deste total nota-se que o tratamento antineoplásico mais utilizado foi a quimioterapia (40,19%) seguido da quimioterapia associada à radioterapia(12,15%) e pela quimioterapia associada a cirurgia (10,28%). Conclusões:A leucemia linfoide aguda foi a neoplasia mais frequente na infância e adolescência, com prevalência na idade entre 5 e 14 anos, no sexo feminino e na etnia negra. A terapia antineoplásica mais utilizada foi a quimioterapia, seguida da associação entre quimioterapia e radioterapia (AU).

Introduction:Childhood cancer correspondsto a group of several diseases that have in common the uncontrolled proliferation of abnormal cells and that can occur anywhere in the body. Objective:Identify the most frequent types of neoplasms in childhood and adolescence and analyze the clinical-epidemiological profile of patients. Methodology:Exploratory cross-sectional study, applied in nature with document analysis, carried out at the Pediatric Oncohematology Center of Oswaldo Cruz University, Recife, Pernambuco. Children and adolescents diagnosed with neoplasia and treated with antineoplastic therapy were included. Exclusion criteria were normoreactive children and adolescents and/or with systemic diseases; illegible medical records or lacking clinical information. Results:It was identified that54.21% of the patients were female, followed by 44.86% male. The prevalent age group in the study was children from 5 to 14 years old (54.21%), still regarding the patients'profile , it was identified that the population self-declared as black was the most prevalent, representing 44.86% of the total, followed by of whites with 43.93%. The diagnosis that prevailed was Acute Lymphoid Leukemia (23.36%), followed by Retinoblastoma (7.48%) and Embryonic Rhabdomyosarcoma (6.54%), and consequently,the site of the primary neoplasm that prevailed was Bone marrow (27.10%) followed by the eye (10.28%), of this total it is noted that the most used anticancer treatment was chemotherapy (40.19%) followed by chemotherapy associated with radiotherapy (12.15% ) and chemotherapy associated with surgery (10.28%). Conclusions:Acute lymphoblastic leukemia was the most frequent neoplasm in childhood and adolescence, with a prevalence between 5 and 14 years of age, in females,and black ethnicity. The most used antineoplastic therapy was chemotherapy, followed by the association between chemotherapy and radiotherapy (AU).

ntroducción: El cáncer infantil corresponde a un grupo de varias enfermedades que tienen en común la proliferación descontrolada de células anormales y que pueden presentarse en cualquier parte del cuerpo. Objetivo: Identificar los tipos de neoplasias más frecuentes en la infancia y la adolescencia y analizar el perfil clínico-epidemiológico de los pacientes. Metodología: Estudio transversal exploratorio, aplicado en la naturaleza con análisis de documentos, realizado en el Centro de Oncohematología Pediátrica del Hospital Universitario Oswaldo Cruz, Recife, Pernambuco. Se incluyeron niños y adolescentes con diagnóstico de neoplasia y tratados con terapia antineoplásica. Los criterios de exclusión fueron niños y adolescentes normorreactivos y/o con enfermedades sistémicas; registros médicos ilegibles o carentes de información clínica. Resultados: Se identificó que el 54,21% de los pacientes eran del sexo femenino, seguido del 44,86% del masculino. El grupo etario prevalente en el estudio fueron los niños de 5 a 14 años (54,21%), en cuanto al perfil de los pacientes, se identificó que la población autodeclarada afrodescendiente fue la más prevalente, representando el 44,86% del total, seguido de los blancos con un 43,93%. El diagnóstico que predominó fue Leucemia Linfoide Aguda (23,36%), seguido de Retinoblastoma (7,48%) yRabdomiosarcoma Embrionario (6,54%), y en consecuencia el local de la neoplasia primaria que predominó fue Médula Ósea (27,10%) seguido de ocular (10,28%), de este total se destaca que el tratamiento anticancerígeno más utilizado fue la quimioterapia (40,19%) seguida de la quimioterapia asociada a radioterapia (12,15%) y la quimioterapia asociada a cirugía (10,28%). Conclusiones: La leucemia linfoblástica aguda fue la neoplasia más frecuente en la infancia y la adolescencia, con prevalencia entre los 5 y los 14 años, en el sexo femenino y en la etnia negra. La terapia antineoplásica más utilizada fue la quimioterapia, seguida de la asociación entre quimioterapia y radioterapia (AU).

