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1.
Phytomedicine ; 128: 155413, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38513377

RESUMEN

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.


Asunto(s)
Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Neoplasias Gástricas , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Medicamentos Herbarios Chinos/farmacología , Ratones , Células Supresoras de Origen Mieloide/efectos de los fármacos , Línea Celular Tumoral , Ácidos Grasos Volátiles/metabolismo , Ratones Endogámicos BALB C , Humanos , ARN Ribosómico 16S , Masculino , Heces/microbiología , Femenino
2.
Medicine (Baltimore) ; 102(15): e33525, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37058027

RESUMEN

RATIONALE: Endometrial stromal sarcoma (ESS) is a rare malignant tumor. There is insufficient data supporting the efficiency of current treatments in multiple metastatic settings, and novel therapeutic options for ESS are considered an area of high unmet clinical need. PATIENT CONCERNS: We report the case of a 28-year-old woman who was diagnosed with ESS after undergoing total hysterectomy and left adnexectomy at another hospital. Two years later, the disease recurred, with multiple abdominal cavities and lung metastases. The patient was treated with a variety of chemotherapeutic drugs, including tyrosine kinase inhibitors, at the same hospital; however, none of them inhibited disease progression. DIAGNOSES: Computed tomography (CT) revealed multiple masses in the abdominal and pelvic cavities and multiple pulmonary nodules. Ultrasound-guided biopsy was performed and the tumor tissue was histologically confirmed after treatment. INTERVENTIONS: Insulin 300-400 IU was administrated by intravenous infusion in 10% glucose (500 mL) with disodium adenosine triphosphate 60 mg, coenzyme A 100 units, 10% potassium chloride 5 mL and 25% magnesium sulfate 5 mL. Dexamethasone (20-25 mg/d) was diluted with 10 mL of 2% lidocaine and then intraperitoneally injected after ascites draw. After 9 months, the patient was referred to another center for radiotherapy. OUTCOMES: CT images tomography showed recurrent pelvic masses, and multiple abdominal cavity and lung metastases gradually shrunk with treatment. Histological biopsy revealed growth arrest of tumor cells. The patient experienced for 3-years survival. LESSONS: High-dose insulin and dexamethasone combined with radiotherapy provides a novel and promising option for patients with multiple ESS metastases.


Asunto(s)
Neoplasias Endometriales , Hiperinsulinismo , Neoplasias Pulmonares , Sarcoma Estromático Endometrial , Femenino , Humanos , Adulto , Sarcoma Estromático Endometrial/radioterapia , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/diagnóstico , Insulina/uso terapéutico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundario , Dexametasona/uso terapéutico
4.
Acta Biomater ; 151: 588-599, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36002126

RESUMEN

Hepatocellular carcinoma (HCC) is a common high-mortality malignancy which still needs efficient treatments. HCC patients undergoing extrahepatic metastases are mostly with unsatisfactory prognosis. Therefore, specific attention has been paid to extrahepatic HCC metastasis. We integrated Sorafenib (Sor) and glucose oxidase (GOx) into a N-acetyl-galactosamine (GalNAc) modified zeolitic imidazolate framework (ZIF-8), designated as SG@GR-ZIF-8, for targeted bimodal therapies of chemotherapy and starvation therapy against HCC. The hepatic delivery of SG@GR-ZIF was mediated by the specific recognition of GalNAc residues with asialoglycoprotein (ASGPR) on the liver cell surface. Sor is a clinically approved anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. GOx can efficiently induce cell death and disturb malignant progression by suppressing glucose supply of cancer cells, which is highly associated with metabolic rewiring in metastasis. The nano-formulation exhibit significant anti-metastatic HCC activity against C5WN1 cells, a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In a subcutaneous C5WN1-tumor carrying mouse model, SG@GR-ZIF exhibits potent synergistic anti-tumor activity with a tumor inhibition rate of 89% and a prolonged survival status. The growth and pulmonary metastasis of HCC in an orthotopic mouse model of HCC was remarkably suppressed in SG@GR-ZIF treated group. The therapeutic strategy targeting energy supply combined with first-line treatment holds great promise for the future treatment of metastatic HCC. STATEMENT OF SIGNIFICANCE: SG@GR-ZIF, a N-acetyl-galactosamine modified metal-organic framework carrying Sorafenib and glucose oxidase, was fabricated for treating metastatic hepatocellular carcinoma (HCC). Sorafenib is an anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. Glucose oxidase blocks energy demand in HCC metastasis by depleting glucose. C5WN1 was used for therapeutic evaluations as a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In subcutaneous C5WN1-tumor bearing mice, SG@GR-ZIF exhibited a tumor inhibition rate of 89% and prolonged survival period. In orthotopic C5WN1-tumor carrying mice, the growth and pulmonary metastasis of hepatocarcinoma was remarkably suppressed by SG@GR-ZIF. Together, this study suggests the great potential of synergistic chemo/starvation therapy mediated by SG@GR-ZIF for treating metastatic HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Estructuras Metalorgánicas , Animales , Asialoglicoproteínas/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Galactosamina/uso terapéutico , Glucosa , Glucosa Oxidasa/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Células Madre Neoplásicas/patología , Sorafenib
5.
Clin J Gastroenterol ; 15(5): 960-967, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35834168

