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1.
Clin Ter ; 172(3): 218-224, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33956041

RESUMEN

Background: Breast cancer is the most common malignancy dia-gnosed in women, and the incidence gradually increases. Magnetic resonance imaging (MRI) is become widely used to identify benign and malignant breast tumors. Objective: The aim of this study was to evaluate the relationships between apparent diffusion coefficient (ADC) values and histopathologic prognostic factors in breast cancer. Methods: Forty-nine breast carcinoma patients were included evaluated for prognostic factors, including histological type, histo-logical grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and molecular subtype. Minimum (ADCmin) and mean (ADCmean) ADC values were compared among prognostic factor groups by Mann-Whitney U test and Kruskal-Wallis test. Results: Lower mean ADCmin and ADCmean values were observed for no special type (NST) than for invasive lobular carcinoma (ILC) type (0.81 ± 0.03 × 10-3 and 0.96 ± 0.03 × 10-3 mm2/s, P= 0.002 and 0.03, respectively). The mean ADCmin and ADCmean values for the high-level Ki-67 group were significantly lower than those for the low-level Ki-67 group (P = 0.001 and 0.008, respectively). No correlations were observed between ADC values and histological grades, ER, PR, HER2, and molecular subtypes. Conclusion: ADCmin and ADCmean values correlated with the pro-liferation marker Ki-67 and histological grade. ADC values can serve as noninvasive indicators of cell proliferation in breast cancer.


Asunto(s)
Neoplasias de la Mama/patología , Imagen de Difusión por Resonancia Magnética/métodos , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos
2.
Gene ; 790: 145697, 2021 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-33964376

RESUMEN

Human Mitoribosomal Small Subunit unit (MRPS) family of genes appears to have role in cancer. Gene expression analysis of select MRPS genes (n = 9) in 15 cancer cell lines showed altered expression in cancer cells. Protein levels of MRPS6, MRPS23 showed significant overexpression in breast cancer cells and tissues. Interestingly, their overexpression did not correlate with mitochondrial ribosome translated COX2 protein levels in breast cancer. Subcellular fractionation analysis showed a distinct presence of MRPS23 in the nuclear fraction. GST/MRP6 and GST/MRPS23 pulldown assays identified 32 novel protein-protein interactions (PPIs) and MRPS23-RIPK3 interaction was validated. Co-expression module identification tool (CEMi) analysis of breast cancer gene expression and MRPS6 and MRPS23 interactions revealed hub interactions in gene expression modules having functional roles in cancer-associated cellular processes. Based on PPI network analysis a novel interaction MRPS23-p53 was validated. Knockdown of MRPS6 and MRPS23 decreased proliferation, expression of select mesenchymal markers, oncogenes, and increased expression of tumor suppressor genes. Taken together present study has revealed that MRPS6 and MRPS23 genes have pro-tumorigenic functions in breast cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinogénesis , Regulación Neoplásica de la Expresión Génica , Proteínas Mitocondriales/metabolismo , Ribosomas Mitocondriales/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Proliferación Celular , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Proteínas Mitocondriales/genética , Pronóstico , Células Tumorales Cultivadas
3.
Food Funct ; 12(9): 4046-4059, 2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-33977945

RESUMEN

Previous studies have reported that Portulaca oleracea L. polysaccharides (POL-P3b) is an immunoregulatory agent. However, few studies exist on POL-P3b as a novel immune adjuvant in combination with the DC vaccine for breast cancer treatment. In this work, a DC vaccine loaded with mouse 4T1 tumor cell antigen was prepared to evaluate the properties of POL-P3b in inducing the maturation and function of DC derived from mouse bone marrow, and then to investigate the effect of the DC vaccine combined with POL-P3b on breast cancer in vivo and in vitro. Morphological changes of DC were observed using scanning electron microscopy. Phenotypic and functional analyses of DC were detected by flow cytometry and allogeneic lymphocyte reaction. Cytokine levels in the DC culture supernatant were detected by ELISA. Western blotting analysis was used for the protein expression of TLR4, MyD88 and NF-κB. Apoptosis detection and protein expression of the tumor tissue were analyzed by TUNEL staining and immunohistochemistry, respectively. The security of POL-P3b was evaluated by the detection of hematological and blood biochemical indicators and pathological analysis for tissues. POL-P3b can induce DC activation and maturation, which is attributed to increasing the specific anti-tumor immune response, and the mechanism of action involved in the TLR4/MyD88/NF-κB signaling pathway. Experimental results in vivo further suggested that the administration of POL-P3b-treated antigen-primed DC achieved remarkable tumor growth inhibition through inducing apoptosis and enhancing immune responses. Moreover, the POL-P3b-treated DC vaccine was able to inhibit lung metastases. The results proved the feasibility of POL-P3b as an edible adjuvant of the DC vaccine for anti-breast cancer therapy.


