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1.
Klin Lab Diagn ; 66(3): 147-153, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33793113

RESUMEN

A study of interleukin-6 (IL-6), hepcidin-25 (GP-25) was conducted in 22 patients with breast cancer before neoadjuvant chemotherapy and in 27 healthy women in the control group. Significant expression of the GP-25 protein was revealed in breast cancer patients, compared to control. The rates were high both in patients with anemic sindrome (AS) and without it (p <0.01). Latent iron deficiency, AS, IDA and functional iron deficiency (FJ) were more often detected in patients with stage III disease. A significant difference in the parameters of GP-25 and IL-6 was noted, the indicators were higher in patients with stage III (p <0.01). No close correlation was found between IL-6, GP-25 and other acute-phase proteins (FR, CRP) at the initial stages of AS formation. On the contrary, a positive correlation was observed in patients with IDA and FJ between IL-6 and all acute-phase proteins (GP-25, FR, CRP). However, a small number of observations do not allow an unambiguous conclusion about the role of IL-6 and GP-25 expression in the development of AS in cancer patients with breast cancer and requires further study.


Asunto(s)
Anemia Ferropénica , Neoplasias de la Mama , Anemia Ferropénica/complicaciones , Anemia Ferropénica/tratamiento farmacológico , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Ferritinas , Hepcidinas , Humanos , Interleucina-6/genética , Terapia Neoadyuvante
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 279-285, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33829703

RESUMEN

Objective: The deep learning method was used to automatically segment the tumor area and the cell nucleus based on needle biopsy images of breast cancer patients prior to receiving neoadjuvant chemotherapy (NAC), and then, the features of the cell clusters in the tumor area were identified to predict the level of pathological remission of breast cancer after NAC. Methods: 68 breast cancer patients who were to receive NAC at Jiangsu Province Hospital were recruited and the hematoxylin-eosin (HE) stained preoperative biopsy sections of these patients were collected. Unet++ was used to establish a segmentation model and the tumor area and nucleus of the needle biopsy images were automatically segmented accordingly. Then, according to the nuclei in the automatically segmented tumor area, the features of the cells in the tumor were constructed. After that, effective features were selected through the feature selection method and the classifier model was constructed and trained with five-fold cross validation to predict the degree of post-NAC pathological remission. Results: Predictions were made based on the needle biopsy images of the 68 patients. The model that combined the 10-dimensional features selected with the minimal redundancy-maximum-relevancy approach (mRMR) and training with the random forest (RF) classifier had the highest prediction accuracy, reaching 82.35%, and an area under curve ( AUC) value of 0.908 2. Conclusion: This model automatically segments tumor areas and cell nucleus on the biopsy images. The features of the cell clusters which are analyzed and identified in the tumor area can be used to predict the pathological response of the patient to NAC. The method is reliable and replicable. In addition, we found that the textural features of cells in the tumor area was a useful predictor of patient response to NAC, which further confirmed that cell cluster in the tumor area is of great significance to the prediction of treatment outcome.


Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Biopsia con Aguja , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Resultado del Tratamiento
3.
Anticancer Res ; 41(4): 2193-2195, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813433

RESUMEN

BACKGROUND/AIM: Since January 2020, coronavirus disease (COVID-19) cases have been confirmed in Japan, and the number of patients with COVID-19 has been increasing. Two emergency declarations have been made previously and one is currently in effect. Based on our experience of a situation that could affect cancer treatment, this study retrospectively examined the correlation between perioperative anticancer therapy and COVID-19 incidence in patients with breast cancer. PATIENTS AND METHODS: Patients who underwent perioperative anticancer therapy for breast cancer at our hospital from February 2020 to February 2021 were included in this study. The presence or absence of COVID-19, timing of anticancer drug initiation, and clinical data were collected. RESULTS: No cases of COVID-19 were diagnosed in patients receiving perioperative anticancer therapy at our hospital. CONCLUSION: Regimen modification, active use of supportive care, and patient lifestyle were factors reducing the incidence of COVID-19.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama , Atención Perioperativa/métodos , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante/estadística & datos numéricos , Terapia Combinada , Femenino , Humanos , Huésped Inmunocomprometido , Incidencia , Japón/epidemiología , Persona de Mediana Edad , Terapia Neoadyuvante/estadística & datos numéricos , Atención Perioperativa/efectos adversos , Atención Perioperativa/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , /fisiología
4.
Anticancer Res ; 41(4): 1793-1802, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813384