RESUMEN

We report a case in which multidisciplinary treatment was effective for hepatocellular carcinoma (HCC) with cranial and skeletal muscle metastases. A 55-year-old male with HCC received sorafenib for lung metastases. He was admitted to our hospital due to the skull metastasis detected by fluorodeoxyglucose positron emission tomography (FDG-PET). The patient underwent resection for skull metastasis. After the surgical treatment, he was treated with sorafenib again. Eight months after craniectomy, FDG-PET showed FDG uptake in the semimembranosus and semitendinosus muscles. Histopathological examination of the muscle biopsy revealed HCC muscle metastasis. Sorafenib treatment was discontinued. The investigational new drug (tegafur-gimeracil-oteracil) and tegafur-uracil were used for the treatment. These treatments proved to be ineffective as the lung metastases enlarged and new metastases appeared on the mediastinal lymph nodes and dura cava. The patient was unable to walk due to the enlarged thigh muscle metastases. Sorafenib was re-administered, which reduced the enlargement of the lung and mediastinal lymph nodes. Dural metastases were treated with resection and radiotherapy. Additional radiation therapy to the thigh muscles relieved the patient from pain experienced during walking. Sorafenib treatment was continued for the next 3 years. The patient survived for 4 years after the skull resection.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Drogas en Investigación/uso terapéutico , Fluorodesoxiglucosa F18/uso terapéutico , Humanos , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Cráneo/patología , Sorafenib/uso terapéutico , Tegafur/uso terapéutico
6.
Gan To Kagaku Ryoho ; 49(13): 1992-1994, 2022 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-36733068

RESUMEN

A 78-year-old man with advanced thoracic esophageal cancer underwent radical esophagectomy after neoadjuvant chemotherapy with cisplatin plus 5-FU. He had left adrenal metastasis 10 months after surgery and removed it, but 3 months later he had liver metastases. After 2 courses of chemotherapy with nedaplatin plus 5-FU, resection was performed. One course of nedaplatin plus 5-FU for adjuvant chemotherapy was added, but the patient was followed up without another chemotherapy after surgery because of intestinal obstruction due to infection and increase of the lymphatic cyst in the abdominal cavity. Six months after the liver resection, nodules appeared in the right lung, and 4 months later, multiple nodules extending to both lungs were observed. Therefore, it was judged that there were multiple lung metastases, and administration of nivolumab was started. He has been 3 years since the recurrence of esophageal cancer and 17 months after the start of nivolumab administration, but the recurrence lesion is only progressing to lung metastasis.


Asunto(s)
Neoplasias Esofágicas , Neoplasias Pulmonares , Masculino , Humanos , Anciano , Nivolumab/uso terapéutico , Fluorouracilo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/secundario , Esofagectomía
7.
J Nanobiotechnology ; 19(1): 428, 2021 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-34923976

RESUMEN

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.