Humans , Male , Female , Child , Adolescent , Health Profile , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Neoplasms/epidemiology , Antineoplastic Agents/therapeutic use , Medical Records , Cross-Sectional Studies/methods , Document Analysis , Hospitals, Pediatric
Rev. baiana enferm ; 37: e51209, 2023. tab, graf
Article in Portuguese | LILACS, BDENF | ID: biblio-1529647


Objetivos: identificar as percepções sobre o bem-estar, apoio social, intensidade dos sintomas e o seu impacto nas atividades diárias de pacientes com cânceres cerebrais e correlacionar os achados com os níveis de adesão aos quimioterápicos antineoplásicos orais. Método: estudo correlacional e transversal, realizado num ambulatório hospitalar universitário de São Paulo, Brasil, entre 2019 e 2020. Utilizou-se instrumento para caracterização da amostra e escalas específicas. Resultados: 26 participantes, mediana de 36,5 anos, 61,5% sexo masculino, 53,9% diagnosticados com glioblastoma; 73,1% apresentaram adesão, rede de apoio social e índice alto de bem-estar. O escore médio de intensidade dos sintomas foi de baixo para médio, com pior pontuação para preocupação no pior estado. A maior adesão relacionou-se ao apoio afetivo, apoio informação, interação social e apoio emocional. Conclusão: a maioria declarou níveis positivos de bem-estar, suporte social e poucos sintomas. A percepção de apoio social e bem-estar influenciaram positivamente na adesão medicamentosa.

Objetivos: identificar las percepciones sobre el bienestar, apoyo social, intensidad de los síntomas y su impacto en las actividades diarias de pacientes con cánceres cerebrales y correlacionar los resultados con los niveles de adhesión a los quimioterápicos antineoplásicos orales. Método: estudio correlacional y transversal, realizado en un ambulatorio hospitalario universitario de São Paulo, Brasil, entre 2019 y 2020. Se utilizó un instrumento para la caracterización de la muestra y escalas específicas. Resultados: 26 participantes, mediana de 36,5 años, 61,5% sexo masculino, 53,9% diagnosticados con glioblastoma; 73,1% presentaron adhesión, red de apoyo social y índice alto de bienestar. El puntaje promedio de intensidad de los síntomas fue de bajo a medio, con peor puntuación para preocupación en el peor estado. La mayor adhesión se relacionó al apoyo afectivo, apoyo información, interacción social y apoyo emocional. Conclusión: la mayoría declaró niveles positivos de bienestar, apoyo social y pocos síntomas. La percepción de apoyo social y bienestar influyó positivamente en la adhesión medicamentosa.

Objectives: to identify perceptions about well-being, social support, intensity of symptoms and their impact on the daily activities of patients with brain cancers and correlate the findings with levels of adherence to oral antineoplastic chemotherapy. Method: correlational and cross-sectional study, conducted in a university hospital outpatient clinic in São Paulo, Brazil, between 2019 and 2020. An instrument was used to characterize the sample, in addition to specific scales. Results: 26 participants, median 36.5 years, 61.5% male, 53.9% diagnosed with glioblastoma; 73.1% showed adherence, social support network and high well-being index. The mean symptom intensity score was low to medium, with a worse score for worry in the worst state. Greater adherence was related to affective support, information support, social interaction and emotional support. Conclusion: most reported positive levels of well-being, social support and few symptoms. The perception of social support and well-being positively influenced drug adherence.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Quality of Life , Social Support , Correlation of Data , Antineoplastic Agents/therapeutic use , Cross-Sectional Studies , Glioblastoma/psychology
Frontiers of Medicine ; (4): 685-698, 2023.
Article in English | WPRIM | ID: wpr-1010800


Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Humans , Antineoplastic Agents/therapeutic use , Apoptosis , beta Catenin/metabolism , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Coenzyme A Ligases/metabolism , Leukemia, Myeloid, Acute/metabolism , Lipoylation , Prognosis , Wnt Signaling Pathway
Chinese Journal of Surgery ; (12): 1035-1045, 2023.
Article in Chinese | WPRIM | ID: wpr-1007819


