RESUMO
Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.
Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la "Conferencia de consenso de procedimientos operativos estandarizados de ESMO". Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.
Assuntos
Carcinoma Epitelial do Ovário , Medicina Baseada em Evidências , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/diagnóstico , Gradação de Tumores , Estadiamento de Neoplasias , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/diagnóstico , Consenso , Terapia CombinadaRESUMO
A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors such as half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 displayed the highest antiproliferative activity against the three cancer cells and were therefore further investigated. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Moreover, the expressions of key genes were studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking shows that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.
Assuntos
Antineoplásicos , Naftoquinonas , Neoplasias , Naftoquinonas/farmacologia , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
OBJECTIVE: Current evidence has shown how laparoscopic surgery results in shorter hospital stay, faster recovery, and better aesthetic results. However, we do not have information on populations in Latin America and the impact that the social environment has on quality of life in patients with gynecological cancer undergoing minimally invasive surgery. To assess quality of life of patients undergoing minimally invasive surgery in a gynecologic oncology department over time and to establish the relationship with patient and treatment variables. METHODS: This cross-sectional study evaluated the quality of life of women undergoing minimally invasive surgery from August 2019 to July 2021. The FACT-G (Functional Assessment of Cancer Therapy-General) scale encompasses global quality of life and four domains of physical, social, emotional, and functional components. This scale was applied to measure quality of life in the preoperative, early operative, and late postoperative periods. Additionally, mixed models were used to compare quality of life based on demographic and clinical factors after minimally invasive surgery. RESULTS: A total of 158 patients were analyzed. Belonging to a higher socioeconomic stratum (3 vs 1) had a positive impact on the global quality of life in patients undergoing surgery with an increase of 7.6 points (p=0.011). Also, a lower Charlson Index had a positive impact of 0.393 points for the physical component of quality of life (p=0.031). For the social component of quality of life, having a partner and being part of a higher socioeconomic stratum (3 and 2 vs 1) resulted in an increase of 2.11 (p=0.005), 4.06 (p<0.05), and 2.55 (p=0.004) points, respectively. Belonging to a higher socioeconomic stratum (3 vs 1) resulted in an increase of 2.03 points (p=0.031) for the functional component of quality of life. Finally, the complexity of the procedure, or whether the procedure was ambulatory or not did not impact quality of life. CONCLUSIONS: Lower Charlson Index, having a partner, or having higher socioeconomic status are all associated with higher quality of life of patients undergoing minimally invasive surgery.
Assuntos
Neoplasias dos Genitais Femininos , Qualidade de Vida , Humanos , Feminino , Estudos Transversais , Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-OperatóriasRESUMO
Valeriana pilosa is usually employed in Peruvian folk medicine in the form of infusion to treat stomach pain, and has antispasmodic, relaxing, sleep-promoting, and sedative properties, as well as is an anti-inflammatory. In this study, Valeriana pilosa essential oil (VPEO) was obtained by hydrodistillation, analyzed by GC and GC/MS, and 47 compounds were identified. Major oil components were α-patchoulene (5.8%), α-humulene (6.1%), seychellene (7.6%), and patchoulol (20.8%). Furthermore, we assessed the in vitro antioxidant activities, molecular docking, and Ligand Efficiency studies on enzymes involved in cellular redox pathways such as CYP2C9, catalase, superoxide dismutase, and xanthine oxidase. Essential oil antioxidant activities were assessed by FRAP, ABTSâ¢+, and DPPH⢠radical scavenging activity. VPEO displays high antioxidant activity as compared to essential oils of Valeriana jatamansi and Valeriana officinalis oil roots. In addition, molecular docking and ADMET prediction was employed to compare the absorption, metabolism, and toxicity properties of Valeriana pilosa compounds. In the molecular docking studies, limonene, p-cimene, carvone, α-cubebene, cyclosativene, α-guaiene, allo-aromadendrene, valencene, and eremophyllene were the compounds with the best docking score on CYP2C9 and xanthine oxidase. Thus, volatile components of Valeriana pilosa could be associated with the detected antioxidant activity, acting as putative inhibitors of CYP2C9 and xanthine oxidase.