Asunto(s)
Adyuvantes Inmunológicos , Neoplasias de la Mama/terapia , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/inmunología , Polisacáridos/inmunología , Portulaca/química , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/toxicidad , Animales , Antígenos de Neoplasias/inmunología , Apoptosis , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Inmunogenicidad Vacunal , Neoplasias Mamarias Experimentales/inmunología , Neoplasias Mamarias Experimentales/patología , Neoplasias Mamarias Experimentales/terapia , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Polisacáridos/toxicidad
4.
Medicine (Baltimore) ; 100(21): e26146, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34032767

RESUMEN

RATIONALE: Hormone therapies, particularly those targeting estrogen and its receptors, are a key treatment modality for patients with estrogen receptor (ER)-positive breast or ovarian cancer. Some gastric cancers (GCs) express ERs, and preclinical studies suggest the potential of estrogen-targeting hormone therapy on GC; however, the clinical relevance of this hormone therapy on GC treatment has not been well elucidated. PATIENT CONCERNS: An 80-year-old female was admitted to our department with hypogastric pain and vomiting. Computed tomography demonstrated small bowel obstruction, and laparotomy after bowel decompression revealed peritoneal dissemination consisting of a poorly-differentiated adenocarcinoma. Intestinal bypass between the ileum and transverse colon was performed. DIAGNOSES: The tumor was ER- and mammaglobin-positive, indicating that it originated from a breast cancer. Diagnostic imaging revealed no evidence of breast cancer; however, right axillary ER- and mammaglobin-positive lymphadenopathy was found. INTERVENTIONS: The patient received hormone therapy using letrozole based on a clinical diagnosis of occult breast cancer with peritoneal dissemination and right axillary lymph node metastasis. OUTCOMES: The patient remained disease free until 37 months but deceased at 53 months from the onset of disease. An autopsy revealed no tumor cells in the right breast tissue; however, there was a massive invasion of cancer cells in the stomach. LESSONS: A patient with ER positive GC with peritoneal dissemination and right axillary lymph node metastasis presented remarkable response to letrozole. The long-term survival obtained using letrozole for a patient with GC with distant metastasis suggests the potential of estrogen targeting hormone therapies for GC.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Letrozol/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Resultado Fatal , Femenino , Humanos , Metástasis Linfática , Receptores Estrogénicos/análisis , Neoplasias Gástricas/secundario
6.
Anticancer Res ; 41(5): 2383-2395, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952463

RESUMEN

BACKGROUND/AIM: This study aimed to investigate the effect of the new ciprofloxacin chalcone [7-(4-(N-substituted carbamoyl methyl) piperazin-1 yl)] on the proliferation, migration, and metastasis of MCF-7 and MDA-MB-231 breast cancer cell lines. MATERIALS AND METHODS: Cell viability, colony formation and cell migration abilities were analysed. Cell cycle distribution and apoptosis were examined by flow cytometry. The molecular mechanism underlying chalcone's activity was investigated using qRT-PCR and western blotting. RESULTS: This new ciprofloxacin chalcone significantly inhibited proliferation, colony formation, and cell migration abilities of both cancer cell lines. Furthermore, it initiated apoptosis and caused cell cycle arrest at G2/M and S phase in MCF-7 and MDA-MB-231 cell lines, respectively. In addition, it up-regulated the expression of pro-apoptotic factors, p53, PUMA and NOXA, and down-regulated the expression of anti-apoptotic factors, MDM2 and MDM4. At the same time, it inhibited epithelial-mesenchymal transition by increasing the expression of E-cadherin and decreasing the expression of TGF-ß1, SNAI1, TWIST1, MMP2, and MMP9. CONCLUSION: This new ciprofloxacin chalcone exhibited promising apoptotic and anti-metastatic activities against MCF-7 and MDA-MB-231 breast cancer cell lines, and, therefore, is an attractive molecule for drug development in the treatment of breast cancer.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Chalcona/farmacología , Ciprofloxacino/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Proteínas/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Cadherinas/genética , Cadherinas/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Chalcona/química , Ciprofloxacino/química , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Estructura Molecular , Proteínas/genética , Transducción de Señal/genética , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteína 1 Relacionada con Twist/genética , Proteína 1 Relacionada con Twist/metabolismo
7.
Adv Exp Med Biol ; 1187: 183-204, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33983579

