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1.
Cancer Epidemiol ; 90: 102573, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692143

RESUMEN

BACKGROUND: Statins are a group of lipid-lowering drugs with pleiotropic effects that include, but are not limited to the inhibition of cholesterol synthesis resulting in a wide range of anti-inflammatory, anti-tumor, immunomodulatory, and anti-thrombotic properties. This study aimed to determine the impact of the prior to- or after- breast surgery usage of statins on the tumor prognosis in breast cancer (BC) patients. METHODS: A cohort of patients diagnosed with early invasive ductal BC (n=301) at the Hospital Italiano de Buenos Aires, Argentina, with a minimum follow-up period of 10 years after the surgical procedure were included and stratified according to the time of use of statins and type of statin used. Then, local relapse-free survival (RFS), metastasis-free survival (MFS), bone metastasis-free survival (BMFS), visceral metastasis-free (VMFS), mixed metastasis (bone and visceral)-free survival (mix-MFS) and overall survival (OS) were analyzed. RESULTS: Statins usage after breast surgery was related with lesser metastatic occurrence (p=0.017), lower number of metastatic foci (p=0.034) and fewer dead events (p=0.041), as well as longer MFS (p=0.013) and OS (p=0.027). When stratified by the nature of statins (hydrophilic or lipophilic), only the relatively hydrophilic statin rosuvastatin (ROSU) had an impact on the increase of MFS and OS (p=0.018 and p=0.030, respectively). CONCLUSION: Post-surgery statins usage was associated with increased MFS and OS, with increased benefits of ROSU over simvastatin (SIM) or atorvastatin (ATOR). These results set the rationale for additional studies addressing the use of statins, and particularly, rosuvastatin, to improve the outcome of BC patients.


Asunto(s)
Neoplasias de la Mama , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Persona de Mediana Edad , Anciano , Pronóstico , Argentina/epidemiología , Mastectomía , Estudios de Seguimiento , Adulto , Estudios Retrospectivos , Carcinoma Ductal de Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/mortalidad , Tasa de Supervivencia
2.
ACS Appl Bio Mater ; 7(5): 3154-3163, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38695332

RESUMEN

ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.


Asunto(s)
Neoplasias de la Mama , Quempferoles , Ensayo de Materiales , Nanopartículas , Silicio , beta-Galactosidasa , Humanos , beta-Galactosidasa/metabolismo , Silicio/química , Células MCF-7 , Nanopartículas/química , Quempferoles/química , Quempferoles/farmacología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Tamaño de la Partícula , Colorimetría , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Femenino , Estructura Molecular
3.
Aust J Gen Pract ; 53(5): 305-310, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38697062

RESUMEN

BACKGROUND: Oestrogen deprivation is the mainstay of treatment for women with hormone receptor-positive breast cancer, but unfortunately it causes multiple side effects that can significantly impair quality of life. Genitourinary symptoms are very common and although these symptoms can be effectively managed with vaginal oestrogens, concerns about their safety in women with breast cancer limits their use. OBJECTIVE: The aim of this review is to provide a summary of the data on the safety of vaginal oestrogens in women with breast cancer to help general practitioners advise their patients in this situation. DISCUSSION: Although there are no large randomised prospective studies to assess safety, the current evidence suggests reassurance can be provided to the majority of women with a history of breast cancer considering vaginal oestrogens. Consultation with the oncology team is advised for women taking aromatase inhibitors, where the safety of vaginal oestrogens is less certain.


Asunto(s)
Neoplasias de la Mama , Estrógenos , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/complicaciones , Estrógenos/uso terapéutico , Estrógenos/efectos adversos , Administración Intravaginal , Enfermedades Urogenitales Femeninas/tratamiento farmacológico , Enfermedades Urogenitales Femeninas/fisiopatología , Calidad de Vida/psicología
4.
Breast Dis ; 43(1): 93-98, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38701136