RESUMO
The high rates of morbidity and mortality due to fungal infections are associated with a limited antifungal arsenal and the high toxicity of drugs. Therefore, the identification of novel drug targets is challenging due to the several resemblances between fungal and human cells. Here, we report the in vitro antifungal evaluation of two acylphenols series, namely 2-acyl-1,4-benzo- and 2-acyl-1,4-naphthohydroquinones. The antifungal properties were assessed on diverse Candida and filamentous fungi strains through the halo of inhibition (HOI) and minimal inhibitory concentration (MIC). The antifungal activities of 2-acyl-1,4-benzohydroquinone derivatives were higher than those of the 2-acyl-1,4-naphthohydroquinone analogues. The evaluation indicates that 2-octanoylbenzohydroquinone 4 is the most active member of the 2-acylbenzohydroquinone series, with MIC values ranging from 2 to 16 µg/mL. In some fungal strains (i.e., Candida krusei and Rhizopus oryzae), such MIC values of compound 4 (2 and 4 µg/mL) were comparable to that obtained by amphotericin B (1 µg/mL). The compound 4 was evaluated for its antioxidant activity by means of FRAP, ABTS and DPPH assays, showing moderate activity as compared to standard antioxidants. Molecular docking studies of compound 4 and ADMET predictions make this compound a potential candidate for topical pharmacological use. The results obtained using the most active acylbenzohydroquinones are promising because some evaluated Candida strains are known to have decreased sensitivity to standard antifungal treatments.
Assuntos
Antifúngicos , Micoses , Anfotericina B/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Candida , Fungos , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Micoses/microbiologiaRESUMO
Resumen ANTECEDENTES: El cáncer de vulva es relativamente raro, representa menos del 1% de los tumores malignos de la mujer; su incidencia aumenta con la edad. La variedad más frecuente es el carcinoma escamoso (80 al 90%), seguido del melanoma. En este reporte se revisa un carcinoma de origen glandular, como el hidradenoma papilífero del tipo glándula mamaria (mammary-like) de la vulva. CASO CLÍNICO: Paciente de 50 años, con una lesión papular en la vulva de dos años de evolución, con crecimiento lento y progresivo, ocasional sensación de masa y dolor, con colposcopia negativa, sin antecedentes de patología mamaria y con una biopsia previa que reportó hidradenoma papilífero vulvar. Se trató con resección completa de la lesión, con anestesia regional, con bordes libres, no se identificó algún componente infiltrante. En la actualidad permanece sin evidencia de recaída ni requerimiento de tratamientos adicionales durante el seguimiento. CONCLUSIÓN: El hidradenoma papilífero es una lesión benigna, poco frecuente, relacionada con las glándulas anogenitales de tipo mammary-like, con buen pronóstico. El tratamiento recomendado es la escisión quirúrgica, que casi siempre es curativa.
Abstract BACKGROUND: Vulvar cancer is relatively rare, representing less than 1% of malignant tumors in women; its incidence increases with age. The most frequent variety is squamous cell carcinoma (80 to 90%), followed by melanoma. In this report we review a carcinoma of glandular origin, such as papilliferous hydradenoma of the vulva of the mammary gland (mammary-like) type. CLINICAL CASE: We present a 50-year-old patient with 2 years evolution of a papular lesion on the vulva with slow and progressive growth, intermitent sensation of mass and pain, with negative colposcopy, no history of breast pathology and with a previous biopsy that reported vulvar papilliferous hydradenoma. She was treated with complete resection of the lesion under regional anesthesia, with free margins, without identifying an infiltrating component and currently without evidence of relapse or requirement of additional treatments. CONCLUSION: Papilliferous hidradenoma is a rare benign lesion related to the mammary-like anogenital glands, with a good prognosis and its recommended treatment is surgical excision, which is generally curative.