Asunto(s)
Materiales Biocompatibles/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Molibdeno/química , Nanoestructuras/uso terapéutico , Óxidos/química , Animales , Materiales Biocompatibles/farmacocinética , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Ácido Fólico/química , Humanos , Hipertermia Inducida , Rayos Infrarrojos , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Ratones , Ratones Endogámicos BALB C , Nanoestructuras/química , Nanoestructuras/toxicidad , Polietilenglicoles/química , Albúmina Sérica Bovina/química , Ácido Tióctico/química , Distribución Tisular
8.
Adv Sci (Weinh) ; 8(21): e2101796, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34519180

RESUMEN

Prognosis and treatment of metastatic cancer continues to be one of the most difficult and challenging areas of oncology. Treatment usually consists of chemotherapeutics, which may be ineffective due to drug resistance, adverse effects, and dose-limiting toxicity. Therefore, novel approaches such as immunotherapy have been investigated to improve patient outcomes and minimize side effects. S100A9 is a calcium-binding protein implicated in tumor metastasis, progression, and aggressiveness that modulates the tumor microenvironment into an immunosuppressive state. S100A9 is expressed in and secreted by immune cells in the pre-metastatic niche, as well as, post-tumor development, therefore making it a suitable targeted for prophylaxis and therapy. In previous work, it is demonstrated that cowpea mosaic virus (CPMV) acts as an adjuvant when administered intratumorally. Here, it is demonstrated that systemically administered, S100A9-targeted CPMV homes to the lungs leading to recruitment of innate immune cells. This approach is efficacious both prophylactically and therapeutically against lung metastasis from melanoma and breast cancer. The current research will facilitate and accelerate the development of next-generation targeted immunotherapies administered as prophylaxis, that is, after surgery of a primary breast tumor to prevent outgrowth of metastasis, as well as, therapy to treat established metastatic disease.


Asunto(s)
Neoplasias de la Mama/patología , Calgranulina B/metabolismo , Comovirus/inmunología , Melanoma Experimental/patología , Nanopartículas/química , Animales , Neoplasias de la Mama/mortalidad , Calgranulina B/química , Línea Celular Tumoral , Comovirus/química , Femenino , Humanos , Inmunoterapia , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Macrófagos/citología , Macrófagos/inmunología , Macrófagos/metabolismo , Melanoma Experimental/mortalidad , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nanopartículas/metabolismo , Nanopartículas/uso terapéutico , Péptidos/química , Profilaxis Pre-Exposición , Tasa de Supervivencia
9.
Drug Deliv ; 28(1): 1923-1931, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34550040

RESUMEN

Transdermal drug delivery for local or systemic therapy provides a potential anticancer modality with a high patient compliance. However, the drug delivery efficiency across the skin is highly challenging due to the physiological barriers, which limit the desired therapeutic effects. In this study, we prepared liposome-in-hydrogels containing a tumor targeting photosensitizer IR780 (IR780/lipo/gels) for tumor photothermal therapy (PTT). The formulation effectively delivered IR780 to subcutaneous tumor and deep metastatic sites, while the hydrogels were applied on the skin overlying the tumor or on an area of distant normal skin. The photothermal antitumor activity of topically administered IR780/lipo/gels was evaluated following laser irradiation. We observed significant inhibition of the rate of the tumor growth without any toxicity associated with the topical administration of hydrogels. Collectively, the topical administration of IR780/lipo/gels represents a new noninvasive and safe strategy for targeted tumor PTT.


