RESUMEN
Breast cancer stands as the most prevalent and heterogeneous malignancy affecting women globally, posing a substantial health concern. Enhanced comprehension of tumor pathology and the development of novel therapeutics are pivotal for advancing breast cancer treatment. Contemporary breast cancer investigation heavily leans on in vivo models and conventional cell culture techniques. Nonetheless, these approaches often encounter high failure rates in clinical trials due to species disparities and tissue structure variations. To address this, three-dimensional cultivation of organoids, resembling organ-like structures, has emerged as a promising alternative. Organoids represent innovative in vitro models that mirror in vivo tissue microenvironments. They retain the original tumor's diversity and facilitate the expansion of tumor samples from diverse origins, facilitating the representation of varying tumor stages. Optimized breast cancer organoid models, under precise culture conditions, offer benefits including convenient sample acquisition, abbreviated cultivation durations, and genetic stability. These attributes ensure a faithful replication of in vivo traits of breast cancer cells. As intricate cellular entities boasting spatial arrangements, breast cancer organoid models harbor substantial potential in precision medicine, organ transplantation, modeling intricate diseases, gene therapy, and drug innovation. This review delivers an overview of organoid culture techniques and outlines future prospects for organoid modeling.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Evaluación Preclínica de Medicamentos , Detección Precoz del Cáncer , Organoides , Microambiente TumoralRESUMEN
Physalis plants are commonly used traditional medicinal herbs, and most of their extracts containing withanolides show anticancer effects. Physapruin A (PHA), a withanolide isolated from P. peruviana, shows antiproliferative effects on breast cancer cells involving oxidative stress, apoptosis, and autophagy. However, the other oxidative stress-associated response, such as endoplasmic reticulum (ER) stress, and its participation in regulating apoptosis in PHA-treated breast cancer cells remain unclear. This study aims to explore the function of oxidative stress and ER stress in modulating the proliferation and apoptosis of breast cancer cells treated with PHA. PHA induced a more significant ER expansion and aggresome formation of breast cancer cells (MCF7 and MDA-MB-231). The mRNA and protein levels of ER stress-responsive genes (IRE1α and BIP) were upregulated by PHA in breast cancer cells. The co-treatment of PHA with the ER stress-inducer (thapsigargin, TG), i.e., TG/PHA, demonstrated synergistic antiproliferation, reactive oxygen species generation, subG1 accumulation, and apoptosis (annexin V and caspases 3/8 activation) as examined by ATP assay, flow cytometry, and western blotting. These ER stress responses, their associated antiproliferation, and apoptosis changes were partly alleviated by the N-acetylcysteine, an oxidative stress inhibitor. Taken together, PHA exhibits ER stress-inducing function to promote antiproliferation and apoptosis of breast cancer cells involving oxidative stress.
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Neoplasias de la Mama , Endorribonucleasas , Humanos , Femenino , Endorribonucleasas/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Apoptosis , Estrés Oxidativo , Estrés del Retículo Endoplásmico , Línea Celular TumoralRESUMEN
Triple-negative breast cancer (TNBC) is characterized by the loss of expression of several biomarkers, which limits treatment strategies for the disease. In recent years, immunotherapy has shown promising results in the treatment of various tumors. Emerging evidence demonstrated that TNBC is an immune-activated cancer, suggesting that immunotherapy could be a feasible treatment option for TNBC. Cytokine-induced killer (CIK) cell therapy is considered as a potential treatment for cancer treatment. However, it is still not approved as a standard treatment in the clinical setting. Our previous study demonstrated that focal adhesion kinase (FAK) plays important role in regulating the sensitivity of TNBC cells to CIK cells. In this study, we further verify the role of FAK in regulating the immune response in vivo. Our in vitro study indicated that knockdown of FAK in TNBC cells or treat with the FAK inhibitor followed by co-culture with CIK cells induced more cell death than CIK cells treatment only. RNA-seq analysis indicated that suppression of FAK could affect several immune-related gene expressions in TNBC cells that affects the immune response in the tumor microenvironment of TNBC cells. The combination of FAK inhibitor and CIK cells significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone in vivo. Our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment and indicate that the combination of CIK cell therapy with FAK inhibitors may be an alternative therapeutic strategy for patients with TNBC.