RESUMEN

Owing to increased awareness of the importance of mammogram and advances in surgical technology, survival rate of patients with primary breast cancer has dramatically increased. Despite all these advances in breast cancer treatment, there are no currently available treatments for this disease once it metastasizes to distant organs including bones, lungs, brain, and liver. This is mainly attributed to the complexity of metastatic process. Recent advances in technology enabled cancer biologists to dissect each step of the metastatic process, and this led to discovery of major players and molecules in this process. In this section, we will discuss recent discovery and advances in the field of breast cancer metastasis research.


Asunto(s)
Neoplasias de la Mama , Mama , Neoplasias de la Mama/patología , Humanos , Pulmón/patología , Metástasis de la Neoplasia/patología
8.
Anticancer Res ; 41(5): 2689-2696, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952500

RESUMEN

BACKGROUND/AIM: The COVID-19 lockdown includes restrictive measures and temporary health system reorganization. Resources were shifted to COVID-19 patients, screening programs were temporary suspended, and oncological care suffered slow-down. The aim of the study was to evaluate the impact of these measures on breast cancer patients. PATIENTS AND METHODS: All breast cancer patients referred to our unit from February 21, 2019 to February 21, 2021 were enrolled. Type of treatments and surgery, TNM, tumor diameter, and predictive and prognostic factors were analyzed. RESULTS: Out of 445 patients with a breast cancer diagnosis, 182 (40.9%) were enrolled in the COVID-19 group (from February 21, 2010 to February 21, 2021). These patients were compared with 263 (59.1%) patients pre-COVID-19. Tumor diameters were bigger in the COVID-19 group. Type of surgery and N staging were statistically significantly different. Extreme advanced disease incidence was significantly different between the groups (2.7% COVID-19 group vs. 0 pre-COVID-19 group, p=0.011). Incidence of post-surgical radiation-therapy was higher in the COVID-19 group. Other variables analyzed were comparable without a statistically significant difference. CONCLUSION: COVID-19 led to increased tumor dimensions, advanced N-staging, and increased need for adjuvant treatments in breast cancer.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , /epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , /psicología , Terapia Combinada , Femenino , Humanos , Incidencia , Metástasis Linfática , Masculino , Mastectomía , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Tiempo de Tratamiento , Carga Tumoral
9.
Nat Commun ; 12(1): 2666, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33976222

RESUMEN

Tumor necrosis happens commonly in advanced solid tumors. We reported that necroptosis plays a major role in tumor necrosis. Although several key necroptosis regulators including receptor interacting protein kinase 1 (RIPK1) have been identified, the regulation of tumor necroptosis during tumor development remains elusive. Here, we report that Z-DNA-binding protein 1 (ZBP1), not RIPK1, mediates tumor necroptosis during tumor development in preclinical cancer models. We found that ZBP1 expression is dramatically elevated in necrotic tumors. Importantly, ZBP1, not RIPK1, deletion blocks tumor necroptosis during tumor development and inhibits metastasis. We showed that glucose deprivation triggers ZBP1-depedent necroptosis in tumor cells. Glucose deprivation causes mitochondrial DNA (mtDNA) release to the cytoplasm and the binding of mtDNA to ZBP1 to activate MLKL in a BCL-2 family protein, NOXA-dependent manner. Therefore, our study reveals ZBP1 as the key regulator of tumor necroptosis and provides a potential drug target for controlling tumor metastasis.