RESUMEN

BACKGROUND: Breast cancer (BC) cases in Makassar, Indonesia, are on the rise, with 2723 cases recorded in 2018. Tumor cells in the blood indicate metastasis, emphasizing the need for early diagnosis and monitoring. Pleiotrophin (PTN) is associated with various human malignancies, and recent studies suggest a correlation between PTN expression and advanced BC stages; therefore, PTN could serve as an independent predictor of metastasis. This study aimed to determine the correlation between serum PTN level, histopathological grading, and metastasis occurrence in BC patients in Makassar, Indonesia. METHODS: This study used an observational cross-sectional design. Pleiotrophin serum levels were examined using enzyme-linked immunosorbent assays. This study used a t-test and ROC curve analysis for the statistical tests. RESULTS: Of the 64 samples used in this study, metastasis was present in 26 cases and absent in 38 samples. The mean PTN serum levels in metastatic and non-metastatic breast cancer patients were 4.311 and 1.253, respectively. The PTN receiver operating characteristic curve showed an area under the curve of 2.47 ng/dL, which was statistically significant (p < 0.001). A significant relationship was found between PTN level and metastasis (p < 0.001). The correlation coefficient was 0.791, indicating a positive correlation. CONCLUSION: This study revealed that the serum PTN level among breast cancer patients had a cut-off value of 2.47 ng/dL. The research established a clear correlation between PTN level and metastasis occurrence in breast cancer patients, indicating a higher likelihood of distant metastasis with elevated PTN concentration.


Asunto(s)
Neoplasias de la Mama , Proteínas Portadoras , Citocinas , Humanos , Femenino , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Citocinas/sangre , Proteínas Portadoras/sangre , Persona de Mediana Edad , Estudios Transversales , Adulto , Biomarcadores de Tumor/sangre , Anciano , Curva ROC , Indonesia/epidemiología , Metástasis de la Neoplasia
5.
Cytokine ; 179: 156632, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38701734

RESUMEN

The study was planned to evaluate the differences in certain proinflammatory cytokines(IL-6, TNF-α) with CRP and biochemical parameters (E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid), between women with pre- and postmenopausal breast cancer and seemingly healthy women in Iraqi women as controls; at medical city in teaching Oncology hospital,70 breast cancer patients women their ages ranged (47.51 ± 1.18) and 20 healthy women with age (44.45 ± 2.66) begun from September (2020) to February (2021). The aims of this study to investigate the evaluation of chemotherapy effects especially doxorubicin and cyclophosphamide only use in this study in pre and postmenopausal breast cancer women on proinflammatory cytokines(IL-6, TNF-α) with CRP and on biochemical parameters(E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid) in pre and postmenapausal breast cancer women. The patients were divided into five groups and each group contains 14 patients women with breast cancer during pre and postmenopausal periods. The control groups were divided into 10 pre and 10 postmenopausal women(Fig. 1). The results of proinflammatory cytokines of and biochemical parameters in premenopausal groups were as the levels of IL-6 (pg/ml),TNF-α(pg/ml) and CRP (ng/ml) showed significant increase differences (P < 0.01)among breast cancer treated (BCT) groups in comparison with control groups,While the Liver enzymes GGT,LDH and TSB showed highly significant increase (P < 0.01) in BCT groups, Estrogen levels (pg/ml) and D3(ng/ml) increased significantly (P < 0.01)among BCT groups. Blood serum calcium and phosphorus with uric acid levels (mg/dl) showed significant difference (P < 0.01); While the result in postmenopausal of IL-6(pg/ml), TNF-α (pg/ml) and CRP (ng/ml) showed highly significant differences (P < 0.01)among BCT groups.While GGT(IU/L), LDH(IU/L) and TSB (mg/dl) enzymes were increased significantly (p < 0.01), Estrogen (pg/ml) and D3(ng/ml) levels showed significant increase (P < 0.01) among BCT groups.Blood calcium and phosphorus showed significant increase (P < 0.01) while uric acid was non-significant increase (P > 0.05).