RESUMEN

BACKGROUND/AIM: Human epidermal growth factor receptor 2 (HER2) P95-isoform could be involved in trastuzumab resistance in HER2 metastatic breast cancer. MATERIALS AND METHODS: A total of 114 metastatic breast cancer patients treated with trastuzumab were evaluated retrospectively. HER2 was centrally reviewed. P95 was evaluated along with other markers possibly affecting trastuzumab efficacy in regards to progression-free survival and overall survival. RESULTS: HER2 was centrally negative in 54 cases. P95 expression was significantly higher in HER2-positive tumors. High p95 was associated with gain of HER2 copy number variations (CNVs), high pHER2Tyr877, Ki67 and HER2 mRNA. P95 as a continuous variable was positively correlated with mRNA expression of HER2 and negatively correlated with HER4 and IGF1. HER2-negative p95-high patients had a marginally higher risk for death (HR=2.15, p=0.055). CONCLUSION: p95 was associated with higher HER2 CNVs and mRNA expression, pHER2Tyr877 expression and high Ki67, indicating a more aggressive phenotype.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Isoenzimas , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Metástasis de la Neoplasia , Supervivencia sin Progresión , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios Retrospectivos
5.
Gan To Kagaku Ryoho ; 48(3): 440-442, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790181

RESUMEN

When the primary breast cancer disappears by neoadjuvant chemotherapy, it is often difficult to detect it during the breast preserving surgery. Before neoadjuvant chemotherapy, preoperative nipple-side HydroMARK-marking, which was made of titanium coil and hydrogel, was a very useful and effective method because of its fine detection by ultrasonography. We report a case of 51-year-old female with the triple negative breast cancer(TNBC). At first, the HydroMARK was inserted between the nipple and the tumor. Its distance was about 10 mm toward the nipple. EC therapy followed by docetaxel was performed for 6 months as neoadjuvant chemotherapy. After that, her left TNBC(T1N0M0, Stage Ⅰ, invasive ductal carcinoma, ER[-], PgR[-], HER2[-])was disappeared in all imagings and resected in August 2018. The HydroMARK was clearly detected by intraoperative ultrasonography and her right breast preserving surgery was completely performed. Its pathological finding was pCR(pathological complete response).


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Neoplasias de la Mama Triple Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/cirugía , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Pezones/cirugía , Receptor ErbB-2 , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/cirugía
6.
Gan To Kagaku Ryoho ; 48(3): 446-448, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790183

RESUMEN

Five patients with gastric metastasis from breast cancer were treated in our hospital. About the histopathological types of primary breast cancer, 4 patients were invasive ductal carcinomas and 1 was invasive lobular carcinoma. One patient was found by gastrointestinal fiberscopy for a detailed examination of her high CEA, 2 for stenosis, 1 for bleeding and 1 for epigastralgia. After the diagnosis of gastric metastasis, 2 patients were treated with chemotherapies, 1 with hormone therapy and 2 with palliative treatments. One of them was treated with gastroduodenal stenting for pyloric stenosis, but she was died by bleeding from gastric lesion. Based on the results, constriction and bleeding with gastric metastasis is considered to be severe condition in the treatment of metastatic breast cancer.