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Antineoplásicos , Células Asesinas Inducidas por Citocinas , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/metabolismo , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Antineoplásicos/uso terapéutico , Inmunoterapia/métodos , Inmunoterapia Adoptiva , Microambiente TumoralRESUMEN
Nepenthes plants are regarded as a kind of Traditional Chinese Medicine for several diseases but its anticancer activity remain unclear. The subject of this study is to evaluate the antiproliferation effects on oral cancer cells by Nepenthes plants using ethyl acetate extract of Nepenthes adrianii x clipeata (EANA). Cell viability was detected using MTS assay. Its detailed mechanisms including cell cycle, apoptosis, oxidative stress, and DNA damage were explored by flow cytometry or western blotting. For 24 hours EANA treatment, five kinds of oral cancer cells (CAL 27, Ca9-22, OECM-1, HSC-3, and SCC9) show IC50 values of cell viability ranging from 8 to 17 µg/mL but the viability of normal oral cells (HGF-1) remains over 80%. Subsequently, CAL 27 and Ca9-22 cells with high sensitivity to EANA were chosen to investigate the detailed mechanism. EANA displays the time course and concentration effects for inducing apoptosis based on flow cytometry (subG1 and annexin V analyses) and western blotting [cleaved poly (ADP-ribose) polymerase (c-PARP)]. Oxidative stress and DNA damage were induced by EANA treatments in oral cancer cells through reactive oxygen species (ROS), mitochondrial membrane potential disruption, mitochondrial superoxide, and γH2AX. All these changes of EANA treatments in oral cancer cells were reverted by the ROS scavenger N-acetylcysteine pretreatment. Therefore, EANA induces preferential killing, apoptosis, and DNA damage against oral cancer cells through oxidative stress.
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Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Estrés Oxidativo , Tracheophyta , Acetatos , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias de la Boca/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Nineteen compounds, including seven triterpenoids (1-7), five steroids (8-12), four cyclohexenone derivatives (13-16), two benzenoid glycosides (17 and 18) and one lignan (19), were isolated and separated from the leaves of Pandanus utilis through bioactivity-guided fractionation. Among them, one new lanosterol- type triterpenoid was found and named as (24R)-24-methyl-5a-4-demethyllanosta-9(11),25-dien-3ß-ol (1). The structures of the isolates were determined by mass and spectroscopic analyses, and the compounds were subjected to anti-inflammatory, anti-oxidative and cytotoxic assays.
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Pandanaceae/química , Hojas de la Planta/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular Tumoral , Glicósidos/química , Humanos , Lignanos/química , Modelos Moleculares , Estructura Molecular , Esteroides/química , Triterpenos/químicaRESUMEN
Development of an efficient treatment for triple-negative breast cancer is an urgent issues. Compounds from plant extracts are a potential source of novel cancer treatment. Isolinderalactone, a kind of sesquiterpenoids compound, was purified from the root of Lindera strychnifolia and Neolitsea daibuensis and shows anti-inflammatory and anticancer capacity. In the present study, isolinderalactone induced apoptosis in MDA-MB-231 cells which is a kind of triple-negative breast cancer cell line through induction of an intrinsic mitochondria-mediated and caspase-independent cell death. Treatment of isolinderalactone increased the protein level of the suppressor of cytokine signaling 3 (SCOS3), decreased phosphorylation of the signal transducer and activator of transcription 3 (STAT3), and suppressed expression of the down-stream genes of the X-linked inhibitor of apoptosis protein in MDA-MB-231 cells. Our results further showed that the level of SOCS3 expression was induced by isolinderalactone due to inhibiting the microRNA hsa-miR-30c-5p (miR-30c) expression. In addition, intraperitoneal injection of isolinderalactone induced apoptosis in a xenograft breast tumor while it did not significantly affect the histology of liver, kidney and lung of the treated mice. In conclusion, isolinderalactone induces apoptosis in MDA-MB231 cells and suppresses STAT3 signaling pathway through regulation of SOCS3 and miR-30c. It may become a novel treatment for triple-negative breast cancer in the future.