Asunto(s)
Neoplasias de la Mama , Citocinas , Posmenopausia , Humanos , Femenino , Neoplasias de la Mama/sangre , Posmenopausia/sangre , Persona de Mediana Edad , Citocinas/sangre , Adulto , Premenopausia/sangre , Factor de Necrosis Tumoral alfa/sangre , Interleucina-6/sangre , Proteína C-Reactiva/metabolismo , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico
6.
BMJ Open ; 14(5): e081660, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702085

RESUMEN

INTRODUCTION: Breast cancer survivors have an increased risk for chronic fatigue and altered gut microbiota composition, both with negative health and quality of life affects. Exercise modestly improves fatigue and is linked to gut microbial diversity and production of beneficial metabolites. Studies suggest that gut microbiota composition is a potential mechanism underlying fatigue response to exercise. Randomised controlled trials testing the effects of exercise on the gut microbiome are limited and there is a scarcity of findings specific to breast cancer survivors. The objective of this study is to determine if fitness-related modifications to gut microbiota occur and, if so, mediate the effects of aerobic exercise on fatigue response. METHODS AND ANALYSIS: The research is a randomised controlled trial among breast cancer survivors aged 18-74 with fatigue. The primary aim is to determine the effects of aerobic exercise training compared with an attention control on gut microbiota composition. The secondary study aims are to test if exercise training (1) affects the gut microbiota composition directly and/or indirectly through inflammation (serum cytokines), autonomic nervous system (heart rate variability) or hypothalamic-pituitary-adrenal axis mediators (hair cortisol assays), and (2) effects on fatigue are direct and/or indirect through changes in the gut microbiota composition. All participants receive a standardised controlled diet. Assessments occur at baseline, 5 weeks, 10 weeks and 15 weeks (5 weeks post intervention completion). Faecal samples collect the gut microbiome and 16S gene sequencing will identify the microbiome. Fatigue is measured by a 13-item multidimensional fatigue scale. ETHICS AND DISSEMINATION: The University of Alabama at Birmingham Institutional Review Board (IRB) approved this study on 15 May 2019, UAB IRB#30000320. A Data and Safety Monitoring Board convenes annually or more often if indicated. Findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04088708.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Fatiga , Microbioma Gastrointestinal , Humanos , Femenino , Supervivientes de Cáncer/psicología , Persona de Mediana Edad , Adulto , Anciano , Ensayos Clínicos Controlados Aleatorios como Asunto , Ejercicio Físico/fisiología , Calidad de Vida , Terapia por Ejercicio/métodos , Adulto Joven , Adolescente
7.
Biomed Phys Eng Express ; 10(4)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38714180

RESUMEN

Radiotherapy (RT) is one of the major treatment modalities among surgery and chemotherapy for carcinoma breast. The surface dose study of modified reconstructive constructive Mastectomy (MRM) breast is important due to the heterogeneity in the body contour and the conventional treatment angle to save the lungs and heart from the radiation. These angular entries of radiation beam cause an unpredictable dose deposition on the body surface, which has to be monitored. Thermoluminescent dosimeter (TLD) or optically stimulated luminescent dosimeter (nano OSLD) are commonly preferable dosimeters for this purpose. The surface dose response of TLD and nano OSLD during MRM irradiation has been compared with the predicted dose from the treatment planning system (TPS). The study monitored 100 MRM patients by employing a total 500 dosimeters consisting of TLD (n = 250) and nano OSLD (n = 250), during irradiation from an Elekta Versa HD 6 MV Linear accelerator. The study observed a variance of 3.9% in the dose measurements for TLD and 3.2% for nano OSLD from the planned surface dose, with a median percentage dose of 44.02 for nano OSLD and 40.30 for TLD (p value 0.01). There was no discernible evidence of variation in dose measurements attributable to differences in field size or from patient to patient. Additionally, no variation was observed in dose measurements when comparing the placement of the dosimeter from central to off-centre positions. In comparison, a minor difference in dose measurements were noted between TLD and nano OSLD, The study's outcomes support the applicability of both TLD and nano OSLD as effective dosimeters during MRM breast irradiation for surface dose evaluation.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Dosificación Radioterapéutica , Dosimetría Termoluminiscente , Humanos , Femenino , Dosimetría Termoluminiscente/métodos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Planificación de la Radioterapia Asistida por Computador/métodos , Dosimetría con Luminiscencia Ópticamente Estimulada/métodos , Persona de Mediana Edad , Dosis de Radiación , Adulto , Mama/efectos de la radiación , Mama/cirugía
8.
Biosens Bioelectron ; 258: 116347, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38723332