Asunto(s)
Neoplasias de la Mama , Carcinoma Lobular , Neoplasias Gástricas , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Neoplasias Gástricas/tratamiento farmacológico
7.
Gan To Kagaku Ryoho ; 48(3): 452-454, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790185

RESUMEN

The purpose of our study was to test the efficacy and toxicity of palbociclib therapy for breast cancer treatment. Ten patients diagnosed with breast carcinoma were selected for this retrospective study between 2017 and 2018. After the patients had previously been administered palbociclib, they received either capecitabine or eribulin. As a result, the median PFS of capecitabine and eribulin were 6.4 months(3-10)and 5.8 months(4-7), respectively. Therefore, the treatment administered after palbociclib therapy may be useful for breast cancer patients.


Asunto(s)
Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Humanos , Piperazinas/uso terapéutico , Posmenopausia , Piridinas , Receptor ErbB-2 , Estudios Retrospectivos
8.
Gan To Kagaku Ryoho ; 48(3): 455-456, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790186

RESUMEN

Breast cancer patient(invasive ductal carcinoma, ER[+], PgR[+], HER2[3+], Ki-67: 30%)had neoadjuvant chemotherapy( FEC followed by docetaxel plus trastuzumab). After surgical operation(mastectomy and Ax)was performed and she received trastuzumab plus hormone therapy. After 2 years later, she had liver metastasis that showed IDC, ER(+), PgR (+), HER2(-). In addition, BRCA positive was shown. Therefore, the patient received olaparib tablets(300 mg twice daily). After 2 months later, liver metastasis reduced dramatically.


Asunto(s)
Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Terapia Neoadyuvante , Ftalazinas , Piperazinas , Receptor ErbB-2 , Trastuzumab/uso terapéutico
9.
Nat Commun ; 12(1): 1786, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33741974

RESUMEN

The majority of breast cancers express the estrogen receptor (ERα) and agents targeting this pathway represent the main treatment modality. Endocrine therapy has proven successful in the treatment of hormone-responsive breast cancer since its early adoption in the 1940s as an ablative therapy. Unfortunately, therapeutic resistance arises, leading to disease recurrence and relapse. Recent studies increased our understanding in how changes to the chromatin landscape and deregulation of epigenetic factors orchestrate the resistant phenotype. Here, we will discuss how the epigenome is an integral determinant in hormone therapy response and why epigenetic factors are promising targets for overcoming clinical resistance.


Asunto(s)
Neoplasias de la Mama/genética , Epigénesis Genética , Epigenómica/métodos , Regulación Neoplásica de la Expresión Génica , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Recurrencia Local de Neoplasia , Receptores Estrogénicos/metabolismo
10.
Ther Umsch ; 78(3): 136-144, 2021 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-33775135

RESUMEN

Outpatient breast cancer treatment after the hospital: what's next? - Adjuvant medical therapies, management of side effects and common fears, planing and coordination of optimal follow-up care in view of current guidelines Abstract. Following successful breast cancer surgery patients will generally be facing a certain prolonged period of medical treatment accompanied by several years of follow-up care, usually in the setting of a private practice or outpatient clinic. These medical treatments, which have proven by evidence to substantially reduce the risk of breast cancer recurrence and thereby significantly added to the boost in overall prognosis of this disease, are discussed in the light of current international treatment guidelines in this article. The standard approach to modern medical therapies is outlined on the basis of clinical pathological risk factors and tumor biology for different breast cancer subtypes (e. g. luminal, HER2-positiv, triple negativ / basal-like) accordingly. We hereby focus particularly upon the management of therapy-induced side effects, typical substance-specific toxicities as well as offering remedy to common fears and myths concerning medical breast cancer treatment. Last but not least we describe our perspective of the "ideal outpatient follow-up care", outlining a time-plan, implementing interdisciplinary expertise and stressing the necessity for good teamwork and interaction among all health care specialists involved, to optimise patient comfort and outcome.