Asunto(s)
Neoplasias de la Mama/genética , Necroptosis/genética , Proteínas de Unión al ARN/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Células HEK293 , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Noqueados , Ratones Desnudos , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Proteínas de Unión al ARN/metabolismo , Tratamiento con ARN de Interferencia/métodos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
10.
Nat Commun ; 12(1): 2788, 2021 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-33986289

RESUMEN

Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.


Asunto(s)
Neoplasias de la Mama/patología , Carcinogénesis/patología , Efrina-A4/metabolismo , Células Madre Neoplásicas/patología , Ribonucleasa Pancreática/metabolismo , Antígeno AC133/metabolismo , Animales , Neoplasias de la Mama/genética , Carcinogénesis/genética , Línea Celular , Femenino , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Unión Proteica/genética , Ribonucleasa Pancreática/sangre , Ribonucleasa Pancreática/genética , Resultado del Tratamiento
11.
Nat Commun ; 12(1): 2954, 2021 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-34012010

RESUMEN

How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3' flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3' nuclease, excises flaps at the immediate 3' end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.


Asunto(s)
Neoplasias de la Mama/metabolismo , Replicación del ADN/fisiología , Endonucleasas de ADN Solapado/metabolismo , Oxidorreductasas Intramoleculares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular , ADN/química , ADN/metabolismo , Daño del ADN , ADN Polimerasa III/genética , ADN Polimerasa III/metabolismo , Replicación del ADN/genética , Femenino , Endonucleasas de ADN Solapado/deficiencia , Endonucleasas de ADN Solapado/genética , Técnicas de Inactivación de Genes , Inestabilidad Genómica , Células HCT116 , Humanos , Oxidorreductasas Intramoleculares/deficiencia , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/deficiencia , Factores Inhibidores de la Migración de Macrófagos/genética , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Conformación de Ácido Nucleico , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Fase S , Especificidad por Sustrato
12.
Molecules ; 26(9)2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33947079

RESUMEN

Breast cancer is still one of the leading causes of mortality in the female population. Despite the campaigns for early detection, the improvement in procedures and treatment, drastic improvement in survival rate is omitted. Discovery of aquaporins, at first described as cellular plumbing system, opened new insights in processes which contribute to cancer cell motility and proliferation. As we discover new pathways activated by aquaporins, the more we realize the complexity of biological processes and the necessity to fully understand the pathways affected by specific aquaporin in order to gain the desired outcome-remission of the disease. Among the 13 human aquaporins, AQP3 and AQP5 were shown to be significantly upregulated in breast cancer indicating their role in the development of this malignancy. Therefore, these two aquaporins will be discussed for their involvement in breast cancer development, regulation of oxidative stress and redox signalling pathways leading to possibly targeting them for new therapies.


Asunto(s)
Acuaporina 3/metabolismo , Acuaporina 5/metabolismo , Neoplasias de la Mama/metabolismo , Oxidación-Reducción , Animales , Antioxidantes/metabolismo , Acuaporina 3/genética , Acuaporina 5/genética , Biomarcadores , Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Susceptibilidad a Enfermedades , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Familia de Multigenes , Estrés Oxidativo
13.
Medicine (Baltimore) ; 100(18): e25545, 2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-33950928