RESUMEN

Monitoring drug efficacy is significant in the current concept of companion diagnostics in metastatic breast cancer. Trastuzumab, a drug targeting human epidermal growth factor receptor 2 (HER2), is an effective treatment for metastatic breast cancer. However, some patients develop resistance to this therapy; therefore, monitoring its efficacy is essential. Here, we describe a deep learning-assisted monitoring of trastuzumab efficacy based on a surface-enhanced Raman spectroscopy (SERS) immunoassay against HER2-overexpressing mouse urinary exosomes. Individual Raman reporters bearing the desired SERS tag and exosome capture substrate were prepared for the SERS immunoassay; SERS tag signals were collected to prepare deep learning training data. Using this deep learning algorithm, various complicated mixtures of SERS tags were successfully quantified and classified. Exosomal antigen levels of five types of cell-derived exosomes were determined using SERS-deep learning analysis and compared with those obtained via quantitative reverse transcription polymerase chain reaction and western blot analysis. Finally, drug efficacy was monitored via SERS-deep learning analysis using urinary exosomes from trastuzumab-treated mice. Use of this monitoring system should allow proactive responses to any treatment-resistant issues.


Asunto(s)
Biomarcadores de Tumor , Técnicas Biosensibles , Neoplasias de la Mama , Aprendizaje Profundo , Exosomas , Receptor ErbB-2 , Espectrometría Raman , Trastuzumab , Trastuzumab/uso terapéutico , Animales , Exosomas/química , Femenino , Ratones , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/orina , Espectrometría Raman/métodos , Humanos , Biomarcadores de Tumor/orina , Inmunoensayo/métodos , Antineoplásicos Inmunológicos/uso terapéutico
9.
Thromb Res ; 238: 172-183, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723522

RESUMEN

INTRODUCTION: Cancer cells induce hypercoagulability in the tumoral microenvironment by expressing Tissue Factor (TF). We aimed to study the impact of the procoagulant signature of cancer cells on the quality and structure of fibrin network. We also studied the impact of fibrin clot shield (FCS) on the efficiency of anticancer agents and the migration of cancer cells. MATERIALS AND METHODS: Pancreatic cancer cells BXPC3 and breast cancer cells MDA-MB231 and MCF7, were cultured in the presence of normal Platelet Poor Plasma (PPP), diluted 10 % in conditioning media. Their potential to induce thrombin generation and their fibrinolytic activity were assessed. The structure of fibrin network was analyzed with Scanning Electron Microscopy (SEM). Cancer cells' mobility with fibrin clot and their interactions with fibrin were observed. Cancer cells were treated with paclitaxel (PTX) or 4-hydroxy-tamoxifen (4OHTam) in the presence or absence of FCS. RESULTS: Cancer cells, in presence of PPP, induced fibrin network formation. High TF-expressing cancer cells (BXPC3 and MDA-MB23 cells), led to dense fibrin network with fine fibers. Low TF expressing cells MCF7 led to thick fibers. Exogenous TF enhanced the density of fibrin network formed by MCF7 cells. Cancer cells through their inherent profibrinolytic potential migrated within the fiber scaffold. The BXPC3 and MCF7 cells moved in clusters whereas the MDA-MB231 cells moved individually within the fibrin network. FCS decreased the efficiency of PTX and 4OHTam on the viability of cancer cells. CONCLUSIONS: The procoagulant signature of cancer cells is determinant for the quality and structure of fibrin network in the microenvironment. Original SEM images show the architecture of "bird's nest"-like fibrin network being in touch with the cell membranes and surrounding cancer cells. Fibrin network constructed by triggering thrombin generation by cancer cells, provides a scaffold for cell migration. Fibrin clot shields protect cancer cells against PTX and 4OHTam.


Asunto(s)
Antineoplásicos , Movimiento Celular , Fibrina , Microambiente Tumoral , Humanos , Movimiento Celular/efectos de los fármacos , Fibrina/metabolismo , Microambiente Tumoral/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Células MCF-7 , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Coagulación Sanguínea/efectos de los fármacos
10.
Aging (Albany NY) ; 16(9): 8279-8305, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38728370