Asunto(s)
Hidrogeles/química , Indoles/farmacología , Liposomas/química , Fármacos Fotosensibilizantes/farmacología , Terapia Fototérmica/métodos , Administración Cutánea , Animales , Peso Corporal , Química Farmacéutica , Portadores de Fármacos/química , Indoles/administración & dosificación , Indoles/efectos adversos , Indoles/farmacocinética , Terapia por Luz de Baja Intensidad/efectos adversos , Terapia por Luz de Baja Intensidad/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/efectos adversos , Fármacos Fotosensibilizantes/farmacocinética , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Recent Pat Anticancer Drug Discov ; 16(2): 285-294, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34355688

RESUMEN

BACKGROUND: In recent years, there is an increasing interest in using Traditional Chinese Medicine (TCM) and their patents for the treatment of cancers. Qigefang (QGF) is a TCM formula and has been used for the treatment of metastatic esophageal cancer in China. However, its therapeutic effect on tumors and its mechanism of action is largely unknown. The aim of this study is to explore the role of QGF in the treatment of metastasis of Esophageal Squamous Cell Carcinoma( ESCC). METHODS: Human esophageal carcinoma cell line KYSE150 was used for this study. CCK-8 assay was used to determine the cytotoxicity of QGF. The KYSE150 cells were treated with QGF to determine its effect on cell migration (cell scratch assay and imaging) and invasion (Transwell system based with Matrigel assay). Western blotting was used to investigate the effect of QGF on relevant molecules of signaling pathways. A mouse model of lung metastasis of esophageal cancer was established by injecting the KYSE150-Luc cells through the tail vein. A small animal imaging system was used to observe tumor metastasis in the mice. RESULTS: QGF reduced cell migration and invasion of KYSE150 cells. QGF significantly inhibited lung metastasis in nude mice. Further study revealed that the expression of Growth arrest-specific 6 (Gas6), Anexelekto (Axl), N-Nuclear factor-kappa B (NF-κB) and matrix metalloproteinase-9 (MMP-9) proteins were decreased both in vitro and in vivo upon treatment with QGF. CONCLUSION: QGF could prevent invasion and metastasis of esophageal cancer by inhibiting the Gas6/Axl signaling pathway.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Movimiento Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/administración & dosificación , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/prevención & control , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Patentes como Asunto , Transducción de Señal/efectos de los fármacos
11.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34299130

RESUMEN

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.


Asunto(s)
Cisplatino/toxicidad , Frutas/química , Macrófagos/efectos de los fármacos , Melanoma Experimental/tratamiento farmacológico , Moraceae/química , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Animales , Antineoplásicos/toxicidad , Apoptosis , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Macrófagos/patología , Melanoma Experimental/inducido químicamente , Melanoma Experimental/patología , Potencial de la Membrana Mitocondrial , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Sustancias Protectoras/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Biomed Pharmacother ; 141: 111883, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34246955

RESUMEN

Lung metastasis of Triple-negative breast cancer (TNBC) causes severe breath-related events and poor prognosis. Ruyiping (RYP), a traditional Chinese medicine prescription, is used to treat breast cancer lung metastasis in clinical practice. This study was to explore the anti-lung-metastatic activities and mechanism of RYP extract by regulating macrophage polarization. The results showed that RYP can inhibit the viability and induce the apoptosis of TNBC cells. In in vitro experiments, RYP significantly inhibited the invasion and migration ability of TNBC cells promoted by M2, the subtype of macrophage which increased TNBC metastasis related genes. In in vivo experiments, RYP reduced the TNBC progression and lung metastasis. M2/M1 ration in the lung and M2 in the tumor was reduced by RYP, as well as M2 master regulator Stat6. Therefore, RYP extract may exhibit anti-lung metastasis function by reducing M2 in both tumor and lung through reducing Stat6.