Asunto(s)
Neoplasias de la Mama , Cuidados Posteriores , Neoplasias de la Mama/tratamiento farmacológico , Miedo , Hospitales , Humanos , Recurrencia Local de Neoplasia/terapia , Pacientes Ambulatorios
11.
Molecules ; 26(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652854

RESUMEN

(2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , MicroARNs/genética , Antineoplásicos/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Curcumina/análogos & derivados , Curcumina/farmacología , Ciclohexanonas/farmacología , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7
12.
Molecules ; 26(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652957

RESUMEN

Multidrug resistance (MDR) remains a major problem in cancer therapy and is characterized by the overexpression of p-glycoprotein (P-gp) efflux pump, upregulation of anti-apoptotic proteins or downregulation of pro-apoptotic proteins. In this study, an Apolipoprotein A1 (ApoA1)-modified cationic liposome containing a synthetic cationic lipid and cholesterol was developed for the delivery of a small-molecule chemotherapeutic drug, doxorubicin (Dox) to treat MDR tumor. The liposome-modified by ApoA1 was found to promote drug uptake and elicit better therapeutic effects than free Dox and liposome in MCF-7/ADR cells. Further, loading Dox into the present ApoA1-liposome systems enabled a burst release at the tumor location, resulting in enhanced anti-tumor effects and reduced off-target effects. More importantly, ApoA1-lip/Dox caused fewer adverse effects on cardiac function and other organs in 4T1 subcutaneous xenograft models. These features indicate that the designed liposomes represent a promising strategy for the reversal of MDR in cancer treatment.


Asunto(s)
Apolipoproteína A-I/química , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Apolipoproteína A-I/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Células MCF-7 , Polietilenglicoles/química , Polietilenglicoles/farmacología
13.
Molecules ; 26(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652969

RESUMEN

Cytotoxic flavonoids of Murraya tetramera were investigated in this study. A novel flavonoid and twelve known flavonoids, including seven flavones (1-7), three flavanones (8-10), and three chalcones (11-13) were isolated from the leaves and twigs of Murraya tetramera. Chemical structures were elucidated by NMR combined with MS spectral analysis, and the new compound (6) was confirmed as 3',5'-dihydroxy-5,6,7,4'-tetramethoxyflavone. Furthermore, all the isolated flavonoids were evaluated for their cytotoxicities against murine melanoma cells (B16), and human breast cancer cells (MDA-MB-231) by CCK-8 assay. Among them, compounds 7, 13, and 5 exhibited potent cytotoxic activities against B16 cell lines (IC50 = 3.87, 7.00 and 8.66 µg/mL, respectively). Compounds 5, 13, and 12 displayed potent cytotoxicities against MDA-MB-231 cell lines (IC50 = 3.80, 5.95 and 7.89 µg/mL, respectively). According to the correlation of the structure and activity analysis, 5-hydroxyl and 8-methoxyl substituents of the flavone, 8-methoxyl substituent of the flavanone, and 3',5'-methoxyl substituents of the chalcone could be critical factors of the high cytotoxicity. The results indicated that the active flavonoids have potential to be developed as leading compounds for treating cancers.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Flavonoides/farmacología , Murraya/química , Animales , Antineoplásicos Fitogénicos/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chalconas/química , Chalconas/farmacología , Femenino , Flavonoides/química , Humanos , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Ratones , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química
14.
Int J Nanomedicine ; 16: 1943-1960, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727808

RESUMEN

Introduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC. Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99mTc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors. Results: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls. Conclusion: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Portadores de Fármacos/química , Nanopartículas/química , Radiofármacos/química , Receptor ErbB-2/metabolismo , Dióxido de Silicio/química , Tecnecio/química , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Endocitosis , Femenino , Fluoresceína-5-Isotiocianato/química , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Polietilenglicoles/química , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico , Proteoma/metabolismo , Proteómica , Radiofármacos/farmacocinética , Tecnecio/farmacocinética , Distribución Tisular/efectos de los fármacos , Tomografía Computarizada de Emisión de Fotón Único , Resultado del Tratamiento
15.
Int J Nanomedicine ; 16: 1961-1976, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727809