RESUMEN

BACKGROUND: Cancer-associated fibroblasts (CAFs) are one of the most predominant cellular subpopulations in the tumor stroma and play an integral role in cancer occurrence and progression. However, the prognostic role of CAFs in breast cancer remains poorly understood. METHODS: We identified a number of CAF-related biomarkers in breast cancer by combining single-cell and bulk RNA-seq analyses. Based on univariate Cox regression as well as Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a novel CAF-associated prognostic model was developed. Breast cancer patients were grouped according to the median risk score and further analyzed for outcome, clinical characteristic, pathway activity, genomic feature, immune landscape, and drug sensitivity. RESULTS: A total of 341 CAF-related biomarkers were identified from single-cell and bulk RNA-seq analyses. We eventually screened eight candidate prognostic genes, including CERCAM, EMP1, SDC1, PRKG1, XG, TNN, WLS, and PDLIM4, and constructed the novel CAF-related prognostic model. Grouped by the median risk score, high-risk patients showed a significantly worse prognosis and exhibited distinct pathway activities such as uncontrolled cell cycle progression, angiogenesis, and activation of glycolysis. In addition, the combined risk score and tumor mutation burden significantly improved the ability to predict patient prognosis. Importantly, patients in the high-risk group had a higher infiltration of M2 macrophages and a lower infiltration of CD8+ T cells and activated NK cells. Finally, we calculated the IC50 for a range of anticancer drugs and personalized the treatment regimen for each patient. CONCLUSION: Integrating single-cell and bulk RNA-seq analyses, we identified a list of compositive CAF-associated biomarkers and developed a novel CAF-related prognostic model for breast cancer. This robust CAF-derived gene signature acts as an excellent predictor of patient outcomes and treatment responses in breast cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Fibroblastos Asociados al Cáncer , RNA-Seq , Análisis de la Célula Individual , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Fibroblastos Asociados al Cáncer/metabolismo , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genética , Transcriptoma , Perfilación de la Expresión Génica
11.
Biosens Bioelectron ; 258: 116373, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38729048

RESUMEN

Breast cancer is reported to be one of the most lethal cancers in women, and its multi-target detection can help improve the accuracy of diagnosis. In this work, a cluster regularly interspaced short palindromic repeats (CRISPR)-Cas13a/Cas12a-based system was established for the simultaneous fluorescence detection of breast cancer biomarkers circROBO1 and BRCA1. CRISPR-Cas13a and CRISPR-Cas12a were directly activated by their respective targets, resulting in the cleavage of short RNA and DNA reporters, respectively, thus the signals of 6-carboxyfluorescein (FAM) and 6-carboxy-xrhodamine (ROX) were restored. As the fluorescence intensities of FAM and ROX were dependent on the concentrations of circROBO1 and BRCA1, respectively, synchronous fluorescence scanning could achieve one-step detection of circROBO1 and BRCA1 with detection limits of 0.013 pM and 0.26 pM, respectively. The system was highly sensitive and specific, holding high diagnostic potential for the detection of clinical samples. Furthermore, the competing endogenous RNA mechanism between circROBO1 and BRCA1 was also explored, providing a reliable basis for the intrinsic regulatory mechanism of breast cancer.


Asunto(s)
Proteína BRCA1 , Biomarcadores de Tumor , Técnicas Biosensibles , Neoplasias de la Mama , Sistemas CRISPR-Cas , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico , Femenino , Biomarcadores de Tumor/genética , Técnicas Biosensibles/métodos , Proteína BRCA1/genética , ARN Circular/genética , Límite de Detección , Fluoresceínas/química , Proteínas Asociadas a CRISPR/genética
12.
Biosens Bioelectron ; 258: 116372, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38735081

RESUMEN

Epithelial-mesenchymal transition (EMT) promotes tumor cell infiltration and metastasis. Tracking the progression of EMT could potentially indicate early cancer metastasis. A key characteristic of EMT is the dynamic alteration in the molecular levels of E-cadherin and N-cadherin. Traditional assays have limited sensitivity and multiplexing capabilities, relying heavily on cell lysis. Here, we developed a multiplex electrochemical biosensor to concurrently track the upregulation of N-cadherin expression and reduction of E-cadherin in breast cancer cells undergoing EMT. Small-sized gold nanoparticles (Au NPs) tagged with redox probes (thionin or amino ferrocene) and bound to two types of antibodies were used as distinguishable signal tags. These tags specifically recognized E-cadherin and N-cadherin proteins on the tumor cell surface without cross-reactivity. The diphenylalanine dipeptide (FF)/chitosan (CS)/Au NPs (FF-CS@Au) composites with high surface area and good biocompatibility were used as the sensing platforms for efficiently fixing cells and recording the dynamic changes in electrochemical signals of surface proteins. The electrochemical immunosensor allowed for simultaneous monitoring of E- and N-cadherins on breast cancer cell surfaces in a single run, enabling tracking of the EMT dynamic process for up to 60 h. Furthermore, the electrochemical detection results are consistent with Western blot analysis, confirming the reliability of the methodology. This present work provides an effective, rapid, and low-cost approach for tracking the EMT process, as well as valuable insights into early tumor metastasis.