Asunto(s)
Polaridad Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/patología , Macrófagos/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Neoplasias de la Mama Triple Negativas/patología , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Polaridad Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Macrófagos/fisiología , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
13.
Am J Chin Med ; 49(6): 1535-1555, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34247563

RESUMEN

Colorectal cancer (CRC) is the second most common cause of cancer death in the world, and metastatic CRC is a major cause of cancer death. Gallotannin (GT), a polyphenolic compound, has shown various biological effects such as anti-oxidant, anti-inflammatory, antimicrobial, and antitumor effects. However, the effects of GT on metastatic CRC cells are not completely understood. This study aimed to investigate the anti-metastatic effect of GT and the underlying mechanisms on metastatic CRC cells. Oral administration of GT suppressed the lung metastasis of metastatic CRC cells in the experimental mouse model. GT decreased the viability of metastatic CRC cell lines, including CT26, HCT116, and SW620, by inducing apoptosis through the activation of extrinsic and intrinsic pathways, cell cycle arrest through inactivation of CDK2/cyclin A complex, and autophagic cell death through up-regulation of LC3B and p62 levels. GT regulated PI3K/AKT/mTOR and AMPK signaling pathways, which are critical for the development and maintenance of cancer. Additionally, non-cytotoxic concentrations of GT can suppress migration and invasion of CRC cells by inhibiting the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and epithelial-mesenchymal transition by downregulating the expression of mesenchymal markers including snail, twist, and vimentin. In conclusion, GT prevented colorectal lung metastasis by reducing survival and inhibiting the metastatic phenotypes of CRC cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Taninos Hidrolizables/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Taninos Hidrolizables/química , Neoplasias Pulmonares/secundario , Ratones , Estructura Molecular
14.
Mol Nutr Food Res ; 65(15): e2100096, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34061433

RESUMEN

SCOPE: The beneficial effects of probiotics in reducing gastrointestinal inflammation and in preventing colorectal cancer have been reported, but the mechanism underlying the immunomodulatory effect of probiotics in inhibiting extra-intestinal tumor progression remains unclear. METHODS AND RESULTS: This study shows that probiotic supplementation attenuate lung metastasis of melanoma cells in mice. Feeding mice with VSL#3 probiotics change the composition and proportion of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Lachnospiraceae, Streptococcus, and Lachnoclostridium, are associated with the production of short-chain fatty acids in the gut. The concentrations of propionate and butyrate are upregulated in gut and blood after feeding VSL#3, and the increase in propionate and butyrate levels promotes the expression of chemokine (C-C motif) ligand 20 (CCL20) in lung endothelial cells and the recruitment of T helper 17 (Th17) cells to the lungs via the CCL20/chemokine receptor 6 axis. The recruitment of Th17 cells decreases the number of tumor foci in lungs and attenuates the lung metastasis of melanoma cells in mice. CONCLUSIONS: The results provide new information on the role and mechanisms of action of probiotics in attenuating extra-intestinal tumor metastasis.


Asunto(s)
Butiratos/metabolismo , Neoplasias Pulmonares/secundario , Melanoma Experimental/patología , Probióticos/farmacología , Propionatos/metabolismo , Animales , Quimiocina CCL20/metabolismo , Suplementos Dietéticos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal/fisiología , Neoplasias Pulmonares/dietoterapia , Neoplasias Pulmonares/patología , Ratones Endogámicos C57BL , Células Th17
15.
Medicine (Baltimore) ; 100(25): e26384, 2021 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-34160415

RESUMEN

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.


Asunto(s)
Adenoma Oxifílico/diagnóstico , Enfermedad de Graves/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Adenoma Oxifílico/complicaciones , Adenoma Oxifílico/secundario , Adenoma Oxifílico/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia con Aguja Fina , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Quimioradioterapia Adyuvante/métodos , Resultado Fatal , Enfermedad de Graves/complicaciones , Enfermedad de Graves/terapia , Humanos , Radioisótopos de Yodo/uso terapéutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Metástasis Linfática/diagnóstico , Metástasis Linfática/terapia , Masculino , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/secundario , Neoplasias del Mediastino/terapia , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/patología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/secundario , Neoplasias de la Tiroides/terapia , Tiroidectomía
16.
ACS Appl Mater Interfaces ; 13(22): 25701-25714, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34041901