Recurrence of hepatocellular carcinoma (HCC) after surgery is a major factor affecting the efficacy of the treatment of patients. Neoadjuvant treatment is an effective therapeutic method to reduce postoperative recurrence and prolong patient survival. However,there is no generally accepted neoadjuvant treatment regimen that has been proven to be effective so far. Recently,with the progress in systemic antitumor therapies,represented by targeted molecular agents and immune checkpoint inhibitors,and the improvement in local regional therapies,these treatment approaches have shown promising efficacy and safety in the field of neoadjuvant treatment for HCC. Under the organizational leadership of Committee of Digestive Surgery of Chinese Research Hospital Association and Committee of Liver Cancer of Chinese Anti-Cancer Association,Alliance of Chinese Expert Consensus on Neoadjuvant Therapy for Hepatocellular Carcinoma has discussed and revised several times and finally formulated the Chinese expert consensus on neoadjuvant therapy for hepatocellular carcinoma (2023 edition). This consensus aimed to review the Chinese characteristics of the diagnosis and treatment of HCC,to provide specific guidance and suggestions for preoperative treatment strategies for HCC,and further promote the management of the clinical pathway for neoadjuvant treatment of HCC.

Humans , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/surgery , China , Consensus , Liver Neoplasms/pathology , Neoadjuvant Therapy
Journal of Experimental Hematology ; (6): 1394-1402, 2023.
Article in Chinese | WPRIM | ID: wpr-1009994


OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Humans , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Apoptosis Regulatory Proteins/immunology , Autophagy/immunology , bcl-2-Associated X Protein/immunology , Bortezomib/therapeutic use , Burkitt Lymphoma/immunology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Therapy, Combination , Proto-Oncogene Proteins c-akt , Proto-Oncogene Proteins c-bcl-2 , Receptors, CXCR/immunology , RNA, Messenger , TOR Serine-Threonine Kinases , Xanthones/therapeutic use
Journal of Experimental Hematology ; (6): 1014-1018, 2023.
Article in Chinese | WPRIM | ID: wpr-1009957


OBJECTIVE@#To analyze the efficacy and safety of flumatinib in the treatment of patients with chronic myeloid leukemia (CML).@*METHODS@#The clinical data of 56 CML patients treated with flumatinib from January 2020 to December 2021 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. Patients were divided into three groups: 35 new diagnosed CML patients treated with flumatinib (group A), 10 patients with imatinib/dasatinib intolerance (group B) and 11 patients with imatinib/dasatinib resistance (group C) switched to flumatinib treatment, respectively. The molecular response and adverse effects of flumatinib treatment were evaluated.@*RESULTS@#In group A, the early molecular response (EMR) at 3 months was 40.0%, and the major molecular response (MMR) at 6 and 12 months was 43.7% and 46.2%, respectively. In group B, the EMR was 50.0% at 3 months, and the MMR was 70.0% and 66.2% at 6 and 12 months, respectively. Among evaluable patients, 6 cases in group B achieved molecular response of 4.5 (MR4.5) at 12 months after switching to flumatinib treatment. In group C, 3 cases who switched from imatinib resistance to flumatinib achieved MR4.5 at 12 months, but 2 cases who switched from dasatinib resistance to flumatinib failed. Subgroup analysis showed significant differences in EUTOS long-term survival (ELTS) scores for patients in the medium-risk/high-risk group compared with those in the low-risk group for 3-month EMR (18.8% vs 57.9%), 6-month MMR (15.4% vs 63.2%) and 12-month MR4.5 (15.4% vs 69.2%) (P =0.036, P =0.012,P =0.015). The most common adverse effect in group A was thrombocytopenia, accounting for 54.5%, and 22.8% (8/35) patients discontinued the drug due to haematological adverse effects. Compared with patients who did not discontinue the drug or whose recovery time from discontinuation due to haematological toxicity was <1 month, patients whose recovery time from discontinuation was ≥1 month had a significantly worse 3-month EMR, 6-month MMR and 12-month MR4.5 (P =0.028, P =0.021, P =0.002).@*CONCLUSIONS@#Flumatinib has better molecular response and tolerance in patients with primary, imatinib/dasatinib-intolerant or resistant CML. Medium-risk/high-risk in ELTS score and time to recovery from discontinuation due to haematological toxicity ≥1 month are important factors influencing achievement of better molecular response in flumatinib treatment.