Asunto(s)
Técnicas Biosensibles , Neoplasias de la Mama , Técnicas Electroquímicas , Transición Epitelial-Mesenquimal , Oro , Nanopartículas del Metal , Humanos , Técnicas Biosensibles/métodos , Neoplasias de la Mama/patología , Oro/química , Femenino , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodos , Cadherinas , Línea Celular Tumoral , Inmunoensayo/métodos , Quitosano/química
13.
Genes Chromosomes Cancer ; 63(5): e23243, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38747337

RESUMEN

Breast cancer susceptibility 1/2 (BRCA1/2) genes play a crucial role in DNA damage repair, yet mutations in these genes increase the susceptibility to tumorigenesis. Exploiting the synthetic lethality mechanism between BRCA1/2 mutations and poly(ADP-ribose) polymerase (PARP) inhibition has led to the development and clinical approval of PARP inhibitor (PARPi), representing a milestone in targeted therapy for BRCA1/2 mutant tumors. This approach has paved the way for leveraging synthetic lethality in tumor treatment strategies. Despite the initial success of PARPis, resistance to these agents diminishes their efficacy in BRCA1/2-mutant tumors. Investigations into PARPi resistance have identified replication fork stability and homologous recombination repair as key factors sensitive to PARPis. Additionally, studies suggest that replication gaps may also confer sensitivity to PARPis. Moreover, emerging evidence indicates a correlation between PARPi resistance and cisplatin resistance, suggesting a potential overlap in the mechanisms underlying resistance to both agents. Given these findings, it is imperative to explore the interplay between replication gaps and PARPi resistance, particularly in the context of platinum resistance. Understanding the impact of replication gaps on PARPi resistance may offer insights into novel therapeutic strategies to overcome resistance mechanisms and enhance the efficacy of targeted therapies in BRCA1/2-mutant tumors.


Asunto(s)
Proteína BRCA1 , Proteína BRCA2 , Resistencia a Antineoplásicos , Mutación , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Resistencia a Antineoplásicos/genética , Proteína BRCA2/genética , Proteína BRCA1/genética , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Neoplasias/genética , Neoplasias/tratamiento farmacológico
14.
Psychooncology ; 33(5): e6342, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38747633

RESUMEN

OBJECTIVE: A mixed-methods systematic review to determine reported symptoms, concerns, and experiences of women living with and beyond breast cancer in Africa. METHODS: Literature searches were conducted in Medline, Embase, PsycINFO, Global Health, Web of Science, CINAHL, and the Cochrane Library. Quantitative and qualitative studies that comprised study populations of women with breast cancer from countries in Africa, detailing symptoms, concerns, and experiences of living with and beyond breast cancer were included. Inductive framework analysis was applied to organise existing literature with the Adversity, Restoration, and Compatibility framework and quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: In total, 48 studies were included, comprising quantitative (n = 24), qualitative (n = 23) and mixed method (n = 1) studies. Women reported multiple complex and burdensome symptoms at all stages of the breast cancer disease trajectory. Multiple pervasive factors influencing participants' experiences included a lack of cancer knowledge, being removed from decision-making, religion, and the presence and use of traditional medicines. Literature relating to benefit finding, understanding identity for the future, and broader perspectives of well-being was absent. CONCLUSIONS: This review contributes insights and mapping of symptoms, concerns, and experiences of women with breast cancer in Africa. There is a great necessity to increase an understanding of the needs and experiences of women with breast cancer in Africa following cancer treatment, stages of remission, and longer-term monitoring and follow-up. This is required to ensure access to prompt and timely clinical and individualized supportive care for women with breast cancer in Africa.