RESUMEN

It has been a great challenge to simultaneously inhibit the outgrowth of both the primary tumor and metastasis in metastatic cancer treatment. Substantial studies have evidenced that the interaction of platelets and cancer cells supports tumor metastasis, and platelets are considered to have metastasis-targeting property. Inspired by injury-targeting and metastasis-targeting properties of platelets, we constructed a photothermal therapy strategy with activated platelet-targeting albumin-based nanoparticles, PSN-HSA-PTX-IR780, to amplify drug delivery in the primary tumor at mild temperatures and simultaneously inhibit metastasis via a "platelet bridge". Human serum albumin (HSA) was premodified with a P-selectin-targeting peptide (PSN peptide) or IR780 serving as a photosensitizer. Hybrid albumin nanoparticles were assembled via the disulfide reprogramming method and encapsulated paclitaxel (PTX) to formulate PSN-HSA-PTX-IR780. The PSN-modified albumin nanoparticles could bind with upregulated P-selectin on activated platelets and subsequently target cancer cells by using platelets as a "bridge". In addition, nanoparticle-generated hyperthermia induced tissue injury and increased tumor-infiltrating platelets, thereby recruiting more nanoparticles into the tumor in a self-promoted way. In vivo studies showed that the drug accumulation of PSN-HSA-PTX-IR780 was 2.86-fold higher than that of HSA-PTX-IR780 at the optimal temperature (45 °C), which consequently improved the therapeutic outcome. Moreover, PSN-HSA-PTX-IR780 also effectively targets and inhibits lung metastasis by binding with metastasis-infiltrating platelets. Altogether, the self-promoted nanoplatform provides a unique and promising strategy for metastatic cancer treatment with enhanced drug delivery efficacy.


Asunto(s)
Plaquetas/química , Neoplasias de la Mama/terapia , Hipertermia Inducida/métodos , Neoplasias Pulmonares/terapia , Nanopartículas/administración & dosificación , Paclitaxel/farmacología , Albúmina Sérica Humana/metabolismo , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Movimiento Celular , Proliferación Celular , Terapia Combinada , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Albúmina Sérica Humana/química , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
17.
ACS Appl Mater Interfaces ; 13(22): 25674-25684, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34042422

RESUMEN

Cooperative photothermal therapy (PTT) and photodynamic therapy (PDT) represents a promising strategy to conquer tumor with synergistic effect, while their long-term efficacy has been strictly limited by the multiple resistances of tumor. Here, we reported a core-shell nanoplatform for enhanced PTT/PDT combination against metastatic breast cancer. The nanosystem had photosensitizer chlorin e6 (Ce6) and rapamycin (RAP) pure drugs core and the polydopamine (PDA) shell, with surface PEGylation. Notably, we found that RAP was a highly robust sensitizer to boost the efficacy of both PTT and PDT by inhibiting the expression of heat shock protein 70 (HSP 70) and hypoxia inducible factor-1α (HIF-1α), respectively, resulting in cooperatively enhanced antitumor efficiency. Moreover, metastasis, the fatal risk of breast cancer, was also inhibited by virtue of RAP-mediated matrix metalloproteinases-2 (MMP-2) suppression. Upon intravenous injection, the nanosystem could passively accumulate into the tumor and impose potent phototherapies upon dual laser irradiations for complete tumor elimination and metastasis inhibition, giving rise to 100% mice survival over a long observation period. Collectively, this work offers a general solution to address the key limitations of tumor-resistant phototherapies and provides a highly promising nanoplatform for the management of metastatic cancer.


Asunto(s)
Neoplasias de la Mama/terapia , Movimiento Celular , Neoplasias Pulmonares/terapia , Nanopartículas/administración & dosificación , Fototerapia/métodos , Sirolimus/farmacología , Cicatrización de Heridas , Animales , Antibióticos Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Nanopartículas/química , Fármacos Fotosensibilizantes/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
18.
J Photochem Photobiol B ; 220: 112215, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34029847