RESUMO
Resumen El melanoma primario de mucosas representa el 1% de todos los cánceres. Su localización en cuello uterino es rara y existen menos de 100 casos reportados en la literatura hasta la fecha. Los datos son limitados en cuanto su estadificación y tratamiento y su pronóstico es malo con tasas de supervivencia del 10% a 5 años. Se presenta el caso clínico de una paciente de 82 años con sangrado vaginal, con evidencia de una lesión melanótica en cuello uterino, la biopsia de la lesión reportó compromiso por tumor maligno pobremente diferenciado, con inmuno perfil que confirma melanoma maligno. Los estudios de extensión no mostraron enfermedad metastásica a distancia, se presentó el caso en junta multidisciplinaria de ginecología oncológica por lo que se indicó tratamiento con radioterapia pélvica externa exclusiva con intención paliativa para control de síntomas, teniendo en cuenta: la edad, las comorbilidades y el estado funcional ECOG (Eastern Cooperative Oncology Group) 3; luego de 10 meses de seguimiento la paciente falleció.
Abstract Primary mucosal melanoma represents 1% of all cancers, the location in the cervix is rare, there are less than 100 cases reported in the literature to date, the data is limited in terms of staging and treatment, its prognosis is poor with survival rates of 10% at 5 years. We present a clinical case of a primary melanoma of the cervix in an 82-year-old patient with vaginal bleeding with evidence of a melanotic lesion in the cervix. The biopsy of the lesion reported poorly differentiated malignant tumor involvement, with an immuno-profile that favors melanoma. Extension studies were performed that did not show distant metastatic disease, the case was presented in a multidisciplinary oncological gynecology meeting, indicating treatment with exclusive external pelvic radiotherapy with palliative intention for symptom control taking into account patient comorbidities and ECOG functional status. (Eastern Cooperative Oncology Group) 3, after 10 months of follow-up the patient died.
Assuntos
Feminino , Idoso de 80 Anos ou mais , Terapêutica , Colo do Útero , MelanomaRESUMO
The reaction of 2-acyl-1,4-naphthoquinones with N,N-dimethylaniline and 2,5-dimethoxyaniline, promoted by catalytic amounts of CeCl3·7H2O under "open-flask" conditions, produced a variety of 2-acyl-3-aminophenyl-1,4-naphthoquinones structurally related to the cytotoxic 2-acetyl-3-phenyl-1,4-naphthoquinone, an inhibitor of the heat shock chaperone protein Hsp90. The members of the 2-acyl-3-aminophenyl-1,4-naphthoquinone series were isolated in good yields (63-98%). The cyclic voltammograms of the 2-acyl-3-aminophenyl-1,4-naphthoquinone exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasireversible oxidation peaks. The first and second half-wave potential values (E 1/2) of the members of the series are sensitive to the push-pull electronic effects of the substituents in the naphthoquinone scaffold. Furthermore, the in vitro antiproliferative properties of these new quinones were evaluated on two human cancer cells DU-145 (prostate) and MCF-7 (mammary) and a nontumorigenic HEK-293 (kidney) cell line, using the MTT colorimetric method. Two members, within the series, exhibited interesting cytotoxic activities on human prostate and mammary cancer cells.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Naftoquinonas/farmacologia , Antineoplásicos/síntese química , Antioxidantes/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Técnicas Eletroquímicas , Feminino , Células HEK293 , Humanos , Masculino , Naftoquinonas/química , Oxirredução , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Relação Estrutura-AtividadeRESUMO
A series of benzo[g]benzothiazolo[2,3-b]quinazoline-7,12-quinones were prepared from 2-acylnaphthohydroquinones and 2-aminobenzothiazoles and were evaluated for their in vitro antiproliferative activity. After screening using the MTT reduction assay, their IC50 values were calculated on a panel of cancer cells (T24, DU-145, MCF-7). Current standard anticancer drugs were included as control, and their calculated IC50 values were 7.8 and 23.5 µM for 5-fluorouracil and tamoxifen, respectively. Non-cancer cells (AG1523) were included to assess cancer cell sensitivity and drug selectivity. Four members of the series, with IC50 values from 0.11 to 2.98 µM, were chosen for further assays. The selected quinones were evaluated regarding their effects on cancer cell proliferation (clonogenic assay) and on Hsp90 and poly(ADPribose)polymerase (PARP) protein integrity. The most active compound (i.e., 15) substantially inhibited colony forming unit (CFU) formation at 0.25 µM. In the presence of ascorbate, it induced an oxidative cleavage of Hsp90 but had no effect on PARP protein integrity. In an in vivo animal model, it discreetly increased the mean survival time (m.s.t.) of tumor-bearing mice. In light of these results, compound 15 represents a potential lead-molecule to be further developed.