RESUMEN

Introduction: Metastatic breast cancer seriously harms women's health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects. Methods: The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds. Results: The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis. Conclusion: The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Nanopartículas/química , ARN Interferente Pequeño/administración & dosificación , Dióxido de Silicio/química , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/farmacología , Preparaciones de Acción Retardada/uso terapéutico , Doxorrubicina/farmacología , Portadores de Fármacos/química , Endocitosis/efectos de los fármacos , Femenino , Células HEK293 , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/ultraestructura , Invasividad Neoplásica , Metástasis de la Neoplasia , Oxidación-Reducción , Porosidad , ARN Interferente Pequeño/farmacología , Distribución Tisular/efectos de los fármacos
16.
Zhonghua Wai Ke Za Zhi ; 59(3): 222-227, 2021 Mar 01.
Artículo en Chino | MEDLINE | ID: mdl-33685057

RESUMEN

Objective: To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer. Methods: Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison. Results: Patients who received trastuzumab-based therapy(n=294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab(n=177) (84.4% vs. 72.4%, χ²=4.095, P=0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P>0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ²=5.340, P=0.021), but they had similar OS (91.4% vs. 89.1%, χ²=1.008, P=0.315). Conclusions: TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carboplatino/administración & dosificación , Docetaxel/administración & dosificación , Femenino , Humanos , Estudios Retrospectivos , Trastuzumab/administración & dosificación
17.
Life Sci ; 274: 119354, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33737087

RESUMEN

AIMS: Gigantol is a bibenzyl compound isolated from orchids of the genus Dendrobium. Gigantol has been demonstrated to possess various pharmacologic (including anticancer) effects. Cisplatin (DDP) has been used and studied as the first-line agent for breast cancer (BC) treatment. Often, its efficacy is jeopardized due to intolerance and organ toxicity. We investigated if gigantol could enhance the anticancer effects of DDP in BC cells and its underlying mechanism of action. MAIN METHODS: The potential pathway of gigantol in BC cells was detected by network-pharmacology and molecular-docking studies. The proliferation and apoptosis of BC cell lines were measured by the MTT assay, colony formation, Hoechst-33342 staining, and flow cytometry. Protein expression was measured by western blotting. KEY FINDINGS: Gigantol could inhibit proliferation of BC cells and enhance DDP-induced apoptosis. According to the results of western blotting, gigantol reinforced DDP-induced anticancer effects through downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in BC cells. The effects were consistent with those of the pathway inhibitor LY294002. SIGNIFICANCE: Our data might provide new insights into the underlying antitumor effect of gigantol in BC cells. This enhancement effect in the combination of gigantol and DDP may provide many therapeutic benefits in clinical treatment regimens against BC.


Asunto(s)
Bibencilos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Cisplatino/farmacología , Sinergismo Farmacológico , Guayacol/análogos & derivados , Fosfatidilinositol 3-Quinasas/química , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Guayacol/farmacología , Humanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Células Tumorales Cultivadas
18.
Anticancer Res ; 41(3): 1243-1250, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788715

RESUMEN

BACKGROUND/AIM: Breast cancer (BC) may be affected by diabetes and anti-diabetic medication, as well as its therapeutic agents. Low-dose metronomic chemotherapy (LDMC) is an available treatment option in BC. We investigated the impact of insulin on low-dose metronomic vinorelbine and mafosfamide in BC cell lines. MATERIALS AND METHODS: Human BC cell lines T-47D, MCF-7, MDA-MB-231, BT-549 and non-tumorigenic breast cell line MCF-10A were exposed to 0.01 µg/ml and 10 µg/ml insulin in combination with low-dose metronomic vinorelbine or mafosfamide. The cell viability was determined after 24-72 hours using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: Insulin, especially at a concentration of 10 µg/ml, seemed to increase viability of vinorelbine-treated hormone receptor-positive BC cells, whereas low-dose mafosfamide treatment tended to be potentiated by insulin in triple-negative cells. CONCLUSION: Our findings suggest that insulin may influence the cytotoxic activity of LDMC depending on insulin concentration, type of cytotoxic drug used and BC cell line.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/análogos & derivados , Insulina/farmacología , Vinorelbina/administración & dosificación , Administración Metronómica , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ciclofosfamida/administración & dosificación , Femenino , Humanos
19.
Int J Nanomedicine ; 16: 1473-1485, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33654397