RESUMEN

This work investigated the effect of photobiomodulation therapy (PBM) combined with radiotherapy (RT) on triple-negative breast cancer (TNBC)-bearing mice. Female BALB/c mice received 4 T1 cells into a mammary fat pad. Local RT was performed with a total dose of 60 Gy divided into 4 consecutive sessions of 15 Gy. For PBM, a red laser was used in three different protocols: i-) single exposure delivering 150 J.cm-2 (24 h after the last RT session), and ii-) radiant exposure of 150 J.cm-2 or iii-) fractionated radiant exposure of 37.5 J.cm-2 (after each RT session). Tumor volume, complete blood cell count, clinical condition, metastasis, and survival of animals were monitored during 3 weeks post-RT. Our results demonstrated that regardless of the protocol, PBM arrested the tumor growth, improved the clinical condition, and prevented hemolytic anemia. Besides, although PBM groups have exhibited a high neutrophil:lymphocyte ratio (NLR), they decreased the number of lung metastases and enhanced mouse survival. Worthy of note, PBM should be used along with the RT sessions in higher radiant exposures, since PBM at 150 J.cm-2 per session significantly extended the survival rate. Together, these data suggest PBM could be a potential ally to RT to fight TNBC.


Asunto(s)
Terapia por Luz de Baja Intensidad/métodos , Neoplasias de la Mama Triple Negativas/radioterapia , Animales , Femenino , Xenoinjertos , Humanos , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C
19.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33810045

RESUMEN

Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis; therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5IF4g/Luc BRAFV600E mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5IF4g/Luc melanoma growth in vitro and in a xenograft mouse model. DET and DETD-35 treatment inhibited A375LM5IF4g/Luc cell proliferation, and induced G2/M cell-cycle arrest and apoptosis. Furthermore, A375LM5IF4g/Luc exhibited clonogenic, metastatic and invasive abilities, and several A375LM5IF4g/Luc metastasis markers, N-cadherin, MMP2, vimentin and integrin α4 were significantly suppressed by treatment with either compound. Interestingly, DET- and DETD-35-induced Reactive Oxygen Species (ROS) generation and glutathione (GSH) depletion were found to be upstream events important for the in vitro activities, because exogenous GSH supplementation blunted DET and DETD-35 effects on A375LM5IF4g/Luc cells. DET and DETD-35 also induced mitochondrial DNA mutation, superoxide production, mitochondrial bioenergetics dysfunction, and mitochondrial protein deregulation. Most importantly, DET and DETD-35 inhibited lung metastasis of A375LM5IF4g/Luc in NOD/SCID mice through inhibiting pulmonary vascular permeability and melanoma cell (Mel-A+) proliferation, angiogenesis (VEGF+, CD31+) and EMT (N-cadherin) in the tumor microenvironment in the lungs. These findings indicate that DET and DETD-35 may be useful in the intervention of lung metastatic BRAFV600E mutant melanoma.


Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Asteraceae/química , Lactonas/aislamiento & purificación , Lactonas/farmacología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Apoptosis/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Inmunohistoquímica , Lactonas/química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Melanoma/patología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Proteínas Proto-Oncogénicas B-raf/genética , Especies Reactivas de Oxígeno/metabolismo , Sesquiterpenos/química , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Mol Cell Biochem ; 476(9): 3341-3351, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33929675

RESUMEN

Metastatic breast cancer remains a serious health concern and numerous investigations recommended medicinal plants as a complementary therapy. Crocin is one of the known anticancer bio-component. Recently, the inhibitory effect of metformin has been studied on the various aspects of cancer. However, no study reported their combination effects on metastatic breast cancer. In the present study, we have assessed their anti-metastatic effects on in vitro and in vivo breast cancer models. Using MTT assay, scratch, and adhesion tests, we have evaluated the cytotoxic, anti-invasive and anti-adhesion effects of crocin and metformin on 4T1 cell line, respectively. Their protective effects and MMP9 as well as VEGF protein expression levels (Western blotting) investigated in the 4T1 murine breast cancer model. Our results showed that both crocin and metformin reduced cell viability, delayed scratch healing and inhibited the cell adhesion, in vitro. While crocin alone restored the mice's weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation. These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Carotenoides/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/química , Metformina/farmacología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Apoptosis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/farmacología , Técnicas In Vitro , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
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