Assuntos
Antineoplásicos , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSP90 , Proteínas de Neoplasias , Neoplasias Experimentais , Quinazolinas , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Ascórbico , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Células MCF-7 , Camundongos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Quinazolinas/síntese química , Quinazolinas/química , Quinazolinas/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A broad range of 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones were synthesized and their voltammetric values, as well as in vitro cancer cell cytotoxicities, were assessed. The members of this series were prepared from acylbenzoquinones and phenylamines, in moderate to good yields (47-74%), through a procedure involving a sequence of two in situ regioselective oxidative amination reactions. The cyclic voltammograms of the aminoquinones exhibit two one-electron reduction waves to the corresponding radical-anion and dianion, and two quasi-reversible oxidation peaks. The first and second half-wave potential values (E1/2) of the members of the series were sensitive to the push-pull electronic effects of the substituents around the benzoquinone nucleus. The in vitro cytotoxic activities of the 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones against human cancer cells (bladder and prostate) and non-tumor human embryonic kidney cells were measured using the MTT colorimetric method. The substitution of both aniline groups, by either methoxy (electron donating effect) or fluorine (electron withdrawal effect), decreased the cytotoxicity in the aminoquinones. Among the members of the unsubstituted phenylamino series, two of the 18 compounds showed interesting anti-cancer activities. A preliminary assay, looking for changes in the expression of selected genes, was performed. In this context, the two compounds increased TNF gene expression, suggesting an association with an inflammatory-like response.
Assuntos
Benzoquinonas/farmacologia , Neoplasias/patologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzoquinonas/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Concentração Inibidora 50 , Conformação Molecular , Neoplasias/genéticaRESUMO
The composition of the essential oil obtained by hydrodistillation from Minthostachys mollis Griseb (Lamiaceae) aerial parts was determined by GC and GC/MS. Menthone (13.2%), pulegone (12.4%), cis-dihydrocarvone (9.8%) and carvacrol acetate (8.8%) were the main essential oil components. The cytotoxic activity of the essential oil was in vitro measured using the MTT colorimetric assay. IC50 values were calculated on healthy non-tumor cells (HEK-293) and three human cancer cell lines (T24, DU-145 and MCF-7). In such latter cells, the estimated values were around 0.2 mg/mL. In addition, the antioxidant activity was determined by interaction with the stable free radical 2,2"-diphenyl-1-picrylhydrazyl. The essential oil was almost devoid of antioxidant activity indicating that its anti-proliferative action relies on other unknown mechanism.
La composicioÌn del aceite esencial obtenido por hidrodestilacioÌn a partir de partes aeÌreas de Minthostachys mollis Griseb (Lamiaceae) se determinoÌ mediante GC y GC/MS. Mentona (13.2%), pulegona (12.4%), junto con cis-dihidrocarvona (9.8%) y acetato de carvacrol (8.8%) fueron los principales componentes del aceite esencial. La actividad citotoÌxica del aceite esencial se midioÌ in vitro utilizando el ensayo colorimeÌtrico MTT tanto en ceÌlulas sanas no tumorales (HEK-293) como en tres liÌneas celulares de caÌncer humano (T24, DU-145 y MCF-7). Los valores de IC50 calculados fueron de alrededor de 0.2 mg/mL. AdemaÌs, se determinoÌ la actividad antioxidante por su interaccioÌn con el radical libre 2,2"-difenil-1-picrilhidrazilo. El aceite esencial tiene baja actividad antioxidante, lo que indica que su accioÌn antiproliferativa depende de otro mecanismo desconocido.