RESUMEN

BACKGROUND: Breast cancer is a common malignant tumor in women. In recent years, its incidence is increasing year by year, and its morbidity and mortality rank the first place among female malignant tumors. Some key enzymes and intermediates in glycolysis are closely related to tumor development. Pyruvate kinase M2 (PKM2) is an important rate-limiting enzyme in glycolysis pathway. Meanwhile, it is highly expressed in proliferative cells, especially in tumor cells, and plays an important role in the formation of Warburg effect and tumorigenesis. Previous studies have explored the effects of PKM2 expression on the prognosis and clinical significance of breast cancer patients, while the results are contradictory and uncertain. This study uses controversial data for meta-analysis to accurately evaluate the problem. We collected relevant Oncomine and The Cancer Genome Atlas (TCGA) data to further verify the results. Through bioinformatics analysis, the mechanism and related pathways of PKM2 in breast cancer are explored. METHODS: We searched Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases from inception to March 2021. The language restrictions are Chinese and English. The published literatures on PKM2 expression and prognosis or clinicopathological characteristics of breast cancer patients were statistically analyzed. Combined hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (95% CIs) were used to evaluate the effects of PKM2 on the prognosis and clinicopathological features of breast cancer. Stata 14.0 software was applied for meta-analysis. Oncomine and TCGA databases were used to meta-analyze the differences of PKM2 mRNA expression between breast cancer and normal breast tissues. The expression of PKM2 protein was verified by Human Protein Atlas (HPA) database. The relationship between the gene and the survival of breast cancer patients was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). The relationship between PKM2 gene and clinicopathological characteristics was analyzed by using LinkedOmics, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis was performed by using Metascape. Protein-protein interaction (PPI) network was constructed by String website. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study provides high-quality medical evidence for the correlation between the expression of PKM2 and the prognosis and clinicopathological features of breast cancer. Through bioinformatics analysis, this study further deepens the understanding of the mechanism and related pathways of PKM2 in breast cancer. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W52HB.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/mortalidad , Mama/patología , Carcinogénesis/patología , Proteínas Portadoras/metabolismo , Proteínas de la Membrana/metabolismo , Hormonas Tiroideas/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Proteínas Portadoras/análisis , Biología Computacional , Supervivencia sin Enfermedad , Femenino , Humanos , Proteínas de la Membrana/análisis , Metaanálisis como Asunto , Pronóstico , Medición de Riesgo/métodos , Hormonas Tiroideas/análisis
14.
Medicine (Baltimore) ; 100(18): e25835, 2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-33950995

RESUMEN

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Productos Biológicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Vesículas Extracelulares/metabolismo , Microbioma Gastrointestinal , Antineoplásicos Hormonales/uso terapéutico , Productos Biológicos/uso terapéutico , Neoplasias de la Mama/patología , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Femenino , Humanos , Klebsiella pneumoniae/citología , Klebsiella pneumoniae/metabolismo , Células MCF-7 , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , Orina/citología
15.
Medicine (Baltimore) ; 100(18): e25880, 2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-33951002

RESUMEN

ABSTRACT: Whether breast-conserving therapy (BCT) should be chosen as a local treatment for young women with early-stage breast cancer is controversial. This study compared the survival benefits of BCT or mastectomy in young women under 40 with early-stage breast cancer and further explored age-stratified outcomes. This study investigated whether there is a survival benefit when young women undergo BCT compared with mastectomy.The characteristics and prognosis of white women under 40 with stage I-II breast cancer from 1988 to 2016 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. These women were either treated with BCT or mastectomy. The log-rank test of the Kaplan-Meier survival curve and Cox proportional risk regression model were used to analyze the data and survival. The analysis was stratified by age (18-35 and 36-40 years).A total of 23,810 breast cancer patients were included, of whom 44.9% received BCT and 55.1% underwent mastectomy, with a median follow-up of 116 months. Patients undergoing mastectomy had a higher tumor burden and younger age. By the end of the 20th century, the proportion of BCT had grown from nearly 35% to approximately 60%, and then gradually fell to 35% into the 21st century. Compared with the mastectomy group, the BCT group had improved breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.917; 95% CI, 0.846-0.995, P = .037) and overall survival (OS) (HR 0.925; 95% CI, 0.859-0.997, P = .041). In stratified analysis according to the different ages, the survival benefit of BCT was more pronounced in the slightly older (36-40 years) group while there was no significant survival difference in the younger group (18-35 years).In young women with early-stage breast cancer, BCT showed survival benefits that were at least no worse than mastectomy, and these benefits were even better in the 36 to 40 years age group. Young age may not be a contraindication for BCT.