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MicroARNs/genética , Factor de Transcripción STAT3/biosíntesis , Sesquiterpenos/administración & dosificación , Proteínas Supresoras de la Señalización de Citocinas/biosíntesis , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Proteína Inhibidora de la Apoptosis Ligada a X/biosíntesis , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Lindera/química , Ratones , MicroARNs/biosíntesis , Factor de Transcripción STAT3/genética , Transducción de Señal/efectos de los fármacos , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Utilizing the pER8:GUS transgenic plant bioassay system to monitor estrogenic activity-guided fractionation, one new constituent, erycaffrain A, together with I known compounds were isolated from the ethanolic extract of Erythrina caffra. The structures of the isolated compounds were identified in combination with spectroscopic analyses. This is the first study reporting the estrogenic activity of E. caffra. The new compound exhibited as a SREM, but.also showed both estrogenic and anti-estrogenic activities in the MCF-7 cancer cell model. Several known phytoestrogens in this plant also revealed possible new functions for E. caffra stem.
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Erythrina/química , Antagonistas de Estrógenos/química , Estrógenos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antagonistas de Estrógenos/farmacología , Estrógenos/farmacología , Genes Reporteros , Humanos , Células MCF-7 , Estructura Molecular , Plantas Modificadas GenéticamenteRESUMEN
Acute radiation dermatitis is a frequent adverse effect in patients with breast cancer undergoing radiotherapy, but there are only a small number of studies providing evidence-based interventions for this clinical condition. Adlay is a cereal crop that has been previously shown to have anti-inflammatory and antioxidant properties. In this study, we seek to evaluate the effectiveness of oral prophylactic treatment with adlay bran extract in reducing the risk of severe acute radiation dermatitis. A total of 110 patients with breast cancer undergoing radiotherapy were analyzed. Using a prospective, randomized, double-blind design, 73 patients received oral treatment with adlay bran extract and 37 patients received olive oil (placebo). Treatment was started at the beginning of radiation therapy and continued until the termination of radiation treatment. Our results showed that the occurrence of severe acute radiation dermatitis (RTOG grade 2 or higher) was significantly lower in patients treated with oral adlay bran extract compared to placebo (45.2% versus 75.7%, adjusted odds ratio 0.24). No serious adverse effects from adlay bran treatment were noted. In conclusion, prophylactic oral treatment with adlay bran extract reduces the risk of severe acute radiation dermatitis and may have potential use in patients with breast cancer undergoing radiotherapy.
RESUMEN
Pandanus amaryllifolius Roxb. (Pandanaceae) is used as a flavor and in folk medicine in Southeast Asia. The ethanolic crude extract of the aerial parts of P. amaryllifolius exhibited antioxidant, antibiofilm, and anti-inflammatory activities in previous studies. In the current investigation, the purification of the ethanolic extract yielded nine new compounds, including N-acetylnorpandamarilactonines A (1) and B (2); pandalizines A (3) and B (4); pandanmenyamine (5); pandamarilactones 2 (6) and 3 (7), and 5(E)-pandamarilactonine-32 (8); and pandalactonine (9). The isolated alkaloids, with either a γ-alkylidene-α,ß-unsaturated-γ-lactone or γ-alkylidene-α,ß-unsaturated-γ-lactam system, can be classified into five skeletons including norpandamarilactonine, indolizinone, pandanamine, pandamarilactone, and pandamarilactonine. A plausible biosynthetic route toward 1-5, 7, and 9 is proposed.
Asunto(s)
Alcaloides/aislamiento & purificación , Alcaloides/metabolismo , Pandanaceae/química , Alcaloides/química , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/metabolismo , Furanos/química , Furanos/aislamiento & purificación , Furanos/metabolismo , Lactonas/química , Lactonas/aislamiento & purificación , Lactonas/metabolismo , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Componentes Aéreos de las Plantas/química , Hojas de la Planta/química , Pirrolidinas/química , Pirrolidinas/aislamiento & purificación , Pirrolidinas/metabolismo , Estereoisomerismo , TaiwánRESUMEN
BACKGROUND: Grape seeds extract (GSE) is a famous health food supplement for its antioxidant property. Different concentrations of GSE may have different impacts on cellular oxidative/reduction homeostasis. Antiproliferative effect of GSE has been reported in many cancers but rarely in oral cancer. METHODS: The aim of this study is to examine the antioral cancer effects of different concentrations of GSE in terms of cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial function, and DNA damage. RESULTS: High concentrations (50-400 µg/ml) of GSE dose-responsively inhibited proliferation of oral cancer Ca9-22 cells but low concentrations (1-10 µg/ml) of GSE showed a mild effect in a MTS assay. For apoptosis analyses, subG1 population and annexin V intensity in high concentrations of GSE-treated Ca9-22 cells was increased but less so at low concentrations. ROS generation and mitochondrial depolarization increased dose-responsively at high concentrations but showed minor changes at low concentrations of GSE in Ca9-22 cells. Additionally, high concentrations of GSE dose-responsively induced more γH2AX-based DNA damage than low concentrations. CONCLUSIONS: Differential concentrations of GSE may have a differentially antiproliferative function against oral cancer cells via differential apoptosis, oxidative stress and DNA damage.