Assuntos
Óleos Voláteis/farmacologia , Lamiaceae , Linhagem Celular Tumoral/efeitos dos fármacos , Antioxidantes/farmacologia , Peru , Picratos , Terpenos/análise , Bioensaio , Compostos de Bifenilo , Calorimetria , Óleos Voláteis/química , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres , Cromatografia Gasosa-Espectrometria de Massas , Antioxidantes/químicaRESUMO
Infection by Helicobacter pylori increases 10 times the risk of developing gastric cancer. Juglone, a natural occurring 1,4-naphthoquinone, prevents H. pylori growth by interfering with some of its critical metabolic pathways. Here, we report the design, synthesis, and in vitro evaluation of a series of juglone derivatives, namely, 2/3-phenylaminojuglones, as potential H. pylori growth inhibitors. Results show that 5 out of 12 phenylaminojuglones (at 1.5 µg/mL) were 1.5-2.2-fold more active than juglone. Interestingly, most of the phenylaminojuglones (10 out of 12) were 1.1-2.8 fold more active than metronidazole, a known H. pylori growth inhibitor. The most active compound, namely, 2-((3,4,5-trimethoxyphenyl)amino)-5-hydroxynaphthalene-1,4-dione 7, showed significant higher halo of growth inhibitions (HGI = 32.25 mm) to that of juglone and metronidazole (HGI = 14.50 and 11.67 mm). Structural activity relationships of the series suggest that the nature and location of the nitrogen substituents in the juglone scaffold, likely due in part to their redox potential, may influence the antibacterial activity of the series.
Assuntos
Antibacterianos/uso terapêutico , Produtos Biológicos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Naftoquinonas/uso terapêutico , Antibacterianos/farmacologia , Produtos Biológicos/farmacologia , Humanos , Naftoquinonas/farmacologia , OxirreduçãoRESUMO
The composition of the essential oil obtained by hydrodistillation from Dalea strobilacea Barneby (Fabaceae) aerial parts was examined by GC and GC/MS. beta-Phellandrene (44 percent) together with alpha-pinene (18 percent) were the main essential oil components. Antimicrobial activity of the essential oil was evaluated against eight bacterial strains. A moderate growth inhibition of Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis was shown by the essential oil.
La composición del aceite esencial de Dalea strobilacea Barneby (Fabaceae) obtenido por hidrodestilación de las partes aereas fue examinada por CG y CG/EM. beta-felandreno (44 por ciento) junto con alfa-pineno (18 por ciento) fueron los principales componentes del aceite esencial. La actividad antimicrobiana del aceite esencial fue evaluada contra ocho cepas bacterianas. El aceite esencial inhibió moderadamente el crecimiento de Klebsiella pneumoniae, Staphylococcus aureus y Enterococcus faecalis.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Bactérias , Fabaceae/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Destilação , Enterococcus faecalis , Cromatografia Gasosa-Espectrometria de Massas , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Staphylococcus aureusRESUMO
The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7, a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl2 (10-3 M), an inward rectifying K+ channels blocker, and blocked the vasodilation to KCl (10-2 M) in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10-8 M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+ channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.
RESUMO
A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 µM and also by their good selectivity indexes (≥2.24).
Assuntos
Aminoácidos , Antineoplásicos , Citotoxinas , Neoplasias/tratamento farmacológico , Quinolonas , Aminoácidos/síntese química , Aminoácidos/química , Aminoácidos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Quinolonas/síntese química , Quinolonas/química , Quinolonas/farmacologiaRESUMO
In the present study, we investigated sun protection factor and antioxidant properties of Parastrephia lepidophyla Cabr., Fabiana squamata Phil., Ephedra chilensis K.Presl., Lampaya medicinalis Phil., Baccharis tola Phil., and Azorella compacta Phil. The ethanol extracts were tested regarding their in vitro free radical scavenger ability and sun protection factor (SPF). Due to its antioxidant and photoprotective properties, B. tola is a promising candidate for use in cosmetic formulations. To evaluate the regenerative capacity of the B. tola extract, the planarian regeneration assay (Dugesia tigrina) was performed. Identification of phenolic compounds in B. tola, was performed by HPLC-ESI-MS/MS. Based on freeze-dried extracts of B. tola, a facial cream and a biphasic lotion with repairing tip action were formulated. These two formulations were evaluated by additional assays including organoleptic tests, measurement of pH, centrifugation and patch test to check a potential hypersensitivity (skin irritation) which can be induced by the products as well as a sensory survey. Stability studies, carried out over 12 months, prove that formulations were stable over time. It can be concluded that both products are innovative and shown solar protection, antioxidant and regenerative properties.