Asunto(s)
Neoplasias de la Mama/cirugía , Toma de Decisiones Clínicas , Mastectomía Segmentaria/estadística & datos numéricos , Mastectomía/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Mama/patología , Mama/cirugía , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Contraindicaciones de los Procedimientos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Mastectomía Segmentaria/efectos adversos , Estadificación de Neoplasias , Pronóstico , Medición de Riesgo/estadística & datos numéricos , Programa de VERF/estadística & datos numéricos , Resultado del Tratamiento , Carga Tumoral , Adulto Joven
16.
Int J Nanomedicine ; 16: 3059-3071, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33953555

RESUMEN

Purpose: This study aimed to explain the influence of zein nanosphere (ZN NS) formulation on the pharmacotherapeutic profile of PTS in MCF7 cells. Methods: Liquid-liquid phase separation was used to formulate PTS-ZN NSs. The formulations developed were evaluated for particle-size analysis, encapsulation efficiency, and in vitro diffusion. Also, assays of cytotoxicity, uptake, cell-cycle progression, annexin V, apoptotic gene mRNA expression and biochemical assays were carried out. Results: The PTS-ZN NS formulation selected showed 104.5±6.2 nm, 33.4±1.8 mV, 95.1%±3.6%, and 89.1%±2.65% average particle size, zeta-potential, encapsulation efficiency and in vitro diffusion, respectively. With MCF7 cells, IC50 was reduced approximately 15-fold, with increased cellular uptake, accumulation in the G2/M phase, increased percentage of cells in the pre-G1 phase, amelioration of early and late apoptosis, raised mRNA expression of CASP3 and CASP7, lower expression of cyclin-CDK1, and enhanced oxidant potential through decreased glutathione reductase (GR) activity, and enhanced reactive oxygen-species generation and lipid-peroxidation products. Conclusion: PTS-ZN NSs indicated enhanced antiproliferative, proapoptotic, and oxidant potential toward MCF7 cells compared to free PTS. Ameliorated results of nanosized carriers, cellular uptake, and sustained diffusion may contribute to these outcomes.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Nanocompuestos/química , Estilbenos/química , Estilbenos/farmacología , Zeína/química , Antineoplásicos/química , Antineoplásicos/farmacología , Humanos , Células MCF-7 , Oxidantes/química , Oxidantes/farmacología , Oxidación-Reducción , Tamaño de la Partícula
17.
Anticancer Res ; 41(5): 2473-2476, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952473

RESUMEN

BACKGROUND/AIM: During surgery for patients with known, diffuse metastatic bone disease (MBD), lesional tissue is routinely sent for pathological evaluation. However, there are limited data to assess whether there is a role for histopathology for MBD despite time and cost of interpretation, as well as whether a positive sample changes the subsequent treatment course. PATIENTS AND METHODS: Sixty-six cases from 2017 to 2020 were reviewed retrospectively. The median age at surgery was 63.5 years (range of 23 to 84 years), and the primary tumor was most frequently breast (24.2%, n=16), renal (21.2%, n=14) or lung (15.2%, n=10). The most common location of MBD was the femur (60.6%, n=40). RESULTS: The overall yield of a positive tissue sample of MBD was 77.3% (n=51). The positive rate from sending intramedullary reamings was 65.4% (n=17 of 26). Among the 66 cases (63 patients), a change in the subsequent clinical management was recorded in 9.1% (n=6). The most common change was related to the medication regimen (n=5), with one change related to recognition of the carcinoma origin via histology, which was previously unknown. CONCLUSION: Despite the routine practice of sending tissue for histology during surgery for known and diffuse MBD, a change in the subsequent clinical management is uncommon. Prior to sending tissue, surgeons should discuss this practice with the multidisciplinary care team on a per-patient basis.


Asunto(s)
Enfermedades Óseas/cirugía , Neoplasias de la Mama/cirugía , Fémur/cirugía , Neoplasias Renales/cirugía , Neoplasias Pulmonares/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Óseas/diagnóstico por imagen , Enfermedades Óseas/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Fémur/diagnóstico por imagen , Fémur/patología , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Resultado del Tratamiento
18.
Anticancer Res ; 41(5): 2489-2494, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952476