Asunto(s)
Neoplasias de la Mama , Humanos , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Femenino , África , Supervivientes de Cáncer/psicología , Investigación Cualitativa , Calidad de Vida/psicología , Conocimientos, Actitudes y Práctica en Salud
15.
J Cancer Res Clin Oncol ; 150(5): 259, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753081

RESUMEN

High mobility group AT-hook 2 (HMGA2) is a member of the non-histone chromosomal high mobility group (HMG) protein family, which participate in embryonic development and other biological processes. HMGA2 overexpression is associated with breast cancer (BC) cell growth, proliferation, metastasis, and drug resistance. Furthermore, HMGA2 expression is positively associated with poor prognosis of patients with BC, and inhibiting HMGA2 signaling can stimulate BC cell progression and metastasis. In this review, we focus on HMGA2 expression changes in BC tissues and multiple BC cell lines. Wnt/ß-catenin, STAT3, CNN6, and TRAIL-R2 proteins are upstream mediators of HMGA2 that can induce BC invasion and metastasis. Moreover, microRNAs (miRNAs) can suppress BC cell growth, invasion, and metastasis by inhibiting HMGA2 expression. Furthermore, long noncoding RNAs (LncRNAs) and circular RNAs (CircRNAs) mainly regulate HMGA2 mRNA and protein expression levels by sponging miRNAs, thereby promoting BC development. Additionally, certain small molecule inhibitors can suppress BC drug resistance by reducing HMGA2 expression. Finally, we summarize findings demonstrating that HMGA2 siRNA and HMGA2 siRNA-loaded nanoliposomes can suppress BC progression and metastasis.


Asunto(s)
Neoplasias de la Mama , Proteína HMGA2 , Humanos , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Resistencia a Antineoplásicos/genética
16.
JAMA Netw Open ; 7(5): e2411909, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38758553

RESUMEN

Importance: Oral endocrine treatments have been shown to be effective when carefully adhered to. However, in patients with early breast cancer, adherence challenges are notable, with 17% experiencing nonpersistence and 41% nonadherence at least once. Objective: To model the persistence of and adherence to oral anticancer treatment of a patient with localized breast cancer. Design, Setting, and Participants: This cohort study was conducted using anonymous reimbursement data belonging to French female patients with breast cancer, extracted from the French Health Insurance database from January 2013 to December 2018. Data analysis was conducted from January 2021 to May 2022. Main Outcomes and Measures: The main outcome was the detection of episodes of nonpersistence and nonadherence 6 months before they happened. Adherence was defined as the ratio between the time covered by a drug purchase and the time between 2 purchases; patients were considered nonadherent if the ratio of their next 3 purchases was less than 80%. Disparities in persistence and adherence based on criteria such as age, treatment type, and income were identified. Results: A total of 229 695 female patients (median [IQR] age, 63 [52-72] years) with localized breast cancer were included. A deep learning model based on a gated-recurrent unit architecture was used to detect episodes of nonpersistence or nonadherence. This model demonstrated an area under the receiving operating curve of 0.71 for persistence and 0.73 for adherence. Analyzing the Shapley Additive Explanations values also gave insights into the contribution of the different features over the model's decision. Patients older than 70 years, with past nonadherence, taking more than 1 treatment in the previous 3 months, and with low income had greater risk of episodes of nonpersistence. Age and past nonadherence, including regularity of past adherence, were also important features in the nonadherence model. Conclusions and Relevance: This cohort study found associations of patient age and past adherence with nonpersistence or nonadherence. It also suggested that regular intervals in treatment purchases enhanced adherence, in contrast to irregular purchasing patterns. This research offers valuable tools for improving persistence of and adherence to oral anticancer treatment among patients with early breast cancer.