Humans , Imatinib Mesylate/therapeutic use , Dasatinib/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Benzamides/therapeutic use , Chronic Disease , Treatment Outcome , Antineoplastic Agents/therapeutic use
Chinese Journal of Hematology ; (12): 106-111, 2023.
Article in Chinese | WPRIM | ID: wpr-969684


Objective: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving initial imatinib therapy. Methods: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response (MMR) and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve (AUROC) was used to estimate accuracy of the predictive system. Results: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort (n=909) and validation cohort (n=455) . In the training cohort, the male gender, European Treatment and Outcome Study for CML (EUTOS) Long-Term Survival (ELTS) intermediate-risk, ELTS high-risk, high WBC (≥130×10(9)/L or 120×10(9)/L, MMR or MR4) and low HGB (<110 g/L) at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB (<110 g/L) were given 1 point; ELTS high-risk and high WBC (≥130×10(9)/L) , 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB (<110 g/L) were given 2 points; high WBC (≥120×10(9)/L) , 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort (all P values <0.001) . In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. Conclusions: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.

Adult , Humans , Male , Imatinib Mesylate/therapeutic use , Antineoplastic Agents/therapeutic use , Treatment Outcome , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Chronic Disease
Journal of Central South University(Medical Sciences) ; (12): 1128-1135, 2023.
Article in English | WPRIM | ID: wpr-1010336


OBJECTIVES@#Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms.@*METHODS@#This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting.@*RESULTS@#Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax).@*CONCLUSIONS@#The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.

Humans , Nasopharyngeal Carcinoma , Paclitaxel/therapeutic use , Nasopharyngeal Neoplasms/metabolism , Antineoplastic Agents/therapeutic use , Apoptosis , Cell Proliferation , Cell Line, Tumor
Chinese Journal of Lung Cancer ; (12): 245-256, 2023.
Article in Chinese | WPRIM | ID: wpr-982154


BACKGROUND@#Epidermal growth factor receptor (EGFR) gene mutations are the most common driver mutations in non-small cell lung cancer (NSCLC). To prolong the survival of the patients, EGFR tyrosine kinase inhibitors (TKIs) resistance in NSCLC is a major challenge that needs to be addressed urgently, and this study focuses on investigating the mechanism of cigarette smoke (CS) induced Gefitinib resistance in NSCLC.@*METHODS@#PC-9 and A549 cells were cultured in vitro and treated with 1 µmol/L Gefitinib for 4 h and 10% cigarette smoke extract (CSE) for 48 h. Western blot was used to detect Sirtuin 3 (Sirt3) and superoxide dismutase 2 (SOD2) protein expressions; DCFH-DA probe was used to detect intracellular reactive oxygen species (ROS); CCK-8 kit was used to detect cell activity, and EdU was used to detect cell proliferation ability. Sirt3 overexpression plasmid (OV-Sirt3) was transfected in PC-9 and A549 cells and treated with 1 µmol/L Gefitinib for 4 h and 10% CSE for 48 h after N-acetylcysteine (NAC) action. The expressions of Sirt3 and SOD2 were detected by Western blot; the ROS level in the cells was detected by DCFH-DA probe, and the cell activity was detected by CCK-8.@*RESULTS@#CSE induced an increase in the 50% inhibitory concentration (IC50) of both PC-9 and A549 cells to Gefitinib (P<0.01) and enhanced the proliferation of PC-9 and A549 cells, suggesting that CS induced Gefitinib resistance in NSCLC. ROS was involved in CSE-induced Gefitinib resistance (P<0.05). CSE induced low expressions of Sirt3 and SOD2 (P<0.01), and Sirt3/SOD2 was associated with poor prognosis in lung cancer patients (P<0.05). OV-Sirt3 in PC-9 and A549 cells reversed CSE-induced Gefitinib resistance (P<0.05) and significantly reduced ROS production. NAC reversed CSE-induced Gefitinib resistance in PC-9 and A549 cells (P<0.05).@*CONCLUSIONS@#The ROS/Sirt3/SOD2 pathway is involved in CS-induced Gefitinib resistance in NSCLC.

Humans , Gefitinib/therapeutic use , Carcinoma, Non-Small-Cell Lung/metabolism , Sirtuin 3/therapeutic use , Lung Neoplasms/metabolism , Reactive Oxygen Species/therapeutic use , Antineoplastic Agents/therapeutic use , Cigarette Smoking , Sincalide/therapeutic use , ErbB Receptors/metabolism , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor
Chinese Journal of Internal Medicine ; (12): 785-801, 2023.
Article in Chinese | WPRIM | ID: wpr-981055


Transarterial interventional therapy is one of the most widely used treatment methods in patients with primary hepatocellular carcinoma. With the progress in interventional technology and the use of new drugs, transarterial interventional therapy has achieved favorable results in the treatment of primary hepatocellular carcinoma and has become the first choice non-surgical treatment for advanced liver cancer. However, at present, there are great differences in the drugs used in transarterial interventional treatment and the combined application of other drugs among centers, and there is no uniform consensus or guideline. Based on the latest research data and clinical practice experience, as well as the characteristics of Chinese patients, the Specialist Group of Interventional Drugs, Interventionalists Branch of the Chinese Medical Doctor Association was organized to formulate the Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma. The purpose of this consensus is to explore the efficacy and safety of drugs and drug combinations related to intra-arterial interventional therapy, the use of drugs in special populations, the management of adverse reactions, and adjuvant drugs to provide a reference for clinical practice.