En el presente estudio, hemos investigado el factor de protección solar y propiedades antioxidantes de Parastrephia lepidophyla Cabr., Fabiana squamata Phil., Ephedra chilensis K.Presl., Lampaya medicinalis Phil., Baccharis tola Phil., y Azorella compacta Phil. Los extractos etanolicos fueron sometidos a ensayos como: evaluación in vitro de la actividad atrapadora de radicales libres y factor de protección solar (FPS). Debido a las propiedades antioxidantes y fotoprotectoras, B. tola es un candidato ideal para ser usado en formulaciones cosméticas. Se evaluó la capacidad regenerativa de B. tola en ensayos de planaria (Dugesia tigrina). Se identificó polifenoles por HPLC-ESI-MS/MS en B. tola. Se formularon una crema facial y una loción bifásica reparadora de puntas del cabello, en base a extractos liofilizados de Ñaca, a los cuales se le realizaron controles organolépticos, evaluación de pH, centrifugación, test de parche para evaluar la posible reacción de sensibilidad que pueden ocasionar los productos, comprobando que estos no producen irritación dérmica y posterior encuesta sensorial. Posteriormente, se realizaron estudios de estabilidad a lo largo de 12 meses, demostrando ser estable en el tiempo. Se puede concluir que ambos productos son innovadores y que muestran factor de protección solar, propiedades antioxidantes y regeneradoras.
Assuntos
Antioxidantes/química , Extratos Vegetais/química , Protetores Solares/química , Chile , Cromatografia Líquida de Alta PressãoRESUMO
The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days. Control group was treated with excipient. Previous tests selected the doses of juglone and Q7 plus ascorbate (1 and 100 mg/kg, respectively). Samples of ascitic fluid were collected to evaluate carbonyl proteins, GSH and activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Hypoxia inducible factor HIF-1α, GLUT1, proteins driving cell cycle (p53, p16 and cyclin A) and apoptosis (poly-ADP-polymerase PARP, Bax and Bcl-xL) were assessed by western blot. Tumor cells were categorized by the phase of cell cycle using flow cytometry and type of cell death using acridine orange/ethidium bromide. A glucose uptake assessment was performed by liquid scintillation using Ehrlich tumor cells cultured with (14)C-deoxyglucose. Treatments caused increased protein carbonylation and activity of antioxidant enzymes and decreased levels of GSH, HIF-1α, GLUT1 and glucose uptake in tumor cells. They also caused increased number of tumor cells in G1, p53 and p16 activation and decreased cyclin A, but only when combined with ascorbate. Apoptosis was induced mostly when treatments were done with ascorbate, causing PARP and Bax cleavage, and increased Bax/Bcl-xL ratio. Juglone and Q7 in combination with ascorbate caused inhibition of tumor progress in vivo by triggering apoptosis and cell cycle arrest associated with oxidative stress, suppression of HIF-1 and uncoupling of glycolytic metabolism.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Aminofenóis/administração & dosagem , Animais , Ácido Ascórbico/administração & dosagem , Carcinoma de Ehrlich/patologia , Progressão da Doença , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Naftoquinonas/administração & dosagemRESUMO
Dihydroxynaphthyl aryl ketones 1-5 have been evaluated for their abilities to inhibit microtubule assembly and the binding to tubulin. Compounds 3, 4 and 5 displayed competitive inhibition against colchicine binding, and docking analysis showed that they bind to the tubulin colchicine-binding pocket inducing sheets instead of microtubules. Remarkable differences in biological activity observed among the assayed compounds seem to be related to the structure and position of the aryl substituent bonded to the carbonyl group. Compounds 2, 3 and 4, which contain a heterocyclic ring, presented higher affinity for tubulin compared to the carbocyclic analogue 5. Compound 4 showed the best affinity of the series, with an IC50 value of 2.1 µM for microtubule polymerization inhibition and a tubulin dissociation constant of 1.0 ± 0.2 µM, as determined by thermophoresis. Compound 4 was more efficacious in disrupting microtubule assembly in vitro than compound 5 although it contains the trimethoxyphenyl ring present in colchicine. Hydrogen bonds with Asn101 of α-tubulin seem to be responsible for the higher affinity of compound 4 respects to the others.
Assuntos
Colchicina/metabolismo , Cetonas/metabolismo , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Animais , Sítios de Ligação , Ligação Competitiva , Galinhas , Colchicina/farmacologia , Ligação de Hidrogênio , Cetonas/química , Cetonas/farmacologia , Cinética , Microtúbulos/efeitos dos fármacos , Modelos Moleculares , Simulação de Dinâmica Molecular , Ligação Proteica , Relação Estrutura-Atividade , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologiaRESUMO
The aim of this study was to enhance the understanding of the antitumor mechanism of 1,4-naphthoquinones and ascorbate. Juglone, phenylaminonaphthoquinone-7, and 9 (Q7/Q9) were evaluated for effects on CT-DNA and DNA of cancer cells. Evaluations in MCF-7 cells are DNA damage, ROS levels, viability, and proliferation. Proteins from MCF-7 lysates were immunoblotted for verifying PARP integrity, γH2AX, and pAkt. Antitumor activity was measured in Ehrlich ascites carcinoma-bearing mice. The same markers of molecular toxicity were assessed in vivo. The naphthoquinones intercalate into CT-DNA and caused oxidative cleavage, which is increased in the presence of ascorbate. Treatments caused DNA damage and reduced viability and proliferation of MCF-7 cells. Effects were potentiated by ascorbate. No PARP cleavage was observed. Naphthoquinones, combined with ascorbate, caused phosphorylation of H2AX and inhibited pAkt. ROS were enhanced in MCF-7 cells, particularly by the juglone and Q7 plus ascorbate. Ehrlich carcinoma was inhibited by juglone, Q7, or Q9, but the potentiating effect of ascorbate was reproduced in vivo only in the cases of juglone and Q7, which caused up to 60% inhibition of tumor and the largest extension of survival. Juglone and Q7 plus ascorbate caused enhanced ROS and DNA damage and inhibited pAkt also in Ehrlich carcinoma cells.
Assuntos
Antineoplásicos/uso terapêutico , Ácido Ascórbico/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Dano ao DNA/efeitos dos fármacos , Naftoquinonas/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Histonas/metabolismo , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Naftoquinonas/química , Naftoquinonas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Different concentrations of essential oil obtained from Acantholippia deserticola (Phil.ex F. Phil.) Moldenke were assessed against Chilean agricultural pests like Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker, and Tetranychus urticae Koch. Thebioassays were carried out under laboratory conditions and both direct and residual applications were done through Potter precision spraytower test. The oil was obtained by steam distillation containing a rich fraction of alpha and beta-thujones (88.4 percent) and it shows marked toxic effects against pests. Indeed, a mortality of 82 percent and 89 percent was observed in both B. chilensis and T. urticae after 48 h whereas in A. floccosus over 97 percent of mortality was seen after 7 days. These results open the possibility to use essential oil from Acantholippia deserticola as natural pesticide.
Se evaluó el efecto a diferentes concentraciones de una solución de aceite esencial de Acantholippia deserticola sobre plagas agrícolas en Chile, tales como Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker y Tetranychus urticae Koch. Los bioensayos fueron realizados mediante una torre de Potter en condiciones de laboratorio y las aplicaciones fueron directas y residuales. El aceite se obtuvo por hidrodestilación, el cual contenía una gran cantidad de alfa and beta-tuyonas (88.4 por ciento), mostrando marcados efectos tóxicos para A. floccosus, con un 97 por ciento de mortalidad después de 7 d y, para B. chilensis, y T. urticae, con una mortalidad de 82 por ciento y 89 por ciento respectivamente, después de 48 h. Estos resultados abren la posibilidad de usar aceite esencial de Acantholippia deserticola como pesticida natural.