RESUMEN

BACKGROUND/AIM: Most patients with breast cancer are assigned to radiotherapy, which may cause fears leading to sleep disorders. Very few data are available regarding the prevalence of sleep disorders and corresponding risk factors. PATIENTS AND METHODS: Data of 175 patients with breast cancer presenting for adjuvant radiotherapy were retrospectively analyzed. Twenty-three patient and tumor characteristics were investigated for associations with pre-radiotherapy sleep disorders. RESULTS: Seventy-eight patients (44.6%) stated sleep disorders prior to radiotherapy. These were significantly associated with higher distress score (p<0.0001); greater number of emotional (p<0.0001), physical (p<0.0001) or practical problems (p<0.001); and request for psycho-oncological support (p<0.001). Trends were found for worse performance status (p=0.062) and higher comorbidity index (p=0.059). CONCLUSION: Sleep disorders prior to radiotherapy for breast cancer are common. This applies particularly to patients with risk factors including distress due to emotional, physical or practical problems. These patients should be offered psycho-oncological support as soon as possible.


Asunto(s)
Neoplasias de la Mama/radioterapia , Radioterapia Ayuvante/efectos adversos , Trastornos del Sueño-Vigilia/radioterapia , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/patología
19.
Anticancer Res ; 41(5): 2697-2709, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952501

RESUMEN

BACKGROUND/AIM: Prior studies have underlined the prognostic relevance of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer. However, an accurate demonstration of treatment efficacy is dependent on its potential to predict long-term outcomes of recurrence and death, and this issue remains somewhat controversial. PATIENTS AND METHODS: One hundred and sixty-nine patients with breast cancer (BC) treated with NAC followed by surgery were enrolled in this retrospective study. After carrying out multivariable analyses, involving baseline characteristics (tumor stage, nodal status, histological grade, biological profile) and response status, we analysed the association between pCR and disease-free (DFS) and overall survival (OS) in various subtypes. Moreover, we investigated several residual disease-scoring combinations to check whether they could discriminate prognostic subsets according to their variable tumor range after NAC. RESULTS: Overall, factors associated with pCR were non-luminal subtype (p<0.001), high grade (p=0.001) and HER2-overexpression (p=0.001). Residual tumor and nodal stage after NAC significantly correlated with DFS (p=0.007) and OS (p<0.001). Similarly, pCR after NAC showed significantly better DFS (p=0.01), particularly for HER2-positive (p=0.003), triple-negative (p=0.019) and HER2-positive Luminal B profiles (p=0.019). However, there was no statistical difference in the OS among patients who had PCR, compared to absence of pCR (p=0.40). CONCLUSION: Extent of residual disease and evidence of regression provide helpful prognostic details in BC patients treated with NAC. Achieving pCR after NAC is related with significantly better DFS, with the potential of maximized breast and axillary conservation based on clinical response. The distribution of expertise in a cross-disciplinary setting could provide safe and favourable prognosis, while improving cosmetic outcomes and quality of life.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptor ErbB-2/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología
20.
BMJ Open ; 11(5): e043642, 2021 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-34006546

RESUMEN

OBJECTIVE: Estimation of the net survival of breast cancer helps in assessing breast cancer burden at a population level. Thus, this study aims to estimate the net survival of breast cancer at different cancer staging and age at diagnosis in the east coast region of West Malaysia. SETTING: Kelantan, Malaysia. PARTICIPANTS: All breast cancer cases diagnosed in 2007 and 2011 identified from Kelantan Cancer Registry. DESIGN: This retrospective cohort study used a relative survival approach to estimate the net survival of patients with breast cancer. Thus, two data were needed; breast cancer data from Kelantan Cancer Registry and general population mortality data for Kelantan population. PRIMARY AND SECONDARY OUTCOME MEASURES: Net survival according to stage and age group at diagnosis at 1, 3 and 5 years following diagnosis. RESULTS: The highest net survival was observed among stage I and II breast cancer cases, while the lowest net survival was observed among stage IV breast cancer cases. In term of age at diagnosis, breast cancer cases aged 65 and older had the best net survival compared with the other age groups. CONCLUSION: The age at diagnosis had a minimal impact on the net survival compared with the stage at diagnosis. The finding of this study is applicable to other populations with similar breast cancer profile.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Preescolar , Humanos , Lactante , Malasia/epidemiología , Estadificación de Neoplasias , Sistema de Registros , Estudios Retrospectivos
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