Asunto(s)
Apoptosis/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Extracto de Semillas de Uva/uso terapéutico , Neoplasias de la Boca/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Vitis , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Extracto de Semillas de Uva/farmacología , Humanos , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno , SemillasRESUMEN
Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were determined by the interpretation of spectroscopic methods, especially NMR technologies (COSY, HSQC, HMBC, and NOESY). In addition, a convenient method for concentrating the alkylamide-rich fraction and analyzing fingerprint profile of A. oleracea was established.
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Amidas/química , Asteraceae/química , Extractos Vegetales/química , Flores/química , Estructura MolecularRESUMEN
Radiotherapy effectively destroys cancer cells in many sites of the body, but several limitations remain. This study investigated alternative splicing, which is a common mechanism of increased diversity in mRNAs and proteins. The relationships of alternative splicing to DNA damage and radiation such as UV and ionizing radiation were analyzed. The DNA damage responses of many genes involved in alternative splicing were compared between non-radiation and radiation treatments. Drugs that affect radioresistence or radiosensitization by modulating the effects of alternative splicing and radiation were also reviewed.
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Empalme Alternativo/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Preparaciones Farmacéuticas/administración & dosificación , Humanos , ARN Mensajero/genética , Tolerancia a Radiación/genéticaRESUMEN
The bone is the most common metastatic site of breast cancer. Bone metastasis causes pain, pathologic fractures, and severely reduces the quality of life. Breast cancer causes osteolytic bone metastasis, which is dependent on osteoclast-mediated bone resorption. While current treatments rely on palliative anti-resorptive agents, there is a need to develop a drug based on potential alternative therapies. This study is the first to determine that wedelolactone (WDL), a natural coumarin isolated from plants, can inhibit breast cancer-mediated osteoclastogenesis. Osteoclasts were generated from human CD14(+) monocytes cultured with M-CSF/RANKL and WDL suppressed human osteoclast differentiation and activity in vitro in a dose-dependent manner. Moreover, WDL inhibited the upregulation of osteoclasts stimulated by MDAMB231 breast cancer cells. The activity of WDL on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of Akt/mammalian target of the rapamycin signaling pathway (mTOR). Blocking Akt and mTOR by specific inhibitors significantly decreased osteoclast differentiation and bone resorption. Furthermore, WDL regulated breast cancer-enhanced interaction of osteoblasts and osteoclasts by decreasing M-CSF expression in MDAMB231-stimulated osteoblasts. Thus, this study suggests that WDL may be a potential natural agent for preventing and treating bone destruction in patients with bone metastasis due to breast cancer.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Cumarinas/administración & dosificación , Proteína Oncogénica v-akt/biosíntesis , Serina-Treonina Quinasas TOR/genética , Animales , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Macrófagos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Ligando RANK/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Many red algae-derived natural products are known to have anticancer effects. The biological functions of the red alga Solieria robusta from the Karachi coast (Pakistan) remain unclear. Here, we prepared a methanolic extracts of S. robusta (MESR) to examine its possible anti-oral cancer effects and the corresponding mechanism of action. Cell viability of MESR-incubated oral cancer Ca9-22 cells was dose-responsively decreased (p<0.001). According to a propidium iodide (PI)-based assay the cell cycle distribution was dramatically changed, especially for subG1 accumulation. Annexin V/PI assay of apoptosis using flow cytometry also showed that MESR-incubated Ca9-22 cells were dose-responsively increased (p<0.001). For evaluation of oxidative stress in MESR-incubated Ca9-22 cells, we found that reactive oxygen species (ROS) were overexpressed dose- and time-responsively and mitochondrial depolarization was also increased (p<0.001). Taken together, MESR showed inhibitory effects on oral cancer proliferation coupled with apoptosis and oxidative stress.