RESUMEN

Purpose: The near-infrared fluorescent dye indocyanine green (ICG) has shown great potential in the photodynamic therapy (PDT) and photothermal therapy (PTT) of cancer. However, its disadvantages of instability in aqueous solution, short half-life, and non-targeting accumulation limit the effectiveness of ICG PDT/PTT. To overcome the disadvantages of ICG in tumor treatment, we designed PEGylated-human serum albumin (PHSA)-ICG-TAT. In this nanoparticle, PEG4000, the HSA package, and nuclear targeting peptide TAT (human immunodeficiency virus 1 [HIV-1]-transactivator protein) were used to improve the water solubility of ICG, prolong the life span of ICG in vivo, and target the nuclei of tumor cells, respectively. Methods: The PHSA-ICG-TAT was characterized in terms of morphology and size, ultraviolet spectrum, dispersion stability, singlet oxygen and cellular uptake, and colocalization using transmission electron microscopy and dynamic light scattering, and fluorescence assay, respectively. Subsequently, the anti-tumor effect of PHSA-ICG-TAT was investigated via in vitro and in vivo experiments, including cell viability, apoptosis, comet assays, histopathology, and inhibition curves. Results: The designed ICG-loaded nanoparticle had a higher cell uptake rate and stronger PDT/PTT effect than free ICG. The metabolism of PHSA-ICG-TAT in normal mice revealed that there was no perceptible toxicity. In vivo imaging of mice showed that PHSA-ICG-TAT had a good targeting effect on tumors. PHSA-ICG-TAT was used for the phototherapy of tumors, and significantly suppressed the tumor growth. The tumor tissue sections showed that the cell gap and morphology of the tumor tissue had been obviously altered after treatment with PHSA-ICG-TAT. Conclusion: These results indicate that the PHSA-ICG-TAT had a significant therapeutic effect against tumors.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Núcleo Celular/metabolismo , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dispersión Dinámica de Luz , Femenino , Fluorescencia , Colorantes Fluorescentes/química , Humanos , Verde de Indocianina/química , Ratones Endogámicos BALB C , Nanopartículas/ultraestructura , Fármacos Fotosensibilizantes/farmacología , Polietilenglicoles/química , Albúmina Sérica Humana/química
20.
Int J Nanomedicine ; 16: 1487-1508, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33654398

RESUMEN

Breast cancer stem cells (BCSCs), also known as breast cancer initiating cells, are reported to be responsible for the initiation, progression, therapeutic resistance, and relapse of breast cancer. Conventional therapeutic agents mainly kill the bulk of breast tumor cells and fail to eliminate BCSCs, even enhancing the fraction of BCSCs in breast tumors sometimes. Therefore, it is essential to develop specific and effective methods of eliminating BCSCs that will enhance the efficacy of killing breast tumor cells and thereby, increase the survival rates and quality of life of breast cancer patients. Despite the availability of an increasing number of anti-BCSC agents, their clinical translations are hindered by many issues, such as instability, low bioavailability, and off-target effects. Nanosized drug delivery systems (NDDSs) have the potential to overcome the drawbacks of anti-BCSC agents by providing site-specific delivery and enhancing of the stability and bioavailability of the delivered agents. In this review, we first briefly introduce the strategies and agents used against BCSCs and then highlight the mechanism of action and therapeutic efficacy of several state-of-the-art NDDSs that can be used to treat breast cancer by eliminating BCSCs.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Células Madre Neoplásicas/patología , Tamaño de la Partícula , Femenino , Humanos , Transducción de Señal
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