Asunto(s)
Neoplasias de la Mama , Cumplimiento de la Medicación , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/psicología , Femenino , Cumplimiento de la Medicación/estadística & datos numéricos , Cumplimiento de la Medicación/psicología , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Francia , Antineoplásicos/uso terapéutico
17.
PLoS One ; 19(5): e0294923, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758814

RESUMEN

BACKGROUND: The workload of breast cancer pathological diagnosis is very heavy. The purpose of this study is to establish a nomogram model based on pathological images to predict the benign and malignant nature of breast diseases and to validate its predictive performance. METHODS: In retrospect, a total of 2,723 H&E-stained pathological images were collected from 1,474 patients at Qingdao Central Hospital between 2019 and 2022. The dataset consisted of 509 benign tumor images (adenosis and fibroadenoma) and 2,214 malignant tumor images (infiltrating ductal carcinoma). The images were divided into a training set (1,907) and a validation set (816). Python3.7 was used to extract the values of the R channel, G channel, B channel, and one-dimensional information entropy from all images. Multivariable logistic regression was used to select variables and establish the breast tissue pathological image prediction model. RESULTS: The R channel value, B channel value, and one-dimensional information entropy of the images were identified as independent predictive factors for the classification of benign and malignant pathological images (P < 0.05). The area under the curve (AUC) of the nomogram model in the training set was 0.889 (95% CI: 0.869, 0.909), and the AUC in the validation set was 0.838 (95% CI: 0.7980.877). The calibration curve results showed that the calibration curve of this nomogram model was close to the ideal curve. The decision curve results indicated that the predictive model curve had a high value for auxiliary diagnosis. CONCLUSION: The nomogram model for the prediction of benign and malignant breast diseases based on pathological images demonstrates good predictive performance. This model can assist in the diagnosis of breast tissue pathological images.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Persona de Mediana Edad , Adulto , Nomogramas , Fibroadenoma/patología , Fibroadenoma/diagnóstico por imagen , Fibroadenoma/diagnóstico , Estudios Retrospectivos , Mama/patología , Mama/diagnóstico por imagen , Anciano
18.
Life Sci Alliance ; 7(8)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38760173

RESUMEN

Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for understanding metastasis and potential therapies. We hypothesized that the unique F-actin binding and bundling protein SWAP-70 contributes importantly to metastasis. Orthotopic, ectopic, and short-term tail vein injection mouse breast and lung cancer models revealed a strong positive dependence of lung and bone metastasis on SWAP-70. Breast cancer cell growth, migration, adhesion, and invasion assays revealed SWAP-70's key role in these metastasis-related cell features and the requirement for SWAP-70 to bind F-actin. Biophysical experiments showed that tumor cell stiffness and deformability are negatively modulated by SWAP-70. Together, we present a hitherto undescribed, unique F-actin modulator as an important contributor to tumor metastasis.


Asunto(s)
Actinas , Neoplasias de la Mama , Neoplasias Pulmonares , Proteínas de Microfilamentos , Metástasis de la Neoplasia , Animales , Actinas/metabolismo , Ratones , Humanos , Femenino , Línea Celular Tumoral , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Movimiento Celular/genética , Citoesqueleto de Actina/metabolismo , Proliferación Celular/genética , Adhesión Celular/genética , Unión Proteica
20.
Bioprocess Biosyst Eng ; 47(6): 931-942, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38709274

RESUMEN

The conjugated silver nanoparticles using biomolecules have attracted great attention of researchers because physical dimensions and surface chemistry play important roles in toxicity and biocompatibility of AgNPs. Hence, in the current study, synthesis of bio-conjugated AgNPs with protein protease inhibitor (PI) isolated from Streptomyces spp. is reported. UV-visible spectra of PI and AgNPs showed stronger peaks at 280 and 405 nm, confirming the synthesis of conjugated AgNPs-PI. TEM and SEM images of AgNPs-PI showed spherical-shaped nanoparticles with a slight increase in particle size and thin amorphous layer around the surface of silver nanomaterial. Circular dichroism, FT-IR and fluorescence spectral studies confirmed AgNPs-PI conjugation. Conjugated AgNPs-PI showed excellent anticancer potential than AgNPs and protease inhibitor separately on human breast MCF-7 and prostate PC-3 cell lines. The findings revealed that surface modification of AgNPs with protein protease inhibitor stabilised the nanomaterial and increased its anticancer activity.


Asunto(s)
Antineoplásicos , Nanopartículas del Metal , Plata , Humanos , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Antineoplásicos/farmacología , Antineoplásicos/química , Células MCF-7 , Células PC-3 , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral
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