Asunto(s)
Antineoplásicos Fitogénicos , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Gingivales/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales , Rhodophyta/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Neoplasias Gingivales/metabolismo , Neoplasias Gingivales/patología , Humanos , Metanol/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This study is the first to demonstrate that parathyroid hormone-related protein (PTHrP), produced by human breast cancer cells after exposure to phthalate esters, contributes to bone metastasis by increasing osteoclastogenesis. This is also the first to reveal that obtusifolin reverses phthalate esters-mediated bone resorption. Human breast cancer cells were treated with dibutyl phthalate (DBP), harvested in conditioned medium, and cultured to osteoblasts or osteoclasts. Cultures of osteoblasts with DBP-MDA-MB-231-CM increased the osteoclastogenesis activator RANKL (receptor activator of nuclear factor κ-B ligand) and M-CSF (macrophage colony-stimulating factor). PTHrP was secreted in MDA-MB-231 cells. DBP-MDA-MB-231-CM reduced osteoblasts to produce osteoprotegerin, an osteoclastogenesis inhibitor, while DBP mediated PTHrP up-regulation, increasing IL-8 secretion in MDA-MB-231 and contributing to breast cancer-mediated osteoclast differentiation and bone resorption. Obtusifolin, a major bioactive compound present in Cassia tora L., suppressed phthalate esters-mediated bone resorption. Therefore, obtusifolin may be a novel anti-breast-cancer bone metastasis agent.
Asunto(s)
Antraquinonas/farmacología , Neoplasias Óseas/genética , Neoplasias Óseas/prevención & control , Medicamentos Herbarios Chinos/farmacología , Ésteres/efectos adversos , Proteína Relacionada con la Hormona Paratiroidea/genética , Ácidos Ftálicos/efectos adversos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Resorción Ósea , Cassia/química , Diferenciación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Factor Estimulante de Colonias de Macrófagos/metabolismo , Metástasis de la Neoplasia , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Ligando RANKRESUMEN
The methanolic extract of Flemingia macrophylla roots exhibited significant estrogenic activity in the transgenic plant assay system which was comparable to the activity of soybean extract. Utilizing estrogenic activity-guided fractionation, one new compound, fleminigin, together with 23 known compounds were isolated from F. macrophylla roots' methanolic extract. The structure of the new compound was identified based on intensive spectroscopic analysis and the full spectral data for one of the isolated compounds, flemichin E, was introduced for the first time in the current investigation. The estrogenic and anti-estrogenic activities of the isolated compounds were evaluated revealing that the isolated isoflavonoids may act as partial estrogen agonists, as well as antagonists. Additionally, the anti-inflammatory and the cytotoxic activities of the isolated compounds were studied. These results suggested the potential applications of F. macrophylla extract and its isolated compounds as selective estrogen receptor modulators (SERMs).
Asunto(s)
Antiinflamatorios/química , Fabaceae/química , Receptores de Estrógenos/metabolismo , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/toxicidad , Supervivencia Celular/efectos de los fármacos , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Conformación Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Receptores de Estrógenos/genética , Superóxidos/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
OBJECTIVE: Health related quality of life (HRQOL) is a multidimensional concept that is especially important for cancer patients with bone metastases, as maintaining and improving HRQOL is often the main focus of treatment. This study aims to determine factors that may influence HRQOL, which may in turn influence treatment and care of patients. METHODS: Patients (n=396) completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Bone Metastases module (BM22) at baseline. The EORTC QLQ-BM22 consists of four scales: painful site (PS), pain characteristics (PC), functional interference (FI), and psychosocial aspect (PA) scales. EORTC QLQ-BM22 data, together with sociodemographic and medical factors were analyzed by univariate analysis of variance (ANOVA). Items of significance were determined through backward selection, which were then put through multivariate analysis to determine further significance. RESULTS: Through ANOVA analysis, KPS>80 and breast primary histology were predictive of better HRQOL in the PS scale, while KPS>80, female gender, and breast primary histology were predictive of better HRQOL in the PC and FI scales. KPS>80 and prostate primary histology were predictive of better HRQOL in the PA scale. KPS>80 and primary cancer site were confirmed as significant predictive factors in multivariate analysis. RECOMMENDATIONS: This study identified baseline factors of gender, performance status, and primary histology as determinants of HRQOL in patients with bone metastases. Further study focusing on current treatment (chemotherapy, bisphosphonates, and radiotherapy) and spiritual well-being may identify additional factors affecting HRQOL. Understanding the influence of these factors will allow health care professionals to provide more effective palliative care.