Humans , Carcinoma, Hepatocellular/pathology , Consensus , East Asian People , Liver Neoplasms/pathology , Pharmaceutical Preparations , Infusions, Intra-Arterial/methods , Antineoplastic Agents/therapeutic use , Drug Therapy, Combination/methods
Journal of Zhejiang University. Science. B ; (12): 207-220, 2023.
Article in English | WPRIM | ID: wpr-971481


A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

Female , Male , Humans , Cisplatin/pharmacology , Disulfiram/pharmacology , Testicular Neoplasms/drug therapy , Fanconi Anemia/drug therapy , Alcoholism/drug therapy , Drug Resistance, Neoplasm , Cell Line, Tumor , Substance Withdrawal Syndrome/drug therapy , Apoptosis , Antineoplastic Agents/therapeutic use , Cell Proliferation
Journal of Central South University(Medical Sciences) ; (12): 268-274, 2023.
Article in English | WPRIM | ID: wpr-971394


Pancreatic cancer (PC) is a malignant tumor of the digestive tract with poor patient prognosis. The PC incidence is still increasing with a 5-year survival rate of only 10%. At present, surgical resection is the most effective method to treat PC, however, 80% of the patients missed the best time for surgery after they have been diagnosed as PC. Chemotherapy is one of the main treating methods but PC is insensitive to chemotherapy, prone to drug resistance, and is accompanied by many side effects which are related to a lack of specific target. Exosomes are nanoscale vesicles secreted by almost all cell types and can carry various bioactive substances which mediate cell communication and material transport. They are characterized by a low immunogenicity, low cytotoxicity, high penetration potential and homing capacity, and possess the potential of being used as advanced drug carriers. Therefore, it is a hot research topic to use drug-loaded exosomes for tumor therapy. They may alleviate chemotherapy resistance, reduce side effects, and enhance the curative effect. In recent years, exosome drug carriers have achieved considerable results in PC chemotherapy studies.

Humans , Exosomes/metabolism , Drug Carriers/metabolism , Pancreatic Neoplasms/diagnosis , Antineoplastic Agents/therapeutic use
Journal of Central South University(Medical Sciences) ; (12): 182-190, 2023.
Article in English | WPRIM | ID: wpr-971384


OBJECTIVES@#Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1.@*METHODS@#Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence.@*RESULTS@#The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment.@*CONCLUSIONS@#WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

Animals , Male , Rats , Antineoplastic Agents/therapeutic use , Colitis, Ulcerative/chemically induced , Colon/pathology , Disease Models, Animal , Interleukin-6/pharmacology , Propolis/therapeutic use , Rats, Sprague-Dawley , Sulfasalazine/therapeutic use , TRPV Cation Channels , Tumor Necrosis Factor-alpha/pharmacology
Chinese Journal of Lung Cancer ; (12): 52-58, 2023.
Article in Chinese | WPRIM | ID: wpr-971179


As one of the most common malignant tumors, lung cancer poses a serious threat to human life and health. The platinum-based drug cisplatin (DDP) is used as the first-line treatment for lung cancer. The poor prognosis of lung cancer is mostly due to developed resistance to cisplatin, which poses a serious treatment challenge. The mechanism of cisplatin resistance is complex and unclear. Numerous studies have shown that DNA methylation plays a crucial role in the emergence of lung cancer cisplatin resistance. DNA hypermethylation results in the deactivation of numerous drug resistance genes and tumor suppressor genes through a change in chromatin conformation. Finding new therapeutic targets and indicators to predict the therapeutic effect can be aided by elucidating the complex mechanism. In order to discover novel strategies to overcome cisplatin resistance in lung cancer, this paper discusses DNA methylation-mediated cisplatin resistance and offers an overview of current demethylation procedures.

Humans , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cisplatin/therapeutic use , DNA Methylation , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/pathology