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Neoplasias Óseas/psicología , Neoplasias/psicología , Cuidados Paliativos/métodos , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Neoplasias de la Mama/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias/patología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/psicología , Estudios Retrospectivos , Factores Sexuales , Perfil de Impacto de Enfermedad , Apoyo Social , Espiritualidad , Encuestas y CuestionariosRESUMEN
AIM: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells. MAIN METHODS: The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays. KEY FINDINGS: Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth. SIGNIFICANCE: WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.
Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Ciclohexanonas/farmacología , Flavonas/farmacología , Proteína Quinasa 14 Activada por Mitógenos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Extractos Vegetales/farmacología , Trasplante Heterólogo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Lawsonia inermis (Lythraceae) known as henna is one of the most popular and ancient plants used in cosmetics and hair dying. It is cultivated for its leaves but other parts such as seeds, flowers, stem bark and roots are also used in traditional medicine for millennia. Henna tattoo paste also proved to be beneficial for wound healing and in several skin diseases suggesting potent anti-inflammatory activity. To evaluate henna anti-inflammatory activity, 31 compounds, including three 1,5-diphenylpent-3-en-1-yne derivatives, lawsochylin A-C and three methyl naphthalene carboxylates, lawsonaphthoate A-C, were isolated from the stems and leaves of henna utilizing a bioassay-guided fractionation. The structures of the compounds were elucidated by spectroscopic data. Two compounds, lawsochylin A and lawsonaphthoate A showed potent anti-inflammatory activity by inhibition of superoxide anion generation (IC(50)=1.80 and 1.90 µg/ml) and elastase release (IC(50)=1.58 and 3.17 µg/ml) of human neutrophils in response to fMLP or cytochalasin B. Moreover, the known compounds, luteolin, apigenin, 4S-4-hydroxy-α-tetralone, and 2-butoxysuccinic acid, also showed potent inhibition of superoxide anion generation (IC(50)=0.75-1.78 µg/ml) and elastase release (IC(50)=1.62-3.61 µg/ml).
Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacología , Lawsonia (Planta)/química , Neutrófilos/efectos de los fármacos , Ácidos Carboxílicos/clasificación , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Naftalenos/química , Naftalenos/clasificación , Naftalenos/farmacología , Hojas de la Planta/química , Tallos de la Planta/químicaRESUMEN
INTRODUCTION: A primary ureteral stump tumor after a nephrectomy is rare; urothelial carcinoma of the ureteral stump after a nephrectomy for renal cell carcinoma is even rarer. A thorough review of the literature indicated that only seven cases have previously been reported. In this study, we report the first Taiwanese case of urothelial carcinoma of the ureteral stump after a nephrectomy. It is also the first female case in the literature. The relationship between inflammatory genes, medication history and ureteral stump carcinoma after a nephrectomy for renal cell carcinoma has not been reported. CASE PRESENTATION: A 72-year-old Asian Taiwanese women with chronic hepatitis C, liver cirrhosis and chronic kidney disease underwent a hand-assisted laparoscopic radical nephrectomy in 2001 due to renal cell carcinoma. Nine years later, she was diagnosed with ureteral stump urothelial carcinoma. Genetic and medication surveys were performed. Importantly, our patient had taken Chinese herbal drugs for more than 10 years and the inflammatory gene, Cox-2, was highly expressed in this patient. This is the first report to study the relationship between the Cox-2 gene and ureteral stump carcinoma after a nephrectomy for renal cell carcinoma. CONCLUSION: Long-term multiple use of Chinese herbal drugs could be one of the important risk factors for developing urothelial cancer. Close functional coupling between Chinese herbal drugs, Cox-2 gene activation and urothelial cancer should